During the COVID-19 pandemic, immunisation of infants has been a highly contentious and confusing issue. From initial advice that children would be less severely affected, to the FDA’s emergency-use-authorisation of the BNT163b3 and the mRNA-1273 vaccines in June 2022, public health messaging has been mixed. Powerful rhetoric surrounding vaccinating children has also had a worrying effect on routine immunisations. However, a recent study published in Science Translational Medicine by researchers in the US suggests that, following “safe and immunogenic” vaccination, antibodies against variants of concern (VOC), as well as T-cell responses, “persisted for 12 months”.
The study in context
SARS-C0V-2 has infected “close to 600 million” and caused “more than 6 million deaths”, the study reports. Although vaccines were developed in record time, we continue to engage with variants and widespread infection, dangerously coinciding with an increase in other disease infections. Furthermore, the authors note that vaccination has not been widely accepted, for a variety of reasons.
Children younger than 5 years old were originally excluded from vaccination due to “stringent age de-escalation clinical trial protocols” and initial data about infection. However, COVID-19 can cause “severe disease” and death in children, and the emergence of the “more transmissible” variants increased disease incidence in the paediatric population. Neonates were “one of the most affected age groups”. Despite “controversy”, recent data demonstrate the “immunogenicity and efficacy of mRNA SARS-CoV-2 vaccines” at lower doses.
As these doses are scaled proportionately to those of adults, and immune responses have been observed to decline over time in adults, it is important to “determine whether vaccine-induced antibody responses are durable and of sufficient breadth to protect against infection” with new VOCs.
COVID-19 in rhesus macaques
The research involved two groups of 2-month of rhesus macaques (RMs), at weeks 0 and 4. To establish efficacy at one year after initial immunisation, the 2 groups and an added control group of age-matched non-immunised RMs were “exposed to a high-dose heterologous challenge” with the ‘Delta’ variant.
7 of the 8 control RMs “exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract”. By contrast, the vaccinated RMs had “faster viral clearance” and “mild to no pneumonia”.
Limitations of the study include “relatively small group sizes” and the “short follow-up period after SARS-CoV-2 challenge”. Furthermore, the authors acknowledge that “infant RM studies cannot replace human infant vaccine safety and dosing studies”. However, the similarities in “infant physiology and immune development” support a reasonable comparison.
What does this mean?
The authors hope that their results will provide a “valuable contribution to efforts to alleviate” parental concerns. The findings add to current data to “provide strong support to initiate SARS-CoV-2 vaccination in infancy and incorporate new SARS-CoV-2 vaccines into the global routine paediatric vaccine schedules to curb the SARS-CoV-2 pandemic”.
On 1st December 2022 Pfizer and Valneva reported antibody persistence data 6 months after the completion of a vaccination schedule with their Lyme disease vaccine candidate, VLA15. This was reported in both children and adults, the first time that antibody resistance data are reported in paediatric populations for this vaccine candidate.
Moving through the Phases
As we reported earlier this year, Phase II in April 2022 produced “positive immunogenicity and safety data”. As a result, the investigations continued, to evaluate the persistence of antibodies 6 months after the study of a Month 0-2-6 and Month 0-6 vaccination schedule. This was done in healthy adults and paediatric participants.
Data were collected in 96 health adults and 81 paediatric participants (5-17 years of age) for the schedule involving vaccination at months 0-2-6, and 84 healthy adults and 78 paediatric patients for the month 0-6 schedule.
Although antibodies did decline over time, they remained “above baseline”, confirming persistence 6 months after the completion of both schedules. Antibody levels generally remained higher after the 3-dose schedule, compared to the 2-dose schedule. The statement also indicated that “no vaccine-related serious adverse events (SAEs) and no safety concerns” were observed in the follow up.
Several months ago, Pfizer and Valneva initiated a Phase III study, VALOR. Enrolment is taking place across Europe and the US, with up to 6,000 participants over the age of 5 expected to receive 3 doses of VLA15 or a saline placebo, followed by a booster dose.
Validation of the vaccine
Dr Juan Carlos Jaramillo, CMO at Valneva, is “pleased with these antibody persistence data”. They “further validate” the 3-dose vaccination strategy for the Phase III study and the “acceptable safety and tolerability profiles of our vaccine candidate”.
“Lyme disease continues to spread, representing a high unmet medical need that impacts the lives of many in the Northern Hemisphere, and each new report of positive data takes us a step closer to potentially bringing this vaccine to both adults and children who could benefit from it.”
Dr Annaliesa Anderson, SVP and CSO of Vaccine Research and Development at Pfizer agreed, suggesting that “rates of Lyme disease continue to increase globally”.
“These six-month antibody persistence data are encouraging, and we hope that the data generated from the Phase III studies will further support the positive evidence for VLA15 to date.”
To hear from speakers from both Pfizer and Valneva at the World Vaccine Congress in Washington 2023 get your tickets now.
During a bilateral meeting between Dr Ahmed Ogwell Ouma, Acting Director General of Africa CDC, and Korea Disease Control and Prevention Agency (KDCA) Commissioner PECK Kyong Ran it was announced that the KDCA will donate a batch of the mpox vaccine to Africa. The meeting took place at the 7th Global Health Security Agenda Ministerial Meeting held in the Seoul, the Republic of Korea.
Mpox in Africa
The African CDC emphasises that mpox has been “endemic for decades in some African countries”. However, with recent outbreaks in other countries, the WHO declared it a PHEIC in July 2022. The statement from CDC suggests that this decision “sparked a more coordinated international response”, yet Africa “has yet to receive vaccines”. As we noted in an earlier article, this is a frustration for health leaders in Africa, who called for attention at the “source”.
Collaboration with Korea
Dr Ahmed Ogwell Ouma welcomed the collaboration behind the donation. It comes after an agreement signed in April 2022 through a MoU between Africa CDC and KDCA.
“We appreciate this gesture and assure that these mpox vaccines will be prioritised in the most affected African Union Member States.”
The MoU reportedly established a “joint plan of action” to promote cooperation in “areas of mutual interest”. As we have previously noted, Africa produces a very small percentage of the vaccines it requires. This is hopefully changing through knowledge and technology transfers, which will enable the continent to be less dependent on wealthier areas for vaccines. This inevitably and unfortunately results in vaccine nationalism and hoarding, rather than equitable access.
The announcement of this donation comes days after the Republic of Korea was congratulated on obtaining ML4 in the WHO assessment of its Ministry of Food and Drug Safety.
To hear more from experts on the future of vaccines and viruses in Africa at the World Vaccine Congress in Washington, April 2022, get your tickets today.
In November 2022 HDT Bio Corp. and the University of Texas Medical Branch (UTMB) revealed that they had been awarded a project agreement worth up to $87.4 million. The US Department of Defence’s (DOD) Joint Programme Executive Office for Chemical, Biological, Radiological, and Nuclear Defence (JPEO-CBRND) and BARDA have awarded this for the “development of a vaccine technology against advanced and emerging viral threats”. The two viruses that will be targeted specifically are Crimean-Congo haemorrhagic fever virus (CCHFV) and Nipah virus (NiV) for their “significance to military personnel”.
Phase I funding
UTMB has reportedly partnered with HDT Bio to “leverage the company’s self-amplifying RNA (saRNA) vaccine platform technology and proprietary LION delivery system”. The project will cover the development of vaccine candidates, HDT-321 (CCHFV) and HDT-331 (NiV) through Phase I clinical trials. HDT Bio will receive $49 million as a “sub-performer” for the development of these vaccine candidates.
HDT Bio CEO Steve Reed is “grateful” to DOD and HHS for their support.
“We look forward to working with our partners and the MCDC to protect our military personnel and the American people as a whole from biological threats”.
Two zoonotic threats
The CDC states that CCHF is caused by infection with a tick-borne virus (Nairovirus) of the Bunyaviridae family. It was first identified in the Crimea in 1944 and later recognised in 1969 as the cause of illness in the Congo. It is found across Europe, Africa, the Middle East, and the Indian subcontinent. The death rate ranges from 9% to 50%.
NiV is associated with mild illness to encephalitis to death. Fruit bats are the animal reservoir. The CDC suggests that outbreaks occur “almost annually” in parts of Asia. HDT Bio indicates that death rates can be up to 61%.
“Both of the viruses contain multiple antigen targets that have previously been associated with protective immunity, which affords an opportunity to design and develop vaccines against more than one vulnerability using a multi-antigen approach.”
Shifting vaccination approaches
UTMB Co-PI Dr Robert Cross suggests that the COVID-19 pandemic has “clearly demonstrated” a “shift” in vaccination approaches. RNA-based vaccines were “instrumental” in this pandemic and can be applied to “other high priority viruses with pandemic potential”. For HDT Bio’s PI, Dr Jesse Erasmus, “next-generation technologies are urgently needed” to fight diseases in a “safe and tolerable manner”.
“With the recent emergency use authorisation of our LION/saRNA platform for COVID-19, the first saRNA technology to reach this milestone, we are poised to unlock this modality’s dose-sparing capacity to achieve multi-target protective immunity in humans.”
1st December 2022 is World AIDS Day, with global communities observing it under the theme “equalise”. This year, the WHO is calling on “leaders and citizens” to identify and address the inequalities that challenge progress in “attaining the global goal to end AIDS by 2030”. The theme highlights the importance of ensuring that essential HIV services reach the most in need and at risk. This includes children.
COVID-19 forced us back
Earlier in the year we reported on the UNAIDS report that suggested that the “global AIDS response is under threat”. UNAIDS Executive Director Winnie Byanyima suggested that during 2021 a life was lost to AIDS every minute. Furthermore, the growth in the number of people with access to treatment was slower than in previous years.
The WHO’s most recent statistics reinforce the urgency of UNAIDS’ report:
Of the 38 million people living with HIV, 5.9 million people who know they have HIV are not receiving treatment.
A further 4 million people living with HIV have not yet been diagnosed.
While 76% of adults overall were receiving antiretroviral treatment that help them lead normal and healthy lives, only 52% of children living with HIV were accessing this treatment globally in 2021.
70% of new HIV infections are among people who are marginalized and often criminalized.
While transmission has declined overall in Africa, there has been no significant decline among men who have sex with men – a key population group – in the past 10 years.
Mpox makes matters worse
Current WHO data shows that the percentage of people confirmed to have mpox and be living with HIV is high: 52%. Data reported to WHO suggest that people with mpox with untreated HIV “appear to be at risk for more severe disease than people without HIV”.
“The current response to mpox shows that transmission can move quickly in sexual networks and within marginalized populations. But it can also be prevented with community-led responses and open attitudes to address stigma, and health and well-being can be improved, and lives can be saved.”
Goals for the future
With the shared goal of ending AIDS as a public health threat by 2030, the clock is ticking on collaborative action. Thus, the UN describes the impetus for “all of us to work for the proven practical actions needed to address inequalities and help end AIDS”.
WHO Director General Dr Tedros Adhanom Ghebreyesus emphasised the importance of “global solidarity and bold leadership” to ensure that “everyone receives the care they need”. For Dr Meg Doherty, WHO Director of the HIV, Hepatitis, and STI programmes, access should not be a barrier to “health for all”.
“In order to end AIDS, we need to end new infections among children, end lack of treatment access to them, and end structural barriers and stigma and discrimination towards key populations as soon as possible.”
Vaccines on the scene
During the World Vaccine Congress in Europe in October 2022, we spoke to Dr Christian Brander of Aelix Therapeutics, to learn more about the possibility of vaccines for HIV. You can watch his interview here or click here to read more about the results of trials to this end.
For updates on HIV vaccines at the World Vaccine Congress in Washington 2023, get your tickets now.
In November 2022 the White House issued a statement indicating the intention of the Biden-Harris Administration to continue to “prioritise global health security” as part of wider efforts in “national biodefence”. Highlighting ongoing outbreaks alongside the continued threat of COVID-19, the statement emphasised the importance of preparedness for infectious diseases and how “global health systems remain ill-equipped to identify and contain these threats”. With “new actions” the Administration hopes to accelerate the “National Biodefence Strategy and Implementation Plan for Countering Biological Threats, Enhancing Pandemic Preparedness, and Achieving Global Health Security (Strategy)”.
Constant and consistent threats
The statement began with the acknowledgement that the world is continuing to fight COVID-19. This comes just weeks after Biden’s statement that the pandemic was “over”, perhaps inadvertent, which caused ripples in the pharmaceutical industry. It continued by referring to the suffering caused by Mpox, recently renamed, and the Ebola outbreak in Uganda. These are “two of the most recent examples of how the risks and impact of emerging infectious diseases are increasing daily”.
The Administration describes a “bold and ambitious roadmap” that will “protect American lives and livelihoods” and offer protection against infectious disease threats, “whether naturally occurring, accidental, or deliberate”. This qualification is perhaps a recognition of the heated debate over the origins of COVID-19.
Through secure partnerships, the statement highlights the importance of stopping disease threats “at their source”. As we saw recently in the mpox outbreak, this is something we continue to fail to do, prioritising apparent national interests over obvious international health.
“The United States is committed to directly supporting at least 50 countries, by 2050, to strengthen and achieve regional, national, and local capacity in five critical areas to prevent, detect, and respond to infectious disease threats.”
How will this happen? The White House sets out several specific goals as follows:
Expand and strengthen bilateral partnerships with at least 25 countries to develop measurable capacity to prevent, detect, and rapidly respond to epidemic and pandemic threats.
Build and expand regional partnerships in Africa, Asia, and Latin America on infectious disease surveillance and early warning systems, biosafety and biosecurity, strengthening emergency operations centres, training and supporting health workers, investing in community and national leadership for global health security, and legal preparedness. These partnerships also include the multisectoral African Partner Outbreak Response Alliance (APORA) and joint efforts between the US Indo-Pacific Command and Australian Defence Force.
Leverage bilateral US global health security programmes alongside investments from the newly established Pandemic Fund at the World Bank to achieve additional measurable results at the national, regional, and global level, and spur new resource mobilisation for pandemic preparedness and response.
Support implementation of the third edition of the WHO’s Joint External Evaluation (JEE). The CDC will provide technical experts to support 10 countries’ JEEs, assisting in gap assessments and developing recommendations to address them.
Global example and encouragement
The statement suggests that global health security “cannot be achieved alone”. Thus, in addition to “expanding bilateral partnerships”, the US will “utilise its unparalleled catalytic leadership to unlock more commitments” to “bolster support”. The following actions are set out in the statement:
Strengthen and support the extension of the multilateral GHSA beyond 2023, as a forum for working across countries, regions, sectors (including non-governmental) to provide technical assistance and share best practices and measure and hold global partners accountable for progress. This week, the United States joined other multi-sectoral delegations in committing to and calling for new actions during the 7th GHSA Ministerial in Seoul, Republic of Korea.
Strengthen the new Pandemic Fund at the World Bank as a founding Board Member to deliver early impact for those countries and regions most in need, including supporting them to strengthen and achieve measurable capacity in critical areas.
Accelerate G7 commitments made by the United States and its close allies in 2021 and 2022, including meeting milestones of the G7 Pact for Pandemic Readiness towards assisting at least 100 countries, and collaborating with Japan’s G7 Presidency to expand health security investments, bolster medical countermeasure development and delivery, and grow pandemic preparedness and response financing. This G7 commitment matches the United States’ own 50 country target commitment and aligns with the target of the GHSA 2024 initiative.
Support the planned Global Health Security Coordinating Office being established by Republic of Korea and expected to launch in 2023, including strengthening coordination and collaboration with the U.S. Centers for Disease Control & Prevention’s new East Asia regional office.
As well as global concerns, the White House will continue to promote national pandemic preparedness within the country and its region, working with “partners in the Western Hemisphere”. Working regionally, in North and South America, the Administration will:
Commit, working with the WHO and the Pan American Health Organisation (PAHO), to initiate and conduct a renewed external evaluation of U.S. health security and pandemic preparedness capacity by the end of 2024, in line with strong U.S. commitment to the International Health Regulations and using the new Joint External Evaluation (JEE) 3.0 Tool.
As tasked in NSM-15, revise the U.S. Global Health Security Strategy to incorporate lessons from the COVID-19 pandemic and further outline the Administration’s international strategy and support for achieving a stronger, more secure global health security architecture with equity at the centre.
Work collaboratively with Canada and Mexico under the North American Leaders’ Summit (NALS) to revise the North American Plan for Animal and Pandemic Influenza (NAPAPI) based on lesson learned from COVID-19. The three countries plan on developing and launching a new NAPAPI at the 11th NALS as a key cross-sectoral, flexible, and scalable trilateral framework for strengthening regional preparedness and response to a broader range of health security threats that includes influenza and beyond.
Strengthen regional engagement, including establishing a new U.S. Centers for Disease Control & Prevention regional office in Panama City, Panama, serving Central America and the Caribbean.
Establish and support, in collaboration with PAHO and the InterAmerican Development Bank, the Economic and Health Dialogue of the Americas (EHA), which aims to convene Ministries of Health, Finance, Economy, and Foreign Affairs of countries in the Western Hemisphere to jointly address the economic repercussions of COVID-19 and strengthen regional pandemic preparedness.
“Investing billions of dollars today in global health security can save trillions of dollars and millions of lives.”
The Biden-Harris Administration thus “urges” Congress to “fully meet this unique moment in history”. With the opportunity to provide the additional resources to “sustain and accelerate progress” for the partnerships, the Administration hopes that Congress will respond favourably. To demonstrate the effect of such investments, the Administration also released its annual report to detail “key outcomes”.
“In publishing these significant and measurable results, the United States continues to model transparency and accountability for its health security investments with global partners and calls on countries and non-governmental organisations to do the same.”
“The results are clear: Investing in preparedness and prevention saves lives and yields tangible results, including helping to rapidly address outbreaks of Ebola, yellow fever, Lassa fever, polio, influenza, and many others.”
In November 2022 PharmaJet announced that it had received an NIH grant of $800,000 towards their Phase II investigation of the immunogenicity of intradermal administration of a human papillomavirus (HPV) vaccine. Using PharmaJet’s Tropis intradermal (ID) needle-free injection system (NFIS), the study will compare this method against traditional needle and syringe administration.
HPV in Indonesia
The study takes place in Indonesia, in collaboration with Padjadjaran University. The WHO suggests that more than 95% of cervical cancer is due to HPV. In Indonesia, cervical cancer is the 2nd leading cause of female cancer, according to HPV Information Centre. An estimated 36,600 new cervical cancer cases are diagnosed each year in Indonesia.
Of the 342,000 deaths believed to be caused by cervical cancer in 2020, roughly 90% occurred in low- and middle-income countries. PharmaJet suggests that this is due to “limited access to preventative measures” and late identification. Furthermore, treatment options may be limited in these areas.
The study will aim to recruit around 900 girls, between the ages of 9 and 14, at the start of 2023. This comes after preliminary studies have evaluated intradermal delivery for HPV vaccines. Intradermal administration is already “widely used” for polio vaccine delivery. It has been found to be “safe, effective, and immunogenic”.
PharmaJet identifies its mission as to “enable greater access to life improving pharmaceuticals.
“We are committed to helping our partners realise their research and commercialisation goals while making an impact on public health.”
Vice President of Clinical and Regulatory Affairs, Dr Erin Spiegel, is “pleased to receive this grant from the NIH”.
“Intradermal administration of vaccines can provide benefits for low resource settings including lower costs, increased coverage, and increased acceptability.”
Dr Spiegel outlined some of the benefits of PharmaJet’s system in our recent interview at the World Vaccine Congress in Europe 2022. To learn more, watch it here.
The WHO announced in November that the Ministry of Food and Drug Safety (MFDS), Republic of Korea, achieved maturity level 4 (ML4) in its ranking of regulatory authorities for medical products. This is the highest level. Out of 33 countries assessed, only the Republic of Korea was listed as securing this level of regulatory recognition.
WHO described the occasion as an “important milestone” for both the Republic of Korea and the world. It signifies that the MFDS is “operating at an advanced level of performance with continuous improvement”. Dr Zsuzsanna Jakab, WHO Deputy Director-General and Office-in Charge of the Western Pacific Regional Office, received the “great news”, remarking that the Republic of Korea is the “first country in the world to be assessed by WHO and recognised as having achieved the highest level for both vaccines and medicines regulation”.
Dr Oh Yu-Kyoung, Minister, MFDS, stated that it was a “great honour” to receive confirmation of the WHO’s recognition.
“The Ministry of Food and Drug Safety will continue to strengthen close collaborations with the WHO in sharing its experience of establishing advanced level of regulatory system and supplying safe and high-quality medicines and vaccines.”
The rest of the world
WHO suggests that “only about 30%” of the regulatory authorities across the globe have the “capacity to ensure” that health products are “produced to required standards, work as intended, and do not harm patients”.
The benchmarking efforts shine a spotlight on advanced regulatory authorities to set an example for others that “lack the resources to perform all necessary regulatory functions”. Based on the “Global Benchmarking Tool” the assessment revealed that 11 other countries have attained ML3, and Singapore has attained ML4 in medicines regulation.
“Countries with ML3 and ML4 are eligible to become a WHO listed authority (WLA), following a further performance evaluation.”
The WLA is a scheme for “designating regulatory authorities” as reference points for others to support them in decision-making.
We will hear more on the various regulatory processes involved in vaccine development and distribution at the World Vaccine Congress in Washington next year. To join us, get your tickets now.
In November 2022 CEPI announced an investment of U$5.7 million towards the development of a second-generation molecular clamp vaccine platform at the University of Queensland (UQ). This platform will be aimed at “combatting the next Disease X”. The funds will contribute to the testing of “promising technology” for use in a global response to future disease outbreaks.
Molecular clamp technology works by “locking viral proteins” into a shape that facilitates “optimal immune response”. It requires the sequence of the viral protein, determined from its genome, which is then “coupled with an optimised ‘clamp’ sequence”. CEPI describes how the “resulting synthetic antigen” can be purified and “rapidly manufactured” into a vaccine.
The team at UQ has spent months re-engineering a previous molecular clamp technology and demonstrating its safety in lab tests.
Previous clamp attempts
In January 2019 CEPI entered a partnering agreement with UQ to develop a molecular clamp vaccine platform. With the arrival of SARS-CoV-2 in late 2019, CEPI and UQ began work on vaccines against the virus. In July 2020 the team had started clinical testing of a vaccine candidate. Unfortunately, scientists at UQ discovered that a “constituent of the vaccine” also resulted in “diagnostic interference with some HIV tests”. Thus, further development was halted.
“Nevertheless, CEPI believed that the concepts underlying UQ’s molecular clamp technology showed great promise.”
Vaccine equity through technology
Committed to equitable access, CEPI has ensured that UQ agrees to make vaccine candidates available in outbreak situations to “populations at risk”. Jane Halton, Chair of CEPI, described the important role that the Australian Government and R&D sector are playing in “bolstering future pandemic preparedness”. Dr Melanie Saville, Executive Director of Vaccine R&D at CEPI identified the “true grit” and the “power of the scientific process” at play in this research.
“This second-generation molecular clamp vaccine technology could provide the world with an invaluable tool to rapidly respond to future pandemic threats.”
She hopes to “mitigate the devastating” effects of future pandemics with this collaboration. The leader of UQ’s Rapid Response Vaccine Pipeline is Associate Professor Keith Chappell. He displayed gratitude for the “continuing support from CEPI” as well as the governments and “philanthropic partners”.
“Pre-clinical testing had shown the ‘Clamp2’ platform was meeting all expectations, producing stabilised antigens, and inducing strong neutralising immune responses”.
To hear more about global preparations for Disease X at the World Vaccine Congress in Washington in April, get your tickets now.
The WHO announced in November 2022 that, after “consultations with global experts”, it will begin using a preferred term “mpox” for monkeypox. While the word monkeypox is “phased out” both terms will be used simultaneously for one year. This move is made in attempts to tackle “racist and stigmatising language” surrounding the recent outbreak of the disease.
What’s in a name?
The International Classification of Diseases (ICD) and the WHO Family of International Health Relate Classifications take charge of assigning names to new and existing diseases “through a consultative process”. This includes WHO Member States. Following the process, WHO held consultations with a range of groups, from experts to the general public. Consequently, WHO Director-General Dr Tedros Adhanom Ghebreyesus recommended the following:
Adoption of the new synonym mpox in English for the disease.
Mpox will become a preferred term, replacing monkeypox, after a transition period of one year. This serves to mitigate the concerns raised by experts about confusion caused by a name change in the midst of a global outbreak. It also gives time to complete the ICD update process and to update WHO publications.
The synonym mpox will be included in the ICD-10 online in the coming days. It will be a part of the official 2023 release of ICD-11, which is the current global standard for health data, clinical documentation and statistical aggregation.
The term “monkeypox” will remain a searchable term in ICD, to match historic information.
Considerations for these recommendations included “rationale, scientific appropriateness, extent of current usage, pronounceability, usability in different languages, absence of geographical or zoological references, and the ease of retrieval of historical scientific information”. The process was accelerated through standard steps.
The previous name
Human monkeypox was named in 1970, before the WHO published its “best practices in naming diseases” in 2015. The virus that causes the disease was identified in captive monkeys in 1958. In this publication, new disease names should be assigned with the aim to minimise “unnecessary negative impact” on “trade, travel, tourism or animal welfare, and avoid causing offence to any cultural, social, national, regional, professional, or ethnic groups”.
In August 2022, experts convened by WHO agreed to align the names of the individual “clades” of mpox with best practices. The formerly named Congo Basin clade became Clade 1, and the former West African clade became Clade 2.
For a range of discussions on mpox and public health concerns at the World Vaccine Congress in Washington next year, get your tickets now.
With the World Vaccine and Immunotherapy Congress kicking off in San Diego today we are delighted to share another exclusive interview with the community. We were lucky to hear from Dr Ariel Weinberger, founder and CEO of Autonomous Therapeutics since 2017. Autonomous is a “scientist-led company” working on the development of the “first variant-proof RNA therapeutics”. Looking ahead, the team is hoping to create “effective countermeasures” before the next pandemic.
The consequences of the mRNA revolution for therapeutics
As mRNA entered its heyday during the COVID-19 pandemic, scientists and industry leaders rushed to make the most of the emerging potential. We asked Dr Weinberger about how the storming success of the mRNA vaccines might influence therapeutic interventions, and what challenges might be associated with an mRNA-based future. He began by suggesting that the “comparison to mRNA vaccines highlights a number of the challenges faced by mRNA therapeutics”.
Vaccines vs therapeutics
“If you think about vaccines, a core idea is to harness the body’s adaptive immune system for both signal amplification and memory. So, a relatively small vaccine dose can, in principle, confer immunity for years—although, of course, that hasn’t yet been the outcome for COVID-19 vaccines.”
Dr Weinberger explained that “the barriers for mRNA therapeutics arise, in large part, because they cannot leverage the body’s adaptive immune system for amplification and persistence”.
“As a result, you often need to administer far higher therapeutic doses—a recent review noted that mRNA doses are often 100 to 1000-fold higher for therapeutics than vaccines. And you may need to administer those doses repeatedly, because current RNA technologies can degrade in hours to days. And there’s another barrier: current RNAs, including those delivered in lipid nanoparticles, can lead to substantial immunogenicity. This may provide an adjuvant advantage for vaccines, but it’s unfortunately an additional way to accelerate the loss of therapeutic RNA.”
Despite the challenges, Dr. Weinberger believes that mRNA therapeutics are likely to succeed.
“It’s worth noting that these challenges were previously overcome for siRNA therapeutics. The drug that comes to mind is Alnylam’s Onpattro. So, there’s a clear precedent for believing that we’ll find solutions for mRNA therapeutics, too.”
We then asked Dr Weinberger about the opportunities for mRNA therapeutics, and how he understands a next-generation approach will enable us to use them. In his answer he highlighted the importance of “novel technologies” to “tackle the barriers” he explored above. He is particularly excited to encounter some of these next-generation mRNA technologies at the Congress (he gets brownie points for being enthusiastic about other people’s sessions)!
For example, self-amplifying RNAs are being developed to directly amplify RNA in vivo, circular RNAs are being developed to enhance RNA persistence, and novel transcription and purification strategies are being developed to minimise inherent RNA immunogenicity. But I also think that some of the greatest opportunities of mRNA technologies may be paradigmatically different. If you think about it, current mRNA therapies are often focused on producing proteins in vivo. I think a fair question is: “why don’t you just deliver the protein directly’? We may not like asking that question in the mRNA field, but we clearly have to—since some of our competitors are in the protein field.
Asking the right questions
Once this question has been asked, Dr Weinberger has another for his colleagues: “what can we do with mRNA therapeutics that we can’t do with proteins?” He suggests that “if we can answer that question, we have a potential path to developing next-generation drugs that weren’t previously possible”.
“Here are some examples. I think about proteins that are extremely difficult to produce, purify, or effectively deliver—for example, transmembrane proteins. Or therapeutic proteins that you don’t want to express constitutively and systemically, but that are life-saving in certain contexts. Ultimately, I think about how mRNA could be used as a circuit board to precisely control therapeutic protein production both temporally and spatially.
For Dr Weinberger, mRNA “2.0” moves from “plug-and-play production to plug-and-play control”.
“There are a few companies already thinking about this in the cancer context—imagine if we could localise chemotherapies or immunotherapies—and I think there will be more from cancers to autoimmune diseases.”
Autonomous’ pandemic protection against the unknown
We identified on Autonomous’ website the intention to develop countermeasures “before” the next pandemic. So, naturally, we were curious to understand how this works. First and foremost, Dr Weinberger was keen to emphasise that they’re not trying to “predict the future”.
“Before I started Autonomous, I spent years mathematically modelling the evolution and spread of pandemic viruses. And the lesson I kept learning is that you can’t predict a stochastic process with scores of unmeasurable parameters and “heavy” tails to the level of detail that you need to develop an effective precision therapy in advance. And even if we could know the random genotype of a future viral variant, we wouldn’t have a way to map its pandemic potential. Some have proposed using new AI approaches to solve these problems—but the pandemic prediction problem is likely a lot less tractable (and deterministic) than problems in, say, computer vision where AI has changed the world.”
For Dr Weinberger, the solution is “to develop broad-spectrum or variant-proof countermeasures that can control whatever viral variant ultimately emerges—even if the precise genomic confirmation of that variant is frankly unpredictable months to years in advance”.
How can we do this?
“One option is to target the part of the system that doesn’t change from virus to virus: the host. And we’ve seen a ton of recent interest in host-directed therapeutics; I think it’s an extremely promising avenue. The concern has always been that targeting the host means targeting the host, and raises the spectre of toxicity”.
“The other approach is to find the kernels of viral genomes or proteins that don’t change from virus to virus. These conserved viral elements are not likely to be in the Spike or receptor-binding proteins of a virus that vaccines generally target—those proteins are under too much diversifying selection from the immune system. In fact, the conserved regions that we want to target are often the regions that are the least well-suited for vaccine and antibody approaches. But these regions can be targeted using RNA technologies.”
Although there is “too much viral genomic diversity” for us to be able to develop a single virus-targeted drug, Dr Weinberger suggests that we “find elements that are conserved within a viral genus or species”.
“For example, we can find targets that are conserved across all the variants of SARS-CoV-2 or across all influenza variants. And then we have the possibility of developing countermeasures that don’t lose efficacy every 6 months—and that can be effectively administered for lifetimes. More broadly, we have the possibility of pre-developing an armamentarium of pan-variant countermeasures for each major viral family. That’s what Autonomous uses RNA to do.”
As terribly vulgar as it is to discuss money, in some situations curiosity just gets the better of us. Particularly in a post-pandemic world, we wondered what the funding landscape looks like for early-stage companies. Dr Weinberger thinks that “substantial funding will remain in the space, at least in the near term”. Although there is “always some reversion”, as the money moves where the “next hottest thing” is, he believes that “financial incentives are hard to ignore for an investor”.
“You’re talking about $75B that’s likely to be grossed for COVID this year alone by just two companies (and we keep hearing that the pandemic is over). At the same time, these numbers were clear before the pandemic. The market sizes for viral pathogens with pandemic potential are (unfortunately) massive. And there were already blockbuster returns for earlier antivirals and vaccines—from HIV and HCV to HPV.”
“I think that some of the historical shortfalls for antiviral and vaccine funding have also been on us: the companies. We haven’t always been developing new classes of approaches that offer major benefits over state-of-the-art strategies. How many similar monoclonal antibody or Spike vaccine approaches can we keep funding? More fundamentally, some of the issues have been at the Government and academic level. If we keep funding the same sorts of basic science studies, we’ll get more of the same translational products, and less of the same investment funding.”
“My view is that new classes of drugs and vaccines for major market indications will always have substantial investor interest—and that’ll especially be the case in the ID space after COVID. It’s just that you have established biopharma companies that have already developed and clinically tested existing products. The bar is high: you have to disrupt and supplant these existing approaches to enable the kinds of potential returns that would really excite investors.”
Eventually our conversation turned to the future, and what we should be most worried about, or invested in. As Dr Weinberger specialises in viruses, he believes, for “good reason” that these the “critical global health threats”. Previously, he suggested that “we can’t predict the next outcome of a random process”. We don’t know if the next pandemic will be “another flu, COVID, or an entirely different pathogen”.
“I think that we can fairly assume that there are going to be more viral pandemics – we’re still in one. And many of the pandemic strains that emerge will likely be close relatives (i.e. variants) of viruses that have previously infected large numbers of humans. After all, these viruses have already crossed the major evolutionary barrier: transmission across humans. To me, the critical threat is that the next pandemic variant is again untreatable or is resistant to all approved therapeutics and vaccines. In other words, after years of COVID and millions of deaths, we could be back in March 2020 all over again.”
“Sure, new platform technologies (including mRNA) could speed up response times—so maybe we’ll have an authorised vaccine or monoclonal antibody in 6 months. But we know that’s six months too late and that it’s fundamentally impossible to develop, clinically test, and manufacture a new countermeasure faster than a pandemic virus can spread.”
So, fail to prepare and prepare to fail. Thankfully, Dr Weinberger and his colleagues are working to prepare for future threats. It’s encouraging to hear that some of hard lessons from COVID-19 have been taken on board.
“We were based in New York City in March 2020. Being in that environment is something that you never forget. People felt helpless and knew that there were few medical countermeasures for them or their families if an infection took a turn for the worse. It’s incumbent on us to do everything possible to make sure that doesn’t happen again.”
It was a pleasure to hear from Dr Weinberger, and we are so grateful that he put so much thought into his answers. To participate in his roundtable at the World Vaccine and Immunotherapy Congress this week make sure you sign up in advance – it is surely not to be missed!
The UK government announced in November 2022 that it would be introducing a “Vaccine Taskforce style approach” to some of the biggest health challenges facing the UK. Pledging over £113 million towards research, the government has identified 4 healthcare “missions”: cancer, obesity, mental health, and addiction. The hope is that this will “unlock the next generation of medicines and diagnostics to save lives, transform patient care, and ensure UK patients are the first to benefit”.
Following vaccine success
The announcement on 28th November identified the “Vaccine Taskforce model” as the driver behind one of the “most successful vaccine roll outs in the world”. Through this approach the government aims to “harness world-leading research expertise, remove unnecessary bureaucracy, strengthen partnerships, and support the new healthcare challenges”.
Furthermore, it is hoped that addressing these challenges will “save the NHS and the economy billions of pounds”. The government estimation is that obesity costs the NHS £6.1 billion a year and “poor mental health” costs the economy £118 billion a year. The decision builds on the earlier Life Sciences Vision.
Life Sciences Vision
Launched in July 2021 under the supervision of former Prime Minister, Boris Johnson, the Life Sciences Vision was “co-developed with business and experts” to promote “scientific excellence” alongside the “dynamism of industry”. It addressed 7 key “missions”:
Accelerating the pace of studies into novel dementia treatment
Sustaining the UK’s position in vaccine discovery, development, and manufacturing
Treatment and prevention of cardiovascular diseases and major risk factors, including obesity
Reducing mortality and morbidity from respiratory disease in the UK and globally
Addressing the underlying biology of ageing
Increasing the understanding of mental health conditions, including work to redefine diseases and develop tools to address them
The model allegedly attracted £1 billion investment to the UK. This further funding is expected to gain additional investment from leading global companies.
Funding to top priorities
The top health priorities were identified by the NHS and will receive the following funding allocations:
Cancer – £22.5 million towards immune-based cancer therapies, including cancer vaccines, as well as technologies that enable earlier and more effective diagnosis.
Mental health – £40.2 million towards research to develop and introduce digital technologies, including technology to allow patients to self-monitor at home and report to doctors when in need of help.
Obesity – £20 million to trial medicine delivery and technologies for patients living with obesity, particularly in deprived communities.
Addiction – £30.5 million towards the acceleration of new technologies to prevent deaths from overdoses
How will it work?
As with the Vaccines Taskforce, the 4 missions will be chaired by an independent “expert in that field”. They will be able to supervise the accelerated “development and introduction of the latest treatments and technology into the NHS” as well as greater collaboration. The chairs will be appointed by an “expert panel dedicated to each mission”. This panel will include Kate Bingham who “headed up” the Vaccine Taskforce.
The government emphasised its commitment to ensuring patients benefit from the latest treatments. It coincides with Innovate UK’s launch of a new £30 million fund to “advance life-changing cancer therapeutics”. This is “directly supports” the government’s cancer mission, by “combining expertise in immuno-oncology and the vaccine capabilities developed throughout the pandemic”.
Senior figures meet
The statement from the government indicated that on 28th November the current Prime Minister Rishi Sunak, alongside the Health and Social Care and Business Secretaries will meet with “key industry figures”. Their discussions will cover how to “deliver life-changing innovations to patients, boot NHS efficiency, and ensure the UK remains a global life sciences superpower”.
Rishi Sunak stated that the NHS faces “real pressures”. He hopes that “outcomes for patients” will improve. Furthermore, he expects to “save the NHS millions of pounds”.
“It is hugely welcome too that the highly successful Vaccine Taskforce, which procured millions of life-saving vaccines in record time during the pandemic, will now become a blueprint for how we harness the best talent and expertise from around the world and drive investment in research and development.”
Steve Barclay, Health and Social Care Secretary identified the “billions of pounds each year” that are spent of treating conditions such as cancer and obesity. By “leading the way” in research he hopes to “ensure a better quality of life for patients”.
“By harnessing the same spirit of innovation that delivered the vaccine rollout and working hand in hand with the NHS, industry, and healthcare experts we’re building a stronger, healthier NHS with record numbers of staff and record funding”.
For more on governmental roles in vaccine delivery and how the vaccine community can work with policy makers in the future, come to the World Vaccine Congress in Washington next year.
In November 2022 it was reported that a child, around the age of 6, had died after catching an infection caused by the group A streptococcus bacteria. Another child was hospitalised and is showing signs of recovery after the bacteria outbreak at a primary school in Surrey.
The CDC suggests that group A strep is the cause of several different infections, ranging from minor illnesses to serious and “deadly” diseases. It is highly contagious but treatable with antibiotics. In England and Wales, it is a notifiable disease, which means health professionals must report suspected cases to local health protection teams in order to facilitate fast treatment and effective outbreak control.
The UKHSA confirmed on 24th November that a child had died, with “precautionary” measures being taken to protect staff and pupils at the school. The school described the “shock” to the community and emphasised that the staff would be seeking health advice so that they could act on it and support parents. Ruth Hutchinson, director of public health for Surrey County Council, offered “sincere condolences” to the school community.
Experts weigh in
Dr Timothy Jinks, Head of Interventions for the Infectious Disease team at Wellcome tweeted a link to the BBC story, suggesting that it was news that “shouldn’t be happening”. Identifying the problem of AMR as having “undermined usefulness of half of the commonly prescribed drugs” against GAS, he suggested that illness “should be prevented with vaccines” and referred to the Strep A Vaccine Global Consortium (SAVAC).
SAVAC describes GAS as the “biggest infectious killer that no one has heard of”. It causes an estimated 517,000 deaths each year, largely in low- and middle-income countries. SAVAC is working towards the development of “safe, globally effective, and affordable” vaccines to protect against GAS.
We will hear more from Dr Neeraj Kapoor, the Director of the Group A Strep and Periodontitis Vaccine Programmes at Vaxcyte, on progress towards GAS vaccines next week at the World Vaccine and Immunotherapy Congress.
A study published in Science in November 2022 has given experts in the UK reason to predict that a universal flu vaccine might be available sooner than previously hoped. Scientists in the US shared evidence that their experimental mRNA vaccine offered broad protection against all 20 known influenza A and B virus subtypes in mice and ferrets.
The potential to face flu
Influenza viruses evolve constantly, and, as the authors of the study acknowledge, this can “make targeting optimal antigens difficult”. One solution to this difficulty is broadly neutralising antibodies, but “they present their own pitfalls”, such as “limited cross-reactivity” and the need for multiple injections. The paper suggests that it is particularly difficult to be successful in creating “effective prepandemic vaccines” without certainty of which virus subtype will cause the next pandemic.
Thus, researchers developed a nucleoside-mRNA-lipid nanoparticle vaccine encoding haemagglutinin antigens from “all 20 known influenza A virus subtypes and influenza B virus lineages”. In animal studies, involving mice and ferrets, the multivalent vaccine “elicited high levels” of cross-reactive and subtype-specific antibodies” that reacted to all 20 encoded antigens.
“Our studies indicate that mRNA vaccines can provide protection against antigenically variable viruses by simultaneously inducing antibodies against multiple antigens.”
The antibodies reportedly remained at a stable level for up to 4 months. According to Professor Peter Palese of the Icahn School of Medicine in New York, the mouse and ferret models “are as good as animal models get”. Therefore, the animal data is “promising” and a “good indication of what will happen in humans”.
How soon could we see this vaccine?
Professor Palese told New Scientist that the key benefit of mRNA vaccines is the potential to easily scale them up, compared with other approaches. However, for Dr Albert Osterhaus, “further exploration in clinical studies” is needed. He refers to “previous studies” that demonstrate the difficulty of predicting what clinical data might bring.
Experts in the UK have indicated that the data so far is promising. Professor John Oxford of Queen Mary University told BBC’s Radio 4 that expecting to see it next winter would be “stretching it” but that he would “put [his] cash on the winter afterwards”.
“I cannot emphasise enough what a breakthrough this paper is.”
Professor Oxford hopes that, with mRNA technology, we can tackle the “two beasts of the jungle, the respiratory jungle”: flu and Covid. Although we tend to “underestimate these big respiratory viruses”, we must “get a grip” on them, and influenza will be the next “big beast” for us to tackle.
The Telegraph suggests that we still need to understand how to “judge efficacy and potential regulatory requirements for a vaccine against possible future viruses that are not currently circulating”. This was the sentiment conveyed in a complementary commentary to the study. Although this is a promising step, further data is required before we get ahead of ourselves, particularly as we aim to “get a grip” on influenza.
We will hear more on approaches to influenza at the World Vaccine and Immunotherapy Congress next week in San Diego. To join us, get your tickets now.
The WHO announced in November 2022 that almost 40 million children were “dangerously susceptible” to the “growing threat” of measles following a decline in vaccination coverage. This decline is recorded from the beginning of the COVID-19 pandemic and is observed across a range of routine childhood vaccinations.
A worrying decline
The statement from WHO, published on 23rd November 2022, suggested that WHO and CDC data identified 25 million children who had missed their first dose and a further 14.7 million children who missed their second dose.
“This decline is a significant setback in global progress towards achieving and maintaining measles elimination and leaves millions of children susceptible to infection.”
In 2021 we experienced an estimated 9 million cases, with an unfortunate 128,000 deaths. 22 countries had “large and disruptive outbreaks”. This is attributed to “declines in vaccine coverage”, poor surveillance, and COVID-19 related disruptions.
A grave situation
Measles is “one of the most contagious human viruses but is almost entirely preventable through vaccination”. Herd immunity can be obtained with coverage of 95% and higher. Sadly, we are “well under” this, with only 81% of children receiving the first dose of a measles-containing vaccine, and only 71% of children a second.
“These are the lowest global coverage rates by the first dose of measles vaccination since 2008, although coverage varies by country”.
Dr Tedros Adhanom Ghebreyesus, Director-General of WHO, identified the “paradox of the pandemic” as the contrast between the “record time” of the “largest vaccination campaign in history” and the disruption of routine immunisations.
“Getting immunisation programmes back on track is absolutely critical. Behind every statistic in this report is a child at risk of a preventable disease.”
Calls to action
No WHO region has achieved and sustained elimination of the virus. Furthermore, 10 countries that had previously eliminated measles have experienced outbreaks since 2016. This is concerning to CDC Director Dr Rochelle P. Walensky, who suggests that “public health officials can use outbreak response to identify communities at risk”. In doing so, she hopes that they will be able to “deliver locally tailored solutions to ensure vaccinations are available to all.”
CDC and WHO now “urge coordinated and collaborative action”, as is their wont. In addition, several WHO partners have come forward to comment on the situation. Gail McGovern, President and CEO of the American Red Cross emphasised the importance of “averting needless deaths”.
“It is imperative we work together to close existing immunity gaps and ensure that no one suffers from vaccine preventable diseases.”
Gavi’s CEO, Dr Seth Berkley describes the decline in measles coverage as “alarming”. Gavi’s support for lower-income countries will continue to “get routine immunisation programmes back on track”. Furthermore, it is “pushing” with “targeted efforts” to reach zero dose children. Elizabeth Cousens, President and CEO of the United Nations Foundations agrees that “plummeting measles vaccination rates should set off every alarm”.
“There is no time to waste.”
The alarm motif continues in a comment from UNICEF’s Chief of Immunisation Ephrem Tekle Lemango. His team have been “sounding the alarm” for 3 years and he demands “decisive action”. So, how can a world battling vaccine reluctance and emerging from COVID-19 spring back into defensive mode against a vaccine preventable virus? Will “coordinated and collaborative action” engage communities in hard-to-reach areas, and will vaccines reach every child?
For more on measles vaccination programmes at the World Vaccine Congress in Washington next year, get tickets at this link.
A research paper published in Science Advances suggests the possibility of UTI prevention through a sublingual vaccine. The paper, released in November 2022, details the success of the vaccine in mice and rabbits, indicating that there is hope for human solutions. Researchers from Duke University in the USA believe that their vaccine, which targets the uropathogenic Escherichia coli (UPEC), the cause of 80% of uncomplicated UTIs, can be a gentler alternative to antibiotics.
The authors suggest that the “major health problem” of UTIs affects “millions” every year. Specifically, 50% of all women are believed to suffer from a UTI in their lifetime. The current option for managing this is “long-term antibiotic use”.
There are risks associated with antibiotic taking, particularly for gut microbiota. The study describes how, in addition to drug-specific adverse effects, prolonged antibiotic use alters the microbes’ “metabolic activity, gene expression, and protein synthesis”, as well as reducing “diversity” as a whole. However, risks are not limited to the direct effects of the drugs, but the growing resistance to them. Modelling suggests that by 2050, “current practices would result in 10 million additional deaths per year by infection”.
“Antibiotic resistance compounds the effects already associated with prolonged antibiotic resistance use, making it likely that safe, effective treatment and prevention of UTIs will become increasingly challenging.”
UPEC have become “increasingly resistant” to common antibiotics. Therefore, the study infers an “urgent unmet need” for a “more effective form of UTI prevention”.
With this “unmet need” in mind, the authors considered the possibility of a vaccine that “raises protective, long-term antibody responses against UTI-causing bacteria”. With no such vaccine available, and “significant” barriers to its development, their task seemed a “major challenge”.
“An ideal vaccine candidate would elicit immune responses that are specific to UTI-causing bacteria to avoid adverse effects to the microbiota while also targeting a broad range of UTI-causing pathogens.”
The assumption that protection against UTIs relies on “systemic responses in the blood and mucosal responses in the urogenital tract” suggest that the vaccine should:
Be able to raise simultaneous responses against multiple highly specific and carefully selected epitopes targeting only pathogenic bacteria
Be able to elicit mucosal responses
Feature efficient dosing regiments that facilitate compliance and minimise cost
With a supramolecular approach the researchers assembled multiple selected B cell epitopes from UPEC into “sublingually immunogenic nanomaterials”. This method of administration is “known to elicit antibody responses in the urogenital tract”, but it is hard to “raise robust immune responses against short peptide epitopes” this way, as peptides are “poorly immunogenic via the oral mucosa”. However, they were able to demonstrate with model epitopes that supramolecular peptide nanofibers “bearing polymer modifications modulating mucus adhesivity” can raise “strong systemic and mucosal antibody responses”.
In the study the authors mine the “unique advantages” of their platform. In mice the vaccine elicited “robust anti-UPEC antibodies that were not cross-reactive against commensal E. coli. Furthermore, it was “as effective as high-dose oral antibiotics” at protecting mice from “lethal challenge with UPEC”.
“We report a novel vaccination strategy, enabled by biomaterial design, that provides long-lasting, antibiotic-level efficacy against UPEC.”
As the tablet can be self-administered and is stable at room temperature, it is easy to store, deliver, and administer. This has the potential to “lower costs of vaccine delivery”, suggests Sean Kelly, an author of the paper. Co-author Professor Joel Collier intends to “conduct biodistribution and safety studies” before clinical trials. His team are “actively seeking partners to accomplish this”.
Dementia is described by the NHS as a syndrome associated with an “ongoing decline of brain functioning”. This may manifest in an impaired ability to remember, think, or make decisions, suggests the CDC. The most common type of dementia is Alzheimer’s disease, and although dementia generally affects older patients, it is not considered a “part of normal ageing”. The WHO states that around 55 million people worldwide who experience dementia, with 10 million cases added each year. For these patients and their families, the experience of dementia can be deeply upsetting, confusing, and frightening. So, how do we deal with it now?
Current efforts and immune potential
FDA-approved drugs comprise 2 categories of Alzheimer’s treatment. The first option is to change disease progression, and the second is to temporarily mitigate some symptoms. However, we do not have a cure for Alzheimer’s disease or most cases of dementia.
Therefore, researchers are exploring the possibility of protection from dementia through vaccination. We are familiar with the traditional approach of vaccines, which encourage or train the immune system to respond to specific infections. Might this be applicable to dementia? Dr David A. Merrill, of Providence St John’s Health Centre in Santa Monica, told MedicalNewsToday that a growing “appreciation” of the immune system’s role indicates it might be “relevant” to “potentially recovering from or even preventing a disease”.
For example, research presented at the Alzheimer’s Association International Conference in 2020 suggested that flu and pneumonia vaccinations were associated with a reduced risk of developing Alzheimer’s. Dr Merrill suggests that “treatments can and should involve helping or addressing immune system function with ageing”.
How would a vaccine work?
Dr Heather Snyder of the Alzheimer’s Association described an exciting time for research, with numerous therapies in development. However, she is also interested in “active immunisation, such as vaccines”.
“They are, in some cases, leveraging the biology of decades of vaccine-related development more broadly in medical care.”
Some of the molecules in the body that are associated with dementia would be targeted by a dementia vaccine. These include:
Beta-amyloid proteins – abnormal levels of these form plaques that disrupt cell function
Tau – proteins that stabilise the structure of neurons in the brain, often abnormally folded in Alzheimer’s patients’ brains
Alpha-synuclein – a protein in neurons that is associated with Parkinson’s disease and Lewy body dementia in abnormal levels
Who is exploring vaccines?
MedicalNewsToday suggests that several vaccines are in various stages of clinical trials. These include a nasal vaccine in the US, and a Swiss-based candidate. Vaxxinity also announced in 2022 that it had received fast-track designation for an immunotherapeutic vaccine for Alzheimer’s disease.
Dr Michael G Agadjanyan at The Insititute for Molecular Medicine in the US is developing a vaccine for Alzheimer’s that can “delay/halt the onset”. The goal, he suggests, is to develop an “immunogenic vaccine that can induce a sufficient level of antibodies in the periphery of all vaccinated cognitively unimpaired elderly with immunosenescence”.
Although several options are being explored, Dr Merrill believes it will take a “number of years” for candidates to get through the process and “regulatory hurdles”. Furthermore, Dr Snyder thinks that “more research in large, diverse human populations” is needed before any chance of “comment on the potential usefulness of a vaccine”.
Is this likely?
There is also the concern that people might be hesitant towards vaccines for dementia, particularly depending on the length of the vaccination process. If there is a clear indication that it “truly protects” the patient, Dr Merrill hopes people would “line up”. However, things at the moment are “uncertain”.
As well as public reluctance, there is debate among the scientific community as to whether a vaccine would be successful. Dr Karl Herrup of the University of Pittsburgh School of Medicine believes that attempting to harness the immune system against the predicted root causes of the disease, “rests on shaky grounds”. Specifically discussing therapies, he describes the “bitter disappointment” of results that are “not surprising”.
“I would rather be wrong and have a useful Alzheimer’s disease therapy than be right and have to have millions of people continue to suffer”.
He suggests that the only significant question is if the treatment can “meaningfully alter the disease course”.
To hear more about vaccine therapies and protection at the World Vaccine and Immunotherapy Congress get your tickets now. Or, join us next year in Washington for the World Vaccine Congress 2023.
As we gear up towards the World Vaccine and Immunotherapy Congress in San Diego later this month we have been meeting a few of our speakers to get some exclusive insights before their sessions. Dr Stephen Johnston will be representing Calviri Inc. as founding CEO. With almost 200 peer-reviewed papers and 45 patents, as well as teaching positions, his time is precious, so we were very lucky to secure a moment for a zoom interview.
Introducing Dr Johnston
Dr Johnston kindly gave us an overview of Calviri’s work, developing vaccines and diagnostics for cancer.
What can we expect at the Congress?
Although we want to save the best for the Congress, we asked Dr Johnston for a quick preview of some of the content. He explained that he will be trying to encourage his colleagues to accept a “different perspective” on cancer vaccines. He believes they can be “simpler”, less “complicated”, and “less expensive”.
What changes does Calviri Inc. hope to bring to the field?
Anyone who might be familiar with Calviri’s website will know that “outdated” isn’t the strongest term used to describe current approaches to cancer. Dr Johnston acknowledges that this might be a bit “incendiary” but suggests that it’s how he sees it. With “50 years” and “2 Moon Shots“, there “isn’t much to show” for the hard work that has been done. Furthermore, the progress that has been made is inaccessible to people who need it most.
“People sometimes forget that of the 10 million cancer deaths a year, about 7 million of those occur in the developing countries”.
For Dr Johnston and his team, the first key strategy is “early detection”, which leads to higher cure and longer survival rates. Next, they hope to pair this with a “simple, safe, systemic” treatment – a vaccine in their case. Targeting the major cancers, they are creating off-the-shelf solutions.
In a lot of our previous posts we have explored some of the challenges associated with cancer vaccine development. For Dr Johnston, the main issue is targeting key “components” in the make-up of the cancer. He suggests that until now the “community thought that that wasn’t possible” because they were looking at DNA, instead of RNA. Thus, Calviri’s new approach takes on the RNA components that are shared across patients and even tumour types.
How do you keep people motivated?
Our next question reflects the longevity of cancer and the difficulty we have had in developing therapies and preventative measures so far. Dr Johnston suggests that instead of accepting the idea that it is impossible, his team are investigating whether their technology can be applied to cancer prevention.
“Could you design a vaccine to give to people, so that they don’t get it in the first place?”
They have shown in a study in 800 dogs that it is possible to prevent cancer, and so they hope to take this to the next stage in human prevention. The trial in dogs was the “largest” trial in dogs that has ever run, and Dr Johnston believes that after this challenge, humans are “probably easier”.
Accessibility in mind
Dr Johnston mentioned earlier in the interview that accessibility has a huge influence on his work. When we asked more about this, he stated that the team had set goals to meet in terms of production costs, in order to keep the vaccine affordable. They are “quite confident” that this can be done; Dr Johnston emphasises this by suggesting that if dogs can be easily vaccinated then the vaccine can be administered in developing areas. Not only that, but he expects it do be done “profitably”.
Looking forward to the Congress
Our final question gets to the bottom of Dr Johnston’s attendance at the Congress later this month, apart from the importance of sharing his work with others! He explained that he is “open” to hearing from people with platforms that he and his team could use. Having spoken to a few colleagues already, he is looking forward to meeting in person to further the conversation. Finally, he is testing the waters of the cancer community. Previously it has been “rutted” and “stovepiped” so this will be an opportunity to see how imaginative people are prepared to be in the future!
We are grateful for Dr Johnston’s time, particularly so close to the Thanksgiving holiday. If you are curious about his work and want to learn more at the Congress, get your tickets now.
In November 2022 the results of the AELIX-002 trial were published in Nature by collaborators from Aelix Therapeutics and Gilead Sciences. This is the trial that Dr Christian Brander, Co-founder and Chief Scientific Officer at Aelix Therapeutics, hinted at in our exclusive interview during the World Vaccine Congress in Barcelona 2022. Dr Brander is reportedly “excited” to have his team’s results recorded in a “prestigious journal” with a global reach.
The trial in context
The WHO reported that in 2021 38.4 million people were living with HIV. WHO’s strategy for 2022-2030 aims to “reduce HIV infections from 1.5 million in 2020 to 335,000 by 2030”. UNAIDS reports that 28.7 million people were accessing antiretroviral therapy in 2021.
The authors of the study note that therapeutic vaccines targeted to HIV-specific immunity have been “postulated to be a key component of any HIV cure strategy”. Despite the safety and immunogenicity of different candidates in trials, “no reduction in HIV-1 viral reservoirs, prevention of viral rebound, or suppressed viremia off ART have been reported” in trials such as this one.
A “potential reason” for previous “suboptimal trials outcomes” might be “T-cell immunogen designs and the induction of virus-specific T-cell responses with ineffective or insufficient antiviral activity”. In order to overcome this issue, HTI (HIVACAT T-cell immunogen)-based vaccines were designed to “induce functional HIV-1-specific T-cell responses that were associated with better viral control”.
The trial meets endpoints
The trial was a “double-blind, randomised, placebo-controlled trial” with the primary objective of safety evaluation. The secondary objectives “included T-cell immunogenicity, the effect on viral rebound, and the safety of an antiretroviral treatment interruption” (ATI). The study “demonstrated that HTI vaccines were safe, well-tolerated, and able to induce strong, polyfunctional, and broad CD4 and CD8 T-cell responses focused on the HTI immunogen sequence”.
“The AELIX-002 trial results support the idea that the induction of HIV-specific T-cells is a key factor in improving post-rebound viral suppression during an ATI, while validating the design of the HTI immunogen to induce functional T-cell responses to vulnerable sites of the virus”.
The authors believe that their findings “strongly support” the further use of HTI vaccines in “simpler regimens, given alone, or in combination”. A second study is also being conducted in collaboration with Gilead, according to Pipelinereview.com. Dr Brander remarked that the “T-cell vaccine approach has the potential to play a critical role in strategies to cure HIV infection”.
“AELIX is a leader in developing vaccine-based solutions for an HIV cure.”
For more on HIV strategies at the World Vaccine and Immunotherapy Congress get your tickets now.
In November 2022 the WHO launched a strategy to “respond to the urgent problem of antimalarial drug resistance in Africa”. This coincided with World Antimicrobial Awareness Week, which aims to “improve awareness of the growing threat of resistance to antibiotics and other medicines”. This strategy is focused on malaria to address reports of “emerging parasite resistance to artemisinin”.
Artemisinin is the core compound of “the best available medicines to treat malaria”. It is derived from the sweet wormwood plant, Artemisia annua, and its antipyretic properties have long been recognised. The active agent was isolated in the 1970 and has since been used to rapidly treat malaria. Alongside artemisinin there are “worrying signs” that some parasites may be resistant to drugs that are frequently combined with the treatment.
“Vigorous measures are needed to protect their efficacy.”
Although these are concerning updates from WHO, Dr Pascal Ringwald, lead author of the strategy and a Coordinator in the WHO Global Malaria programme advised health care providers to “continue to prescribe and use ACTs to treat confirmed malaria”. ACTs are artemisinin-based combination therapies, which Dr Ringwald suggests remain the “best available treatment” for “uncomplicated P. falciparum malaria.
The WHO statement suggests that this parasitic resistance to artemisinin has been observed in the Greater Mekong subregion and “several areas in Africa”. Although the “treatment remains highly efficacious” there are fears of “lacking” data and “contradictory findings”. The statement also indicates that Africa’s “heavy reliance” on ACTs could have “serious consequences” if we experience a “full-blown treatment failure”. Dr Dorothy Achu, WHO’s Team Leader for Tropical and Vector Borne Diseases for the WHO African Region, states that “we don’t have that many options for malaria drugs”.
“Any threat to these drugs could lead to lots of cases and deaths, which we obviously want to avoid.”
To assess the extent to which this would affect cases, researchers at Imperial College London produced a model in 2016. They estimated that we would see 16 million more malaria cases each year, resulting in up to 80,000 additional annual deaths. The economic consequences could hit an estimated U$ 1 billion.
The WHO strategy reportedly “builds on lessons” from previous plans and “complements existing strategies”. Among these are “broader efforts” against AMR. 4 pillars will be initiated, with 20 interventions in total. These are displayed in WHO’s infographic below.
“All of these interventions require strong health systems and investments in primary health care, which are the backbone of any successful response to malaria.”
As we explored with Dr Charlie Weller in an interview several months ago, vaccines present a “huge” but “under-recognised” potential for our AMR toolbox. She also highlighted the importance of a “coordinated and multifaceted approach” against pathogens that are currently drug resistant, but also those that are “on a trajectory” to become so.
For more on malaria vaccines and therapies at the World Vaccine and Immunotherapy Congress this month, get your tickets now. At the World Vaccine Congress in Washington next April, we will have sessions dedicated to addressing the burden of AMR. We hope you can join us!