Positive partnerships for malaria prevention

Positive partnerships for malaria prevention

Malaria threatens almost half of the world’s population, with the WHO estimating a 2020 death toll of 627,000. However, it is a preventable and treatable disease. In August 2022 the Financial Times suggested that “partnerships with governments and NGOs can help advance efforts for future generations”. The article stated that a child dies from malaria each minute, with children under 5 being the most vulnerable population group.  

In June 2022 the Rwandan government hosted the Kigali Summit on Malaria and Neglected Tropical Diseases (NTDs). Discussions addressed the “urgency of ending malaria and NTDs”. Ahead of this Summit, SC Johnson announced a partnership with The Global Fund to “accelerate the elimination of malaria”. The Chairman and CEO of SC Johnson, Fisk Johnson, stated that his company has been “working for decades on preventative interventions and innovative solutions” but “can’t tackle this insidious disease alone”. SC Johnson has been developing Mosquito Shield for almost a decade. The “low-cost, effective indoor spatial repellent” is ideal for use where “core interventions may be constrained”.  This development, with public health partners, is another sign of SC Johnson’s commitment to the cause. 

Peter Sands, Executive Director of The Global Fund, believes that SC Johnson’s “strong expertise in entomology” will be a “key asset” against malaria. He is glad to see the private sector contributing “innovative solutions and technical expertise” to the fight. The Financial Times described the partnership as an “example of how private and public sectors can work together” through “entomological surveillance, end-user behavioural research, and product acceptability and use research”.  

Throughout the last decade SC Johnson has committed more than $100 million to public health efforts in Africa. With this most recent partnership it will dedicate another $10 million. In 2021 the company joined the Society for Family Health Rwanda and East African Community leaders by signing a Memorandum of Understanding to tackle malaria. The goal is the reduction of mortality by 50% in 2025, ultimately eradicating it completely. 

This partnership comes just ahead of The Global Fund’s Seventh Replenishment Conference 2022. Hosted by the US President, the target is “to raise at least US$18 billion to fund its next three-year cycle of grants”. This would contribute to life-saving treatments and preventions for 20 million people. Looking ahead to a “brighter future”, this partnership may be a step in the right direction to eliminate one of the world’s most prolific diseases.

To hear about progress towards malaria vaccines at the World Vaccine Congress in Europe 2022 click here to buy tickets.
 

AI turns its sights to drug discovery challenges

AI turns its sights to drug discovery challenges

The WHO states that cancer is a “leading cause of death worldwide”. It accounted for nearly 1 in 6 deaths in 2020; that’s almost 10 million. Each year millions of pounds are pumped into cancer research across the world, yet deaths are likely to increase over the next 20 years because of ageing populations.  

Although increasing numbers is an unhappy prospect, we can take comfort in the increased financial and intellectual investment into technology against cancer. One area hoping to tackle understanding and drug development is artificial intelligence, said Pharmaphorum contributor Ben Hargreaves. He predicts that the potential AI offers will lead to an increase in companies emerging in the space, with “a greater number of collaborations occurring between these AI-specialists and big pharma”.  

Hargreaves identifies Owkin, a medical AI company founded in 2016, which is focusing on cancer. A recent partnership with the Francis Crick Institute and The Royal Marsden NHS Foundation Trust will enable Owkin to research kidney cancer.  

“The aim is to help doctors provide more effective treatments to patients, as cases of kidney cancer continue to increase”. 

We can expect to see exciting developments from this partnership, as failing treatments can be influenced by “intratumour heterogeneity”. Using histology slides to predict tumour evolution, Owkin hopes to predict outcomes in each patient so that treatment can be tailored.  

However, Owkin’s tools are not limited to treating cancer. Hargreaves reports that it can “interpret histogenomic biomarkers to discover and rank genes and proteins with drug target potential”. This would be exciting news for the industry, which currently faces a drug development failure rate of 96%.  

Owkin has partnered with bigger companies such as Sanofi and Bristol Myers Squibb. Another company that has recently forged a deal with Sanofi is Exscientia. CEO Dr Andrew Hopkins suggests that using AI in drug design has dramatically reduced the pipeline duration. Comparing traditional approaches, taking between 4 and 5 years, to AI approaches, which take “only 12 to 15 months”, there is a clear winner.  

As Hargreaves suggests, the potential within the AI field will attract the attention of investors, hopefully accelerating advances in drug development. For cancer treatment and wider drug research, putting AI to work promises to pay off.  

To hear from Sanofi speakers at the World Vaccine Congress in Europe in October, click here for tickets.  

Climate health is global health, study concludes 

Climate health is global health, study concludes 

In August 2022 a study in Nature concluded that 58% of infectious diseases we face are “aggravated by climatic hazards”. The authors identify “global distress” caused by “human vulnerability to pathogenic diseases”. 

This literature study describes how “empirical cases revealed 1,006 unique pathways in which climate hazards, via different transmission types, led to pathogenic diseases”. Among the research were different links between climate hazards and disease, some of which are highlighted below. 

Climate hazards bringing pathogens closer to people: 

The study reflects that “shifts in the geographical range of species are one of the most common ecological indications of climate change”. For example, “warming and precipitation changes” can be linked to the “range expansion” of a variety of vectors. These include “mosquitoes, ticks, fleas, birds and several mammals” as well as “bacteria, animals and protozoans”. Expansions were also perceived in aquatic systems.  

Disruptions to natural habitats caused by factors such as drought, wildfires, floods, and land cover change are also “bringing pathogens closer to people”. Viral spillovers were linked to wildlife moving over “larger areas” in search of resources or habitats. In a dystopian conclusion, warming was related to “melting ice and thawing permafrost exposing once-frozen pathogens”.  

Climate hazards bringing people closer to pathogens: 

Climate hazards push the global population closer to pathogens in a variety of ways. For example, heatwaves increase instances of “recreational water-related activities”, associated with “rising cases of several waterborne diseases”. Human displacement, caused by floods and storms, has seen an increase in cases of Lassa fever, typhoid, and pneumonia, among others. Furthermore, land use changes provoke “human encroachment into wild areas”. This brings people “into closer proximity to vectors and pathogens”. 

Pathogens strengthened by climatic hazards: 

Climatic hazards also provide enhancement to certain aspects of pathogens. These include “improved climate suitability for reproduction, acceleration of the life cycle, increasing seasons/length of likely exposure, enhancing pathogen vector interactions, and increased virulence”. For mosquitoes, increased temperatures saw positive effects on population development and viral replication. Consequently, the “transmission efficiency” of West Nile virus was increased.  

Virulence is also linked to climatic hazards in the study. The researchers consider heat, which was “related to upregulated gene expression of proteins affecting transmission, adhesion, penetration, survival, and host injury by Vibrio spp”. Furthermore, heatwaves are considered a “natural selective pressure” towards viruses that are heat resistant. These viruses are thought to then be better able to respond to fever in the human body.  

People impaired by climatic hazards: 

Our ability to respond to pathogens has been affected by climatic hazards as well. The study identifies “stress from exposure to hazardous conditions”, weakened infrastructure, unsafe conditions, and reduced access to treatment. Citing “body malnutrition and condition” as an example, it reflects that “immunocompetence” is greatly impaired by increased exposure to hazards.  

Although the examples above paint a very alarming picture, the study includes some diseases that were “diminished” by climatic hazards: 16%. For example, warming “appears to have reduced the spread of viral diseases probably related to unsuitable conditions for the virus or because of stronger immune system in warmer conditions”. However, many diseases that were “diminished by at least one hazard” were sometimes “aggravated by another and sometimes even the same hazard”. The is exemplified in malaria, which was reduced through drought decreasing breeding grounds. At the same time, drought can lead to “increased mosquito density” in bodies of water.  

The conclusion is overwhelmingly negative, and the authors conclude that collaborative and proactive efforts must be increased. As attempts to tackle climate change continue, some are preparing for the many pathogens that follow.

“The sheer number of pathogenic diseases and transmission pathways aggravated by climatic hazards reveals the magnitude of the human health threat posed by climate change and the urgent need for aggressive actions to mitigate GHG emissions.”

To hear from industry and thought leaders on how we can prepare for increasing pathogen exposure come to the World Vaccine Congress in Europe in October 2022.

Lyme disease vaccine candidate proceeds to Phase III study

Lyme disease vaccine candidate proceeds to Phase III study

Lyme disease is a systemic infection transmitted to humans by infected ticks, caused by the Borrelia burgdorferi bacteria. It is the most common vector-borne illness in the Northern Hemisphere. According to the CDC, state health departments report 30,000 cases each year. However, recent estimates suggest that it infects closer to 476,000 people annually in the US.  

Lyme disease often goes untreated due to misinterpretation of early symptoms. It then causes serious complications to the joints, the heart, or the nervous system. 

“The medical need for vaccination against Lyme disease is steadily increasing as the geographic footprint of the disease widens.” 

Pfizer’s response was to initiate a collaborative approach with Valneva. VLA15 is currently the only Lyme disease candidate in clinical development. It is an “investigational multivalent protein subunit vaccine”. Targeting the outer surface protein of the disease-causing bacteria, the vaccine is expected to inhibit the bacterium’s ability to “leave the tick and infect humans”. The vaccine addresses the most common OspA serotypes prevalent in North America and Europe.  

In studies to date, VLA5 “demonstrated a strong immune response and satisfactory safety profile”. This next phase of development requires up to 6,000 participants above the age of 5. The trial takes place across 50 sites in areas where the disease is “highly endemic”

“Pending successful completion of the Phase III study, Pfizer could potentially submit a Biologics License Applications (BLA) to the FDA and Marketing Authorisation Application (MAA) to the EMA in 2025.” 

Valneva and Pfizer started this collaboration in April 2020. The agreement states that Pfizer makes a $25 million “milestone payment” to Valneva at the start of the Phase III study. 

Dr Juan Carlos Jaramillo, CMO of Valneva, suggested that Lyme disease comprises a “high unmet medical need”. Dr Annaliesa Anderson of Pfizer agrees that “providing a new option for people to help protect themselves” is “more important than ever”. She hopes that progressing the vaccine to Phase III will provide “positive evidence” in support of the candidate.

To hear from Dr Anderson and representatives from Valneva at the World Vaccine Congress in Europe 2022 click here to get tickets.  

Immune system map uncovers therapeutic potential

Immune system map uncovers therapeutic potential

In August 2022 scientists published a “comprehensive map” of the immune system. Released in Nature in August 2022, this research is expected to open new opportunities for immunotherapies by exploring key cellular communications.  

The research identifies several “previously unknown interactions” that bring us closer to understanding immune responses. All knowledge of the interactions between immune cells is “vital” in developing immunotherapies. Furthermore, understanding the “cell-to-cell” signals within the immune system allows researchers to pursue preventative measures against autoimmune diseases.  

“The map of immune receptor connections could help explain why immunotherapies sometimes only work in a subset of patients, and offer new targets for designing future immunotherapies” 

The researchers “isolated and investigated” a set of the surface proteins that “physically link immune cells together”. Using computational and mathematical analysis they then detailed “cell types, messengers, and relative speed of each conversation”.  

With the map, it is possible to see the effect that each different disease has on the immune system. Then we can explore new therapies that target different proteins on the immune cell surface.  

Jarrod Shilts, first author, stated that this map is a “huge step in understanding the inner workings of the immune system”. He hopes it will be used globally to “develop new therapies that work with the body’s defence mechanisms”.  The analysis and methods used provide a “template” for investigation into “physical cell wiring networks”. The authors hope that further research will “disentangle cellular circuits in immunity and beyond”.  

To hear from researchers and industry leaders at the World Vaccine Congress in Europe 2022 click here to buy tickets.

Improving protein factories for gene therapies

Improving protein factories for gene therapies

Gene therapy tackles the source of disease in the patient’s DNA through viral or bacterial vectors. Most commonly, muscle cells are targeted because muscle injection is an accessible entrance to the body. However, muscle cells may not be capable of producing the right protein. A recently published study explores how changing protein regulation networks can enhance muscle cells’ ability to respond to gene therapy.  

AAT deficiency is a condition in which liver cells produce insufficient quantities of the protein AAT. Consequently, serious respiratory problems can develop, such as COPD or emphysema. Common treatment involves regular hospital trips for infusion or investment into expensive home equipment. However, Dr Terence Flotte developed an injectable AAT gene therapy that allows sustained AAT release over several years. Unfortunately, he found that because muscle cells can’t produce the AAT proteins, the increase after gene therapy was limited.  

The recent study explored the options for transforming muscle cells into better protein production sites, like liver cells. They tested several on mice muscle cells to see if they would boost AAT secretion and found that adding suberoylanilide hydroxamic acid (SAHA) enables this. In the future, the hope is that using SAHA or similar proteostasis regulators to gene therapies would ameliorate treatments for genetic diseases.  

This study has “implications beyond just gene therapies”, according to Professors Daniel Hebert and Lila Gierasch. They believe that mRNA vaccines, which work according to cell production of proteins, “face the same limitations as gene therapies”.  

“Increasing the protein production of muscle cells could potentially improve vaccine immunity.” 

Furthermore, lots of drugs are derived from natural sources and “rely heavily on a given cell’s protein production capabilities”. Professors Hebert and Gierasch think that a protein homeostasis enhancer could “optimise protein yield and increase the effectiveness of the drug”. This would have implications beyond drug development, for neurodegenerative diseases, for example. They look forward to further research on “ways to improve the cellular machinery” to “open many new doors” against a range of diseases.

To hear from industry leaders at the World Vaccine Congress in Europe, 2022, head to this page to buy tickets.

UKHSA under vaccine pressure as monkeypox continues

UKHSA under vaccine pressure as monkeypox continues

British LGBTQ+ groups across a spectrum of political parties wrote to the UK’s Health and Social Care Secretary Steve Barclay in August 2022 to demand urgent action against monkeypox. The letter stated that the UKHSA “has procured just over half” the required quantity of doses for 125,000 people.  

Unless action is taken, the authors are concerned that monkeypox will become “endemic in the UK”, presenting a serious health risk. It would also “exacerbate the health inequalities already experience by gay and bisexual men and other men who have sex with men” they stated.  

The letter was co-ordinated by the Terrence Higgins Trust, a UK-based sexual health charity. Ceri Smith, head of policy at the trust, identified the detrimental effects of the outbreak on other sexual health services, including STI testing and treatment, as well as contraceptive services. It is estimated that “up to 30% of sexual health appointments have been displaced” due to the pressure applied to the health service by monkeypox.  

The UKHSA suggested in early August that there were “early signs that the outbreak is plateauing”. However, the UK has one of the highest number of cases across the world, and vaccine delivery is being hindered. The doses of the vaccine that have already been procured are currently being delivered “in batches” to individuals at “higher risk”.  

The Department of Health and Social Care insisted that thousands of vaccines have already been administered and that the NHS is “working to rapidly invite those at greatest risk”. Partners such as the NHS and UKHSA are working together to “share targeted, non-stigmatising communications with the LGBTQ+ community”. This comes amidst viral debates on whether the virus should be classified an STI, and how messaging should be delivered to the public to protect vulnerable communities without further placing them at risk of discrimination or stigmatisation.  

Further to efforts to support sexual health services, the Department of Health and Social Care has stated that it will provide “more than £3.4 billion through the Public Health Grant”. This will enable local authorities to invest in “essential frontline sexual health services”.  

To participate in the monkeypox workshop at the World Vaccine Congress in Barcelona in 2022 follow this link to secure tickets.

Antimicrobial resistant bacteria discovered in new-borns

Antimicrobial resistant bacteria discovered in new-borns

A study in Nature Microbiology explored links between the presence of antimicrobial resistant bacteria isolated from mothers and their new-borns across 7 countries. The study was coordinated by Professor Tim Walsh at the Ineos Oxford Institute for Antimicrobial Research and the Oxford Department of Biology. It revealed that antimicrobial resistant bacteria are present in neonates after “just a few hours of life”. Furthermore, it found examples of transmission of “sepsis-causing resistant bacteria within hospitals from mothers to babies”. 

Almost 7 million potentially serious bacterial infections occur in new-borns. This results in over 550,000 neonatal deaths annually, many of which occur in LMICs. In these locations “scarce resources can limit the capacity to diagnose and treat sepsis”. This is exacerbated by the rise of AMR, estimated to cause 5 million deaths a year across the globe.  

In this study, Drs Maria Carvalho and Kirsty Sands joined an international network to explore the presence of antibiotic resistance genes (ARGs) in the gut microbiota in mothers and babies across 7 LMICs in Africa and South Asia. Under the Burden of Antibiotic Resistance in Neonate from Developing Societies study, BARNARDS, 35,040 mothers and 36,285 neonates were recruited.  

The researchers collected 18,148 rectal swabs and grew the bacteria from these samples. The intention was to “assess the presence of clinically important ARGS” in this population. The authors found many samples carried genes “linked to antibiotic resistance”, which indicates how prevalent AMR is in these settings. It is notable that the researchers found these ARGS to be present in neonates “within hours of birth”. This suggests that “initial colonisation of the new-borns with antibiotic-resistant bacteria occurred at the birth or soon after, likely through contact with the mother of from the hospital environment.” 

Furthermore, the study explored “risk factors associated with the carriage of ARGs”. This included features linked to “water, sanitation, and hygiene (WASH), and prior infections”. They found that better hand hygiene reduced the risk of carrying resistance genes, whereas the risk was increased if “mothers had reported an infection” or took antibiotics in the 3 months preceding the start of the study.  

The findings of the study demonstrate the importance of understanding ARG transmission in preventing neonatal sepsis. Additionally, they highlight the need for access to “safe water, sanitation, and good hygiene” to protect neonates in LMICs. Professor Walsh reflected that the “incidence of AMR carriage” is “extremely worrying”.

“Clearly this research poses many questions about transmission an also about the acquisition of these drug-resistant strains might impact on the growth of the baby”. 

For Dr Rabaab Zahra, who led the study in Islamabad, the study “raises concerns about our policies on antibiotics use, along with hygiene and infection control practices in healthcare facilities.” The study also had an effect in Kano, Nigeria. Dr Fatima Modibbo suggested that until the study, “blood cultures were not routinely implemented”. Since then, patterns in blood cultures have led to “lifesaving changes” and a “reduction in neonatal mortality rates”.  

For a day of AMR discussion at the World Vaccine Congress in Europe 2022 head to this page to get your tickets.

Emerging emergencies require top authority

Emerging emergencies require top authority

In July 2022 the Director-General of the WHO, Dr Tedros Adhanom Ghebreyesus, declared monkeypox to be a Public Health Emergency of International Concern (PHEIC). This is the seventh of its kind since 2005.  

The PHEIC is overseen by the International Health Regulations (IHR) and is declared when the outbreak is an “extraordinary event; when it constitutes a public health risk to other states through international spread; and when a coordinated international response is potentially required.” 

The IHR formed a technical Emergency Committee (EC), comprising experts in the appropriate field of each disease. The EC informs the WHO Director-General whether a disease should be described as a PHEIC. In the previous 6 PHEICs the Director-General has taken the advice of the EC. However, in the most recent situation, the Director-General took his own initiative against the vote of the EC.  

Writing in The Lancet in August 2022, Dr Clare Wenham and Dr Mark Eccleston-Turner reflected that the decision of the Director-General to overrule the EC demonstrates the WHO is a “politically engaged actor, capable of embracing and engaging with political considerations”. They suggest that this “dimension” shows a “commitment to protecting traditionally marginalised groups from technical decision-making bodies”.  

“The decision to declare monkeypox a PHEIC is a much-needed development for an increasingly politicised WHO” 

Drs Wenham and Eccleston-Turner further suggest that during the Covid-19 pandemic the WHO lost “influence and authority” due to the deviance of member states from WHO recommendations. Therefore, the PHEIC declaration might be considered an “attempt to reclaim some authority in global disease control”.  

However, the tension between the Director-General and the EC may present member states with the opportunity to ignore recommendations from the WHO. It is hoped that the declaration might generate “increased support, vaccine production, and more equitable access to such vaccines or medical countermeasures”. 

“The PHEIC is the switch to turn on action” 

The authors note that the field, so “dominated by evidence-based decision making” will require more than the “assumption of the normative power of the PHEIC”. As we observe consecutive emergencies, we can discern the effectiveness of their nominal updates. Will monkeypox countermeasures be generated in a more collaborative fashion because of this decision? Unfortunately, only time will tell.  

To participate in a day of monkeypox discussion at the World Vaccine Congress in Europe 2022 click here to get your tickets!

Monkeypox doses stretched to the limit by NIH scientists

Monkeypox doses stretched to the limit by NIH scientists

As cases of monkeypox increase, it is evident that vaccine demand is greater than the supply. Although the FDA had previously indicated sufficient supply for double doses, scientists at the NIH are exploring alternatives to a two-shot regime in order to increase access to JYNNEOS, the vaccine licensed for use against monkeypox in the United States.  

The intention is to explore “fractional dosing”, using a fifth of the recommended dosage per person, as well as single dosage. They will compare the results with the current programme of two doses, 28 days apart. The study should provide answers as early as November, with potential to alleviate the strain on vaccine supply if positive.  

As of August 2022, more than 80 countries have recorded over 25,000 confirmed cases of monkeypox. At least 6,600 of these are from the United States. Despite this, the FDA and CDC have “stressed that the vaccine should be used as licensed”. However, there are suggestions that generous dosage recommendations from vaccine manufacturers might lend themselves to fractional dosing.  

Fractional dosing has been used effectively in previous outbreak situations, such as the 2016 yellow fever outbreak in Angola and the Democratic Republic of the Congo. At that time, global supplies of the vaccine were stretched thin and the WHO recommended doses a fifth of their usual quantity.  

The tension between dose quantity and quality raises questions about our preparedness for outbreaks of disease. Dr John Beigel of NIAID stated that there isn’t a “consistent message” but that some were getting “one dose now for six months or maybe longer”.

As the outbreak spirals, doses of the vaccine have yet to reach the “source”. Will we see another pandemic of vaccine selfishness, or will we work collaboratively to spread the vaccine as evenly as possible? 

To participate in a day of monkeypox discussion at the World Vaccine Congress in Europe 2022 head here to get your tickets!

Vertex’s “Fantasy project” with Moderna pushes CF limits

Vertex’s “Fantasy project” with Moderna pushes CF limits

Vertex Pharmaceuticals and Moderna announced in 2022 their strategic research collaboration aimed at the “discovery and development of lipid nanoparticles (LNPs) and mRNAs”. This partnership is part of Vertex’s larger project to find suitable Cystic Fibrosis (CF) treatments for all patients.  

Over 2 decades of research have gone into Vertex’s “Fantasy project”, which aims to treat the underlying causes of CF. The condition is described by Dr Fred van Goor, Vice-President of CF research, as “so complex” that treatment seems “impossible”. Not daunted by this task, he and his colleagues successfully developed medicines with the potential to treat 90% of people with CF. These medicines act by fixing a broken version of the CFTR protein.  

However, he observed that the remaining 10% of CF patients do not make this protein. Thus, a new approach is required. Through partnership with Moderna, Vertex hopes to access mRNA’s “transformational benefits”.  

Inspired by the “strength, endurance, and spirit” of the CF community Vertex and Moderna continue to pursue the research that has been ongoing for years.  

To hear from several Moderna speakers and panellists at the World Vaccine Congress in Europe 2022 click here!

Experimental RSV vaccine promise shown in mice

Experimental RSV vaccine promise shown in mice

The respiratory syncytial virus (RSV) infects almost all children before they turn 2 years old. The pathogen causes bronchiolitis chest infection, for which there are no approved treatments. RSV is estimated to kill over 59,000 children under 5 each year, and there are currently no vaccines against it.  

However, this might be about to change, according to research by Professor Ofer Levy and Dr Simon van Haren. Alongside colleagues they have developed an adjuvanted vaccine containing a fragment of a protein that RSV uses to enter cells: F protein.  

Professor Levy suggested that this vaccine was the “magic sauce” to provide infant immunity, certainly in the 12 mice that they tested on. These mice were given the vaccine or a saline solution before exposure to RSV. The mice that were given the vaccine displayed no virus in their lungs. Furthermore, the nasal concentration of RSV in vaccinated mice was “100 times lower than in the control mice”.  

Levy reported: 

“The adjuvant combination robustly enhanced antibody and useful T-cell responses and indicated protection against RSV infection in infant mice.” 

The study was limited by the fact that the mice were adults at the time of completion, whereas RSV causes bronchiolitis in young children. In fact, it was suggested in a 2017 study that “45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months”.  Thus, the next step will be non-human primates and then people, says Levy. Although humans and mice “have many similarities” they are “very different systems”. The ambition is to start human trials “within five years”.

To hear from Professor Levy on the role adjuvants in vaccines at the World Vaccine Congress in Europe 2022 follow this link!

“Shot to the heart” (of mutating viruses)

“Shot to the heart” (of mutating viruses)

As the Covid-19 pandemic continues with myriad variants, current vaccine technology is struggling to keep up. Often employing B-cell immune responses, vaccines are unable to “anticipate virus mutations”, rendering the patient “vulnerable to infection”. According to Alexandre Le Vert, CEO and Co-founder of Osivax, newer T-cell based approaches can combine with current technology to tackle the “internal, less variable, parts of viruses”. The result would be protection against immediate and future strains.  

Le Vert, in the European Pharmaceutical Review, explains how SARS and influenza typically target respiratory cells to cause inflammation. The haemagglutinin and spike surface antigens are susceptible to “spontaneous mutation”, thus presenting several shapes and splitting themselves into variants or strains. Most vaccines attack these surface antigens, but “lack the capacity to produce cross-reactive responses” to neutralise multiple strains.  

Suggesting that targeting the “more conserved regions of the virus”, Le Vert identifies that these are “less prone to mutations”. They can only be detected by the “T-cell component of the immune system”. He suggests that “several” biotechs have recognised this and are exploring vaccine solutions. Nanoparticles and mRNA vaccines have been developed to present several regions of the haemagglutinin and are known to “provide better cross-protection”.  

Another “disruptive approach”, which companies like Osivax and Imutex are exploring, comprises vaccines targeting the “heart” of a virus. This uses the T-cell approach. Osivax’s technology platform, oligoDOM, elicits a T-cell response that targets a virus’ internal antigens. So far it appears that the platform can trigger a universal response capable of multiple variants of a virus.  

This technique, deployed against influenza, demonstrated “cross-protection against all A and B strains tested”. Furthermore, in a Phase IIa trial, OVX836 displayed an “excellent safety profile”. The trial also proved strong “activation of the cellular component of the immune system”. Further trials are planned to establish the benefits of co-administration with a standard QIV.  

Looking forward, Le Vert predicts that “broad-spectrum vaccines” could offer “robust protection” against future viruses that mutate regularly. He reflects that Covid-19 highlighted a need for “improved approaches” but also “showcased” the progress that can be achieved through collaborative innovation.  

To hear Alexandre Le Vert discussing T-cell vaccine updates at the World Vaccine Congress in Europe, 2022, follow this link! 

2030 AIDS elimination goals for new WHO alliance

2030 AIDS elimination goals for new WHO alliance

The recent UNAIDS report revealed that only 52% of children with HIV are receiving life-saving treatment. However, 76% of adults with HIV are receiving antiretrovirals. The gap in coverage is “an outrage”, according to UNAIDS Executive Director Winnie Bynanyima. She hopes to “channel that outrage into action” over the next few years.  

In August 2022 UNAIDS, UNICEF, WHO, and partners have formed a “global alliance” to provide essential treatment to every child with HIV and prevent new infections by 2030. It will be politically launched in Africa at a Ministerial meeting in October 2022.  

The Global Alliance for Ending AIDS in Children by 2030 was launched at the International AIDS Conference in Canada. It includes UN agencies, “civil society movements”, and international partners. 12 countries have joined the initial phase: Angola, Cameroon, Côte d’Ivoire, the Democratic Republic of the Congo, Kenya, Mozambique, Nigeria, South Africa, Uganda, the United Republic of Tanzania, Zambia, and Zimbabwe. 

The alliance has identified “four pillars for collective action”:

  1. closing the treatment gap for pregnant and breastfeeding adolescent girls and women living with HIV and optimising continuity of treatment; 
  2. preventing and detecting new HIV infections among pregnant and breastfeeding adolescent girls and women; 
  3. accessible testing, optimised treatment, and comprehensive care for infants, children, and adolescents exposed to and living with HIV; and 
  4. addressing rights, gender equality, and the social and structural barriers that hinder access to services.  

Catherine Russell, the Executive Director of UNICEF, described this alliance as an “important step forward” towards an “AIDS-free future”. Dr Tedros Adhanom Ghebreyesus, Director-General of the WHO echoed this, suggesting that it will provide an “opportunity to renew our commitment to children and their families”. He intends to “unite, to speak, and to act with purpose and in solidarity”.

To learn about innovations in HIV vaccine technology from Dr Brander of AELIX Therapeutics at the World Vaccine Congress in Europe 2022 follow this link.

Gavi’s reasons to be optimistic: routine rises

Gavi’s reasons to be optimistic: routine rises

After woeful statistics of global vaccine uptake decreases, and the news from UNAIDS that the AIDS response is “under threat”, Gavi published an analysis of 2021 immunisation rates. As 2020 saw the “biggest drop in routine immunisation coverage”, we had little reason to be hopeful.  

In the years before the Covid-19 pandemic, lower-income countries demonstrated “two decades of skyrocketing vaccine coverage”. This was revealed in the increase of DTP3 doses from 59% in 2000 to 82% in 2019. Unfortunately, the pandemic “reversed these gains” with a total drop of 5% over 2 years. With this drop came a rise in the number of zero-dose children to 12.5 million. The consequences of this could be “felt for a generation”.  

However, there were some positive changes across the world. Over half of the 57 countries supported by Gavi “managed to stabilise or even increase coverage” in 2021.  

“Amidst the gloom there are signs of recovery and resilience.”  

Cheers to Chad and Pakistan 

A highlight in the report was the strong performance by Chad and Pakistan. Chad increased vaccine coverage throughout the pandemic. The percentage of children immunised with “basic vaccines” rose from 50% in 2019 to 58% in 2021. Although Pakistan experienced a setback during the 2020 lockdowns, it was able to return “both vaccine coverage and the number of zero-dose children close to pre-pandemic levels”.

Covid-19 vaccination successes 

The report also highlights the fact that vaccine programmes were pretty preoccupied during 2021 with the distribution of Covid-19 vaccines.  

“In fact, taking into account the two billion Covid-19 vaccines rolled out by the 57 Gavi-supported countries, 2021 saw more vaccines administered by lower-income countries than any other year in history.” 

Thanks to the persistence of health officials and volunteers across the globe, routine and Covid-19 vaccination programmes were delivered in 2021. Covid-19 vaccine coverage rose “in the 92 lower-income countries eligible for the COVAX AMC” to 48%. 

So perhaps, as we head into 2023 beset by stories of failure and fatigue, let’s consider the positive changes that were brought into effect, and push to build on these in the future.  

To hear from Anuradha Gupta, Deputy CEO of the Gavi Alliance, at the World Vaccine Congress in Washington, 2023, click here

Science suggests components for pandemic disruption treaty

Science suggests components for pandemic disruption treaty

WHO member states can expect an update from an Intergovernmental Negotiating Body in August 2022 on an “initial draft” of a treaty to “break the pandemic cycle”. In July 2022, Drs Alexandra Phelan and Colin Carlson published a recommended 12 elements for this treaty.

According to Drs Phelan and Carlson, we are “trapped in a positive-feedback loop” of disease spillovers that become outbreaks, then pandemics. These then reduce resilience and promote the “socioecological drivers” of further spillovers. The consequences are social, political, environmental, and economic. Therefore, the development of a treaty will be difficult, as “stakeholders lobby for [it] to be all things for all interests”.  

The primary purpose of this treaty is: “preventing, preparing for, and responding to pandemics”. Drs Phelan and Carlson identify 12 elements that they believe would comprise a “cohesive, transformative, and evidence-based treaty”.  

Reduce Spillover Risk 

  • Planetary health solutions 
  • One health solutions 
  • Zoonotic risk assessment 

Reduce Pandemic Risk 

  • Surveillance and assessment 
  • Biomedical R&D and production 
  • Health systems strengthening 

Reduce Pandemic Impacts 

  • Equitable access to global goods 
  • Emergency legal preparedness 
  • Least restrictive measures 

Recovery and Resilience 

  • Adaptive governance 
  • Accountability and transparency 
  • Reduce inequalities and injustice 

If a treaty can balance these aims, it will “move global health governance beyond the limited scope of the International Health Regulations” offering “clarity and complementarity to other relevant international legal regimes”.

To discuss pandemic preparation after lessons from Covid-19 at the World Vaccine Congress in Washington in 2023, click here to get your tickets!

Continuing the Covid-19 fight with monoclonal antibodies

Continuing the Covid-19 fight with monoclonal antibodies

As the Covid-19 pandemic continues across the globe, novel variants mutate and rise against current treatments. The protection afforded by vaccination wanes after a few months, and therapies that previously worked are ineffective against more recent instalments. Thus, the search for monoclonal antibodies (mAbs) against all strains continues.  

In July 2022 researchers from the National Institute of Health and Scripps Research Institute published a study in Science. They assessed the “neutralising potency” of six mAbs by introducing them to a neutralisation assay. The study concluded that COV44-62 and COV44-79 demonstrated the “broadest functional reactivity”, neutralising both betacoronaviruses and the alphacoronavirus HCoV-NL63 and HCoV-229E.  

The study notes that COV44-62 achieved neutralisation with lower concentrations, which indicates a “more effective antibody”, but that COV44-79 neutralised Omicron BA.4/5 more efficiently. Omicron continues to drive infections worldwide, so this was a significant find. Dr William Haseltine in Forbes stated that while “most monoclonal antibodies target amino acids on either the receptor-binding domain, the N-terminal domain, or a combination of the two”, the two antibodies investigated “prefer to bind in the S2 portion of the Spike, specifically the fusion peptide”.  

Dr Haseltine suggests that there is “no reason” to limit treatment to one antibody, instead favouring a “cocktail”. He predicts that this “cocktail” might be useful against current as well as future strains. Furthermore, he concludes, we must “prioritise and expedite these antibodies’ production” against the still-raging pandemic.  

To participate in discussions about the global response to Covid-19, vaccinations and therapies, get your tickets to the World Vaccine Congress in Europe 2022 here.

Hear from our WVC 2022 speaker: Dr Jennifer Nuzzo

Hear from our WVC 2022 speaker: Dr Jennifer Nuzzo

DrPh Jennifer Nuzzo, Professor at Brown University School of Public Health and speaker at the World Vaccine Congress 2022, warned that we’re not ready to prevent another pandemic. Unless public health officials take concrete steps, she fears we will experience more waves of disease.  

“This pandemic is not a one-off. It’s not a once-in-a century event. The likelihood of new pathogens emerging means we should expect a future filled with infectious disease threats that we must be ready to fight.”  

Dr Nuzzo says that governments at every level must treat this as a fundamental threat to national peace and prosperity. We should expect to encounter more respiratory viruses. Thus, we must match safety measures to these pathogens. She recommends concrete steps such as improving ventilation in buildings.  

“The progress made during Covid-19 must not be followed by quiet time in which we forget rather than work hard to prepare for the next one. We went through this hideous experience and failing to strengthen our readiness is the biggest mistake we could make.” 

Home testing was clearly beneficial in detecting and fighting Covid-19. It would be extremely valuable if we developed this for other infectious diseases, such as strep throat and influenza, Dr. Nuzzo said. This might help the public understand isolation requirements. “Simple behaviour changes” will be key to reducing the spread of other pathogens.  

“I think in some ways we will be better prepared for the next pandemic, but that is partially shaped by education and awareness. I am optimistic. There’s a tremendous number of things that we can do, and we are at that moment.”

*To hear DrPH Nuzzo at the World Vaccine Congress in Washington in 2023, click here to get your tickets!

WHO’s new infection guidelines for “key populations”

WHO’s new infection guidelines for “key populations”

In July 2022 the WHO published new guidelines on “HIV, viral hepatitis, and STI prevention, diagnosis, treatment, and care for key populations”. These guidelines were officially launched at the AIDS 2022 Conference in Canada.  

The guidelines outline a public health response to HIV, viral hepatitis, and STIs for 5 key populations: 

  • Men who have sex with men (MSM) 
  • Trans and gender diverse people 
  • Sex workers 
  • People who inject drugs 
  • People in prisons and other closed settings 

Erika Castellanos, Director of programmes at the global Action for Trans Equality (GATE) emphasised the importance of prioritising these key populations “in every setting”. She hopes to “reach them first with prevention, testing, and treatment”, prioritising them in funding programmes.  

For these populations, “social, legal, structural, and other contextual factors” increase vulnerability and “obstruct access” to essential services. The new guidelines address the importance of identifying and trying to overcome structural barriers.  

Dr Meg Doherty, the Director of WHO’s Global HIV, Hepatitis, and STI Programmes commented on recent data from UNAIDS: 

“around 70% of new HIV infections occur among key populations and their partners.” 

She identifies “limited access, inadequate coverage, and poor quality of services” that undermine HIV, hepatitis, and STI responses globally.  

The guidelines also offer recommendations for service delivery, such as online interventions and peer navigators, who will “guide members of key population groups through health services”. Other recommendations include “addressing chemsex”, increasing HCV testing for people at risk of infection, and providing immediate HCV treatment to newly infected patients.  

As data emerge from UNAIDS that reveal Covid-19’s detrimental effect on other health crises these recommendations are timely. Will they have a tangible effect, or will these populations continue to suffer higher infection rates?

Northern Europe’s novel hepatitis nightmare

Northern Europe’s novel hepatitis nightmare

In April 2022, cases of acute hepatitis of “unknown origin” in children were reported across the WHO European Region. Several cases also appeared in the Region of the Americas. In July 2022 the total number of reported cases was at least 1,000 in 35 countries. At least 22 patients have died, and several children have required liver transplants. However, liver transplantation is only possible in a few highly specialised centres, so it is imperative that we identify cases and find an effective treatment.

In an investigation by the University of Glasgow and University College London researches examined samples from 26 children with the hepatitis. Of the 26 samples, 25 children were also infected with the parvovirus AAV2 (adeno-associated virus 2). This is highly contagious but is “not known for causing illness”. Therefore the Glasgow group had to probe further for the answer to this mysterious hepatitis.  

The Economist reported in July 2022 that in 8 of 9 children with the  new hepatitis “they found variations in the Human Leukocyte Antigen gene”. These were “not commonly found in the 58 comparison children”. These variations are geographically concentrated in northern Europe, where the majority of these “strange hepatitis” have been observed.  

The WHO stated that additional work was required to continue identifying cases and determining the cause. In doing so, it hopes to “further refine control and prevention actions”.  

The Lancet described the rise of “conspiracy theories”, which attribute these novel cases to the Covid-19 vaccines. The vaccines have been “categorically ruled out”. Many of the children with the hepatitis were too young to receive a Covid-19 vaccine.  

Our post marking World Hepatitis Day 2022 explores the vaccine solutions to hepatitis available across the world. As a new threat emerges it will be critical that a cause can be identified, and treatment or preventative measures can be implemented, quickly and equitably. So far, the global community has not demonstrated such a practical approach.