GSK awarded malaria vaccine contract by UNICEF

GSK awarded malaria vaccine contract by UNICEF

The pharmaceutical company GSK was awarded a contract for the first supply of a malaria vaccine by UNICEF in 2022. The contract, with a value of up to $170 million, is expected to lead to 18 million doses of a vaccine over the next 3 years.  

According to the WHO, at least 30 countries have “moderate-to-high” areas of malaria transmission. Malaria is one of the “biggest killers of children under 5”. In Africa alone, nearly half a million children died from the disease, with a rate of “one death every minute”.  

The RTS,S malaria vaccine is the world’s first vaccine against a parasitic disease. It acts against Plasmodium falciparum, the deadliest malaria parasite and the most common in Africa. Although approved by the EMA in 2015, there were concerns about the efficacy of RTS,S. However, in 2019 a pilot was launched by the WHO in Ghana, Kenya, and Malawi. The “experience and evidence generated” encouraged the WHO’s recommendation of RTS,S in October 2021.

In December 2021 Gavi elected to provide funding for the malaria vaccine programmes across eligible countries. CEO Seth Barkley reported that the “application window” for funding requests was open, saying “thanks to UNICEF’s procurement” they had “more certainty on supply”. The hope is that “increasing volumes will also lead to more sustainable, lower prices”.  

Etleva Kadilli, director of UNICEF’s supply division, believes that the vaccine rollout “gives a clear message to malaria vaccine developers to continue their work”. She wants to impress upon them that “malaria vaccines are needed and wanted”. Her intention is that “continued innovation” will “increase available supply” and promote a “healthier vaccine market”.  

“This is a giant step forward in our collective efforts to save children’s lives and reduce the burden of malaria”. 

Dr Kate O’Brien, WHO director of the department of immunisation, vaccines, and biologicals, said that the WHO “welcomes the progress” made through this contract. She reflected that “lives are at stake, every day”, and that securing “supply and timely access” will contribute to wider malaria prevention efforts. The demand for the vaccine will be high among affected countries, warned UNICEF. However, with increasing manufacturing capacity supply will increase over time.   

To hear more about progress in malaria vaccines, come to the World Vaccine Congress in October 2022.  

Malawi’s cholera outbreak sustained through winter

Malawi’s cholera outbreak sustained through winter

Malawi’s cholera outbreak in March 2022 came at the end of rainy season. However, as the disease continues to claim lives it is thought that the damage caused by tropical storms is partly to blame. Head of Public Health at Kamuzu University of Health Sciences, Professor Adamson Muula, stated that “climate change” is increasing the “problem”.  

Ministry of Health spokesperson, Adrian Chikumbe, emphasised that access to clean water is central to the outbreak, particularly for Blantyre. “Only 37% of the district’s population has access to safe water”, he said. Despite advising people to “treat their water before usage”, he observed that “many areas are congested” with “no space between wells and pit latrines”.  

According to Chikumbe, the fatality rate is particularly concerning. “The standard is only 1 person per 100 but we have close to 5 fatalities per 100”. Blantyre has suffered 351 cases and 18 deaths so far. Dr Neema Rusibamayila Kimambo, the WHO country representative, says the 4.77% national fatality average needs to be reduced. She identifies “several factors” such as “poor community knowledge” that mean people seek health support too late.  

The local District Environmental Health officer (DEHO), Penjani Chunda, stated that many cases are emerging in “slum townships” with 10- to 29-year-olds worst affected.  

“Even though vaccines are a reactionary approach, in places where vaccines have been administered, we have seen cases slowing down.” 

He is positive about the effect and uptake of vaccines but concerned about the “challenge” of reaching certain areas. Tactics to increase uptake include WhatsApp groups, says Fedson Kansiyamo, Chairperson for Naperi Development Committee.  

“I personally believe in prevention rather than curing a disease, which is why I was one of the first residents to receive the cholera vaccine during the campaign”.  

Kansiyamo believes that poor sanitation is “reversible”. He identifies waste-dumping and “diaper disposal” as significant contributors that need to be addressed.  

Gavi’s report on the situation states that a cholera vaccination campaign launched in May 2022. With support from WHO, Gavi, and UNICEF, Malawi is targeting 1.9 million people. Consequently, the Ministry of Health received 3.9 million doses of oral cholera vaccines from the “global stockpile” funded by Gavi. Professor Muula is grateful for the vaccines; however, they “don’t remove the fact that people are drinking water that is mixed with human faeces”.  

“We should be working towards a country where vaccines are not needed. We need to get back to basics, ensure that our people have safe water for drinking”.  

To hear about recent cholera vaccine technology at the World Vaccine Congress in October 2022 click here to get your tickets.  

Bavarian Nordic capacity increased with US manufacturer

Bavarian Nordic capacity increased with US manufacturer

Bavarian Nordic announced in August 2022 that it had “entered into an agreement” with Grand River Aseptic Manufacturing (GRAM) to expand capacity for the delivery of monkeypox vaccines to the US. GRAM is a US based manufacturer with an FDA approved facility. The US Biomedical Advanced Research and Development Authority (BARDA) has requested 5.5 million doses for 2022 and 2023.  

In July 2022 Bavarian Nordic took an order for 2.5 million doses of the vaccine from BARDA. This will be filled at GRAM using “bulk vaccine already manufactured and invoiced under previous contracts with BARDA”. Bavarian Nordic stated that the tech transfer of the production process has “already been initiated” with the hope of completion within 3 months. This process often takes up to 9 months, and the intention is to enable GRAM to begin manufacturing later in the year.  

Bavarian Nordic emphasised that this increased capacity would “expedite delivery of vials to the US” but also create further opportunities for other countries. Within Denmark it is already operating at “double the capacity” compared to before May 2022. Furthermore, Bavarian Nordic is “exploring additional partnerships” to expand capacity and improve “global access to the vaccine”. This comes amidst increased concern that countries where monkeypox is endemic were not able to access the vaccine. As demonstrated in the Covid-19 pandemic, global vaccine access is a critical component of a coordinated global response.  

The Coordinator of the White House National Monkeypox Response, Bob Fenton, stated that “increasing the supply and safe delivery” of the monkeypox vaccine was a “top priority for President Biden”.  

“This partnership between Bavarian Nordic and GRAM will significantly increase the capacity to fill and finish government-owned doses”. 

Paul Chaplin, President and CEO of Bavarian Nordic, said that the company had been working “diligently” since the beginning of the outbreak. This agreement is an “important step” in allowing Bavarian Nordic to “meet the growing worldwide demand”.  

To hear more about the monkeypox outbreak and ongoing responses come to the World Vaccine Congress in October 2022.

UNITAID’s “Landscape” of tools and strategies

UNITAID’s “Landscape” of tools and strategies

UNITAID published a report in August 2022 to examine the “landscape of tools and interventions” to prevent mother-to-child transmission of HIV, syphilis, hepatitis B, and Chagas. Mother-to-child transmission is also known as vertical transmission. The report identifies this as a target to “accelerate progress towards global elimination goals”. In this article we examine the role of vaccination in the report, and in the wider context of the WHO’s “Triple Elimination” agenda. 

The “Triple Elimination” agenda “seeks to encourage countries to pursue an integrated and coordinated approach to eliminating vertical transmission of HIV, syphilis, hepatitis B, and in countries where it is endemic, Chagas”. UNITAID’s report explores the current challenges that we face in tackling vertical transmission and identifies “new, emerging, or underutilised products and interventions”.  

As part of the WHO’s three 5-year interlinked global strategies against HIV, syphilis, and hepatitis B, several ambitions were set out: 

  • Zero new HIV infections among children by 2020; 
  • A 30% reduction in new cases of chronic HBV infection by 2020; 
  • <50 cases of congenital syphilis per 100,000 live births in 80% of countries. 

The report states that “none” of these targets was achieved. Thus, an “updated and unified” strategy was required. How, in this most recent publication, is vaccination factored into the global strategy? 

The report states that the “cornerstone of hepatitis B prevention is vaccination”. As we discuss in our article for World Hepatitis Day 2022, there is currently an effective vaccine against hepatitis B. UNITAID suggests that the childhood HBV vaccine series is “highly effective at preventing acquisition of infection during childhood”. Although acknowledging “gaps”, the report highlights that there is an 85% global coverage of the “3-dose infant HBV immunisation series”.  

“In sub-Saharan Africa, vaccination was found to be the most cost-effective intervention to reduce perinatal HBV infection rates.” 

However, the report states that “childhood vaccination alone cannot achieve elimination goals” as perinatal transmission is a “growing proportion” of new infections. As other strategies are considered, the report also emphasises the need to accelerate advances in vaccine technology. Possibilities include “prefilled auto disposable devices to deliver accurate birth dosage and remove cold chain barriers”. This technology, UNITAID suggests, will be “more cost effective with minimum wastage”.  

Despite WHO encouragement of re-labelling the hepatitis B vaccines “for use in a controlled temperature chain (CTC), no prequalified product” has been made available. However, there are updates to traditional technology that are worth highlighting. Uniject, a “1-dose pre-filled auto disabled disposable syringe” is one such update. This is simple to use and is recommended for “outreach settings”.  

The report suggests that new technologies are needed, both on a diagnostic front and vaccine front. Innovations include “easier methods of vaccine delivery” and “less restrictive cold chain requirements for vaccine storage and delivery”. As we move ever closer to 2030’s target of elimination, innovation is needed more than ever.  

For more information on vaccine technology for hepatitis and HIV come to the World Vaccine Congress in Europe 2022.  

UK’s first human Brucella canis case confirmed

UK’s first human Brucella canis case confirmed

The European Scientific Counsel Companion Animal Parasites (ESCCAP) called for compulsory testing of imported dogs after the UK’s first case of dog-to-human transmission of Brucella canis (B canis). This causes an infectious disease called canine brucellosis, with a variety of reproductive consequences for both sexes. For female dogs, abortion and failure to conceive are common. For male dogs, abnormal semen quality and painful testicles are likely. Both sexes might experience lethargy, weight loss, and lameness.  

The UK’s first dog-to-human transmission was recorded when a rescue dog from Belarus infected her owner. Moosha, a German shepherd cross, began to abort her puppies three days after arriving at her new foster home. The initial fear was that Moosha had rabies, but she was diagnosed with canine brucellosis two months later. Eventually her owner contracted the disease and was hospitalised. All four of her dogs had to be euthanised as three contracted the disease and the fourth was at high risk. This case represents both the first dog-to-dog transmission and the first dog-to-human transmission recorded in the UK. 

Dr Ian Wright, Guideline director for ESCCAP, stated that “the zoonotic risk is low but as this case demonstrates, very real.” 

“Ideally, testing should be compulsory for dogs being imported into the UK from endemic countries” 

He outlined the key signs that veterinary professionals should be aware of: “vets, nurses, and owners should also be aware of relevant clinical signs in imported dogs. These include infertility, abortion, endometritis, epididymitis and orchitis, and scrotal oedema.” 

A spokesperson for Defra stated that it was working closely with the UKHSA to “ensure all those in contact with this shipment of dogs were aware of the associated human and animal health risks”. The spokesperson emphasised that “strict checks” are in place, including a requirement for rabies vaccination and “relevant tests or treatments prior to travel”.  

To participate in veterinary science discussions at the World Vaccine Congress in Europe this year, buy your tickets here.
 

WHO updates guidance for Tuberculosis response

WHO updates guidance for Tuberculosis response

In August 2022 the WHO announced new guidance to “support national strategic planning” for tuberculosis (TB) responses. This guidance was described as a culmination of the “latest WHO guidelines” by Dr Tereza Kasaeva, Director of WHO’s Global Tuberculosis Programme.  

“It highlights the importance of comprehensive and inclusive engagement of relevant stakeholders and partners”.  

This guidance was produced to “better align with global commitments” and recent developments in TB and public health. It updated the 2015 “Toolkit” to provide a “national strategic plan for TB prevention, care, and control.” A national strategic plan (NSP) “guides the national TB response through interventions within and beyond the health sector”. It does this by identifying priorities for health authorities and stakeholders and how these can be coordinated across “various sectors”.  

“The NSP translates global, regional, and national commitments into national and subnational targets and activities to be implemented to achieve these targets and provides the basis for mobilisation of domestic and external resources”.  

The foreword to this guidance states the global intention of reducing TB deaths and incidence by 90% and 80% respectively from 2015 to 2030. Among the means of achieving this are a “commitment to ambitious targets for TB treatment and prevention”.  

Within the guidance is a table of “Pillars, principles and components of the end TB strategy”. This comprises four pillars: 

  1. Government stewardship and accountability, with M&E. 
  2. Strong coalition with civil society organisations and communities. 
  3. Protection and promotion of human rights, ethics, and equity. 
  4. Adaptation of the strategy and targets at country level, with global collaboration. 

The pillars and components are as follows: 

Integrated, patient-centred care and prevention: 
  • Early diagnosis of TB including universal DST and systematic screening of contacts and high-risk groups. 
  • Treatment of all people with TB including drug-resistant TB, and patient support. 
  • Collaborative TB/HIV activities, and management of comorbidities. 
  • Preventative treatment of people at high risk, and vaccination against TB. 
Bold policies and supportive systems: 
  • Political commitment with adequate resources for TB care and prevention. 
  • Engagement of communities, civil society organisations, and public and private care providers. 
  • UHC policy, and regulatory frameworks for case notification, vital registration, quality and rational use of medicines, and infection control. 
  • Social protection, poverty alleviation, and actions on other determinants of TB. 
Intensified research and innovation: 
  • Discovery, development, and rapid uptake of new tools, interventions, and strategies.  
  • Research to optimise implementation and impact and promote innovations.  

Dr Tereza Kasaeva will be speaking at the World Vaccine Congress in Europe in October 2022; get your tickets to the Congress here.  

UK’s JCVI updates Covid-19 booster programme

UK’s JCVI updates Covid-19 booster programme

In August 2022 the UK’s Joint Committee on Vaccination and Immunisation (JCVI) published advice on the boosters that will be used for each group in autumn. The JCVI emphasised that every option on the list provides protection against “severe illness” from Covid-19. Furthermore, the Committee highlighted the need to get a booster before winter.  

For adults 18+: 
  • Moderna mRNA (Spikevax) bivalent Omicron BA.1/Original ‘wild-type’ vaccine 
  • Moderna mRNA (Spikevax) Original ‘wild-type’ vaccine 
  • Pfizer-BioNTech mRNA (Comirnaty) Original ‘wild-type’ vaccine 
  • Novavax Matrix-M adjuvanted wild-type vaccine (Nuvaxovid) “may be used when no alternative clinically suitable UK-approved COVID-19 vaccine is available” 
For young people 12-17: 
  • Pfizer-BioNTech mRNA (Comirnaty) Original ‘wild-type’ vaccine 
For children 5-11: 
  • Pfizer-BioNTech mRNA (Comirnaty) Original ‘wild-type’ vaccine paediatric formulation 

Professor Wei Shen Lim, Chair of Covid-19 immunisation for the JCVI, stated that “all of the available booster vaccines offer very good protection against severe illness from Covid-19″. 

“It is important that everyone who is eligible takes up a booster this autumn, whichever vaccine is on offer.” 

Dr Mary Ramsay, Head of Immunisation at UKHSA, suggested that although cases were “relatively low at present” she expected to see an increase in circulation “during the winter months”.  

To hear from speakers from Moderna, Pfizer, and Novavax at the World Vaccine Congress in Barcelona 2022 click here to get your tickets.  

White paper from IDT Biologika: oncolytic viruses

White paper from IDT Biologika: oncolytic viruses

In a white paper for IDT Biologika Dr Heidi Trusheim and Trevor Broadt examine the process of developing oncolytic viruses and how to avoid problems. Oncolytic viruses (OVs) have the “potential to revolutionise standard cancer treatment”. Researchers continue to “pursue the optimisation of these viruses” through engineering strategies, but Dr Trusheim and Broadt suggest that progress relies on the achievement of several goals. These are related to “safety, efficacy, and commercial scale-up”. The first oncolytic to receive FDA approval was in 2015, and since then the “need for contract development and manufacturing organisation (CDMOs) with experience in viral vector design” has become more pressing.  

How to avoid the “pitfalls of oncolytic virus design” 

OVs are so exciting to the industry because they have two “primary modes of action”: 

  1. They can kill infected cancer cells 
  2. They can stimulate cross-primes cancer immunity to “boost the killing of uninfected cancer cells”. 

Thus, they offer great improvement potential to current cancer therapies. Recent research focuses on equipping OVs with a range of transgenes to “increase their immune stimulation, modulate immune checkpoints, and provide imaging targets”. The basic science at the “core” of OV immunotherapy is over a century old. However, more recently it has been applied to a range of engineered viruses. Unfortunately, limited development capabilities mean that “only a few adenovirus-based oncolytic therapies have been approved by regulators”. Despite this developmental drawback, many are in development or at clinical trial stage. 

One of the key reasons for the slow development is the need to ensure the “relative safety of the viral vector”. The “foremost consideration” for early clinical trials is “minimising the potential for viral replication in health cells”.  

Another “variable” is preventing the non-retroviral OVs from “integrating into the host’s genome”. The chance of “random recombination” is another factor to be tested. Dr Trusheim and Broadt emphasise the importance of research into the transgene incorporated in viral vectors, to “eliminate the potential for homologous sequence recombination”. 

“reducing or eliminating the potential for unforeseen scenarios often comes down to fundamentals” 

Partnering for expertise at all levels 

Dr Trusheim and Broadt insist that “vetting” a partner “comes down to the basics”. Unless this process is thorough, the scale-up can be delayed. They suggest identifying a manufacturing partner with a “proven track record” or design and manufacturing. Furthermore, partners should understand the “primary challenges that plague oncolytic virus design”.  

“Because only a handful of oncolytic viral therapies exist on the market today, the regulatory environment surrounding them is still relatively fluid.” 

Partners should have experience in “engaging with regulators” and “interpreting regulatory guidance”. IDT Biologika, for example, has a “well-codified” approach to scale-up. End-to-end development is enhanced by tailored facilities and equipment. So far in the past year IDT Biologika has successfully supported the development of viral vector applications including pox viruses, adenoviruses, and measles virus.  

“IDT’s experience in optimising not just the cell line and passage range, but the media and viral harvest conditions, offers customers the latitude to pursue these under-explored, highly transformative therapies with more confidence.”

To hear from IDT Biologika’s Senior Vice President of Development, Dr Simone Kardinahl, at the World Vaccine Congress in Europe 2022 click here for tickets.  

For the full paper by Dr Trusheim and Broadt, click here to download a copy.  

 

mRNA vaccine for cancer shows promise at Tufts University

mRNA vaccine for cancer shows promise at Tufts University

A study in PNAS in August 2022 presented an mRNA vaccine for cancer that targets the lymph nodes instead of the liver. Researchers at Tufts School of Engineering believe that this method is “so strong and precise, it eliminates tumours and even prevents their recurrence”.  

This vaccine delivers mRNA in small lipid bubbles that fuse with cells that can then produce viral antigens. Specifically, the lipid nanoparticles (LNPs) “zero in on the lymphatic system”. The team created LNPs that “favoured delivery to the lymph nodes over the liver by a three-to-one ratio”. Professor Qiaobing Xu stated that “targeting the lymphatic system helped us to overcome many of the challenges that have faced others in developing a cancer vaccine”. He and his colleagues have previously targeted LNPs to the brain and liver, as well as the lungs. 

Tufts reported that over 20 mRNA cancer vaccine candidates have progressed to clinical trials, but “usually much of the mRNA ends up in the liver”. On the other hand, in the lymph nodes, the vaccine was “absorbed by about a third of dendritic cells and microphages”. This produces more B and T cells, which in turn cause a stronger immune response.  

Mice with metastatic melanoma demonstrated “significant inhibition of tumours and a 40% rate of complete response” when treatment was “combined with another existing therapy”. Furthermore, the cancer vaccine prevented additional tumour formation, suggesting “excellent immune memory”.  

Postdoctoral researcher fellow, Dr Jinjin Chen, stated that “cancer vaccines have always been a challenge”. This is because the tumour antigens don’t appear as “foreign” to the body and the tumours can inhibit the immune response.  

“This cancer vaccine evokes a much stronger response and is capable of carrying mRNA for both large and small antigens” 

The hope is that this vaccine will become a “universal platform” for effective vaccines against more viruses and other pathogens as well as cancers.  

To get updates on cancer vaccine technology at the World Vaccine Congress in October 2022 click here for your tickets. 

Avian influenza restrictions lifted in the UK

Avian influenza restrictions lifted in the UK

In August 2022 the UK’s Chief Veterinary Office, Professor Christine Middlemiss, appealed to bird keepers to maintain enhanced biosecurity measures after an avian influenza outbreak. Restrictions lifted on 16th August, but Professor Middlemiss is keen to ensure that people remain vigilant. 

In November 2021 authorities implemented an avian influenza prevention zone (AIPZ) across Great Britain. This required bird keepers, from keepers of poultry or pets to commercial flocks, to take “additional biosecurity precautions”. Further restrictions enforced this with a requirement to keep birds housed from November 2021 to May 2022.  

The Department for Environment, Food, and Rural Affairs (Defra) warned of the UK’s largest ever flu outbreak. Over 130 cases have been confirmed since October 2021. Professor Middlemiss emphasised that although the restrictions had been lifted, bird keepers should continue to follow “enhanced measures”.  

“Now we are in the summer months and experiencing higher temperatures, the risk to poultry has now been reduced…the time is right to lift the [AIPZ].” 

She thanked all bird keepers for their “hard work” in upholding “high biosecurity standards for many months”. However, she reminded keepers of “localised areas of risk”. Furthermore, she insisted that it is “vital that everyone keeps biosecurity and cleanliness at the forefront of their minds to keep their flocks safe”. If members of the public or keepers suspect disease they are advised to contact the Defra helpline.

Vaccination

As of 2021 the government continues to advise against vaccination of “poultry and most captive birds”.  

“Vaccination is not a routine control measure and is a practice restricted by legislation.” 

Among the reasons stated against vaccination, the government cites transmission of avian influenza from vaccinated birds. Additionally, influenza viruses “mutate rapidly, which could render a vaccine less useful”. Handling and welfare implications for the birds are also suggested difficulties.

The government states that “early reporting, rapid action, biosecurity, culling, and surveillance remain the most effective” means of prevention.  

To participate in discussions on avian influenza at the World Vaccine Congress in Europe 2022, click here for tickets.  

UK approves Moderna’s dual vaccine against Covid

UK approves Moderna’s dual vaccine against Covid

The UK Medicines and Healthcare products Regulatory Agency (MHRA) announced in August 2022 that it approved Moderna’s bivalent vaccine, Spikevax Bivalent Original/Omicron, against two forms of Covid. Dr June Raine, chief executive of the MHRA, stated that the “first generation” vaccines “continue to provide important protection against the disease”. However, the candidate presents exciting opportunities for the UK. 

“What this bivalent vaccine gives us is a sharpened tool in our armoury”. 

The UK is the first to approve the dual vaccine, which targets the original virus and the newer Omicron variant. It is predicted to be available during the autumn as a booster, and we can expect 13 million doses by the end of the year. Moderna will begin supplying doses in the next few weeks. The vaccine also awaits approval in Australia, Canada, and the EU. 

In June 2022 Moderna announced that the vaccine was safe. It also offered a “superior antibody response” in trials. The dose “increased neutralising geometric mean titers against Omicron approximately 8-fold above baseline levels.” Furthermore, it “elicited potent neutralising antibody responses against the Omicron subvariants”.  

Stephane Bancel, CEO of Moderna, is “delighted” at the approval of the vaccine.  

“This represents the first authorisation of an Omicron-containing bivalent vaccine, this bivalent vaccine has an important role to play in protecting people in the UK”. 

The UK government’s independent science advisory body also approved the vaccine. Professor Sir Munir Pirmohamed, chair of the Commission on Human Medicines, reported that the Commission “independently reviewed the data” and agreed with the decision taken by MHRA.  

“This novel bivalent vaccine represents the next step in the development of vaccines to combat the virus”. 

Moderna will partner with The Vaccine Taskforce, UKHSA, and the NHS, to make the vaccine available in the UK. However, we will need to see further action to share the vaccine more widely if it is to have a tangible effect. 

To hear from speakers from Moderna at the World Vaccine Congress in Europe 2022 follow the link to get your tickets.  

University partners find MND therapy potential

University partners find MND therapy potential

In August 2022, researchers announced evidence that Terazosin “protects against the death of motor neurones”. This is a step towards an effective therapy for motor neurone disease (MND). The study, published in eBioMedicine, used funding from MND Scotland and the My Name’s Doddie Foundation. It was the result of a partnership between the University of Edinburgh and the University of Oxford

Professor Kevin Talbot of the Nuffield Department of Clinical Neurosciences emphasised the need to “accelerate the way drugs are developed”. His team’s work combines approaches “to increase confidence” in drugs that slow disease progression. 

“It represents an important new step in the search for therapies.” 

MND is a rapidly progressing illness that weakens communication between the brain and the muscles. It affects around 5,000 adults in the UK. The average life expectancy is 3 years from the onset of symptoms. The chances of an adult getting MND are 1 in 300. As there is not cure for MND this research is particularly exciting. Although it is unclear why motor neurones die, experts know that a “decrease in energy” occurs at an early stage of the disease. Without energy, messages do not transmit between the brain and the muscles. This results in impaired movement.

Terazosin targets enlarged prostates or high blood pressure. However, it is also known to increase energy production in “models of stroke and Parkinson’s disease”. This research focused on an enzyme called PGK1 and found positive results in zebrafish, mice, and stem cell models. Next, the team will invite 50 patients from the Oxford MND Care and Research Centre to take part in a feasibility study.  

Dr Jane Haley MBE of MND Scotland is “delighted” at the prospect of a feasibility study. She praised this collaboration as a “wonderful example” and hopes that it will provide a step towards a cure.  

To participate in discussions about life-changing therapies at the World Vaccine Congress in Europe, 2022, click here for tickets.

White paper from IDT Biologika: oncolytic viruses

White paper from IDT Biologika: viral vectors

In a white paper for IDT Biologika Dr Andreas Neubert explores how viral vectors offer a host of opportunities for vaccine development with the right conditions and collaboration. He describes the expanding “conversation” around vector-based treatments over the last 20 years. Since their development two decades ago, he states that their “value has become more apparent”. They present opportunities for both prophylactic and therapeutic treatments, yet “many drug manufacturers still do not have the means to scale up their production”. Thus, companies must use contract development and manufacturing organisations (CDMOs). 

Special needs 

Dr Neubert reflects that among the “many hurdles” involved in driving vector-based treatments to market, a significant challenge is “access to the necessary facilities and equipment”. Production of vector-based therapies relies on “access to cell lines, cell characterisation and analysis resources, cell propagation in cell factories, and fermenting systems”. Expertise is essential to scaling up viral vectors, to create systems for “optimal yields and potency as well as safety”. 20 years ago, when vectors emerged, the “standard equipment” for vaccine production was stainless steel. According to Dr Neubert this doesn’t provide the necessary flexibility. Single-use technology (SUT) “affords greater flexibility”, he states, but is expensive and often “fails to meet the scale and standards” required.  

Further requirements relate to the consequences for patients: “when characterising cells lines, developers must ensure that they contain no indigenous or adventitious viruses, no tumorigenicity, and no potential to cause harm in patients”. Dr Neubert insists on the importance of “functional” vectors that “carry no microbiological or viral contamination”. The equipment used for manufacturing must be “reliable’ and perform accurately.  Each step of the process brings more complications. For example, “fermentation and purification steps” can “adversely affect virus propagation”. Highly specialised conditions are also necessary for freeze-drying or storage, even the final manufacturing processes.  

Understanding is vital 

Although he recognises the speed of the development of Covid-19 vaccines “seems remarkable”, Dr Neubert considers it to be “on par with the standard rate of development”.  

“The science behind the vaccines now on the market began about 10 years ago” 

Evolving tools and technologies enable us to keep up with increasing knowledge to develop vaccines. In contrast to traditional vaccines, which often contain elements that “suppress or modify” immune responses, viral vectors are “well-known to be safe in humans”. They also provide “more options for eliciting a specific reaction”.  

As well as prophylactic solutions, viral vectors have potential for gene therapy. In these cases, vectors with “low immunogenicity” are used. Dr Neubert recognises that the current state of viral vector knowledge “emerged from setbacks as much as successes”. However, it is also a result of IDT Biologika’s “collaboration with partners and customers across the world”, he says. 

“IDT Biologika has worked since 1997 to help numerous companies and academic institutions develop vector-based products”.  

Partnerships promote learning 

IDT Biologika works with partners in across the industry to “design and improve the specialised spaces and systems” needed to manufacture and scale up. A current challenge is the development of a vector-based vaccine against Covid-19. Hoping to reduce side effects and increase immunity, the developers are using a vector that has been “proven safe in humans for nearly 20 years”. As well as design and development, IDT Biologika provides “guidance and support” to partners.  

Dr Neubert’s conclusion 

Although viral vectors have been around for two decades, their “potential applications are still largely unexplored”. This presents the industry with room for further research and development, despite the complex nature of managing the products. Dr Neubert reflects that equipment and expertise are necessary, recalling the importance of partnerships. However, the most important factor for success in his mind is “a spirit of collaboration and a willingness for developers, manufacturers, researchers, and CDMOs to learn together and build upon their shared experience to advance this exciting science”.  

To hear from IDT Biologika’s Senior Vice President of Development, Dr Simone Kardinahl, at the World Vaccine Congress in Europe 2022 click here for tickets.  

For the full paper by Dr Neubert, click here to download a copy.  

Study reveals Covid-19 vaccinations safe for pregnancy

Study reveals Covid-19 vaccinations safe for pregnancy

A study published in The Lancet in August 2022 concluded that Covid-19 vaccinations had a “good safety profile” for pregnant people. This was concluded during an attempt to “determine the frequency and nature of significant health events among pregnant females after Covid-19 vaccination”. The “observational cohort study” was conducted across Canada as part of the Canadian National Vaccine Safety (CANVAS) network study.  

The Covid-19 pandemic “disproportionately affected pregnant people” according to the investigators, who explored out higher risks of hospital admission, intensive care unit admission, requirement for ventilation, and death. Furthermore, infection also “increases risk of adverse pregnancy outcomes”, which include impaired foetal growth or preterm birth. In a previous article we explored some of the reasons behind low maternal immunisation rates, suggesting that a lack of data complicated public health communication. Thus, this research is an important step in encouraging pregnant people to come forward when vaccines are available to them.  

Overall, “pregnant vaccinated females had a decreased odds of a significant health event compared with non-pregnant vaccinated females” after both doses of “any mRNA vaccination”. One of the most pressing concerns among pregnant women might be miscarriage or stillbirth, as the most “frequently reported adverse pregnancy outcome”. However, this was “reported at similar rates” between the control group and the vaccinated group. Additional outcomes such as bleeding or reduced foetal movement were “rarely reported” following mRNA vaccination.  

The authors of the study acknowledge the strengths and limitations of their results. One such limitation is that CANVAS is “based on self-reports” and does not feature specific medical verification. This is highly subjective but has been “shown to be reliable for short time periods”. Further limitations can be found in the profile of patient selected, as an email address was required and fluency in French or English was also a prerequisite. 

Despite the handful of limitations, the data provide “reassuring evidence” that mRNA vaccines are “safe in pregnancy”. The study recommends “high vaccine coverage” to protect both pregnant individuals and their infants. Going forward, further research will be required to demonstrate longer-term data.  

Dr Flor Munoz wrote in 2021 that it is “imperative to better understand the potential of immunisation during pregnancy”.* She insisted on data collection to answer the multitude of questions about immunity in pregnancy and beyond. This study is a step in the right direction towards providing the pregnant community with detailed, accurate information on the benefits of receiving vaccines.  

*Dr Flor Munoz-Rivas led the World Vaccine Congress maternal immunity workshop in Washington 2022. To book your place at the congress in 2023 click this link. 

CEPI driving research into monkeypox vaccines

CEPI driving research into monkeypox vaccines

In July 2022 CEPI announced that it would provide $375,000 to the MHRA and UKHSA to “support the development of key laboratory tools to advance and standardise assessment of vaccines used to protect against monkeypox”. Dr Richard Hatchett, CEO of CEPI, expressed a desire to invest in “tools to support the array of potential developers”. He stressed the importance of “early actions” in pushing research and development forward in line with fast-moving diseases.  

Monkeypox, declared a PHEIC, continues to spread globally with increasing demand on a limited supply of vaccine doses. CEPI’s contribution will go towards assays and a “reference antibody standard”. This is intended to “harmonise how different laboratories assess the strength and duration of immune responses” to current and developing vaccines. The goal is to make these tools “freely available”, except for admin fees.  

CEPI states that assays would enable scientists to “determine whether or not a vaccine has generated an immune response”. Following this, an antibody standard would provide an insight into “whether that antibody response provides a sufficient level of protection against the current circulating monkeypox strain.” 

“Data generated from their use will help to inform current vaccine development and deployment strategies, while also supporting the development and evaluation of monkeypox diagnostics.” 

This funding is part of CEPI’s “Transform pillar” of pandemic preparedness. This “seeks to invest and scale critical enabling programmes to further accelerate vaccine development and deployment”.  Although monkeypox vaccines are already licensed in some countries, deployment has been ineffective so far. Furthermore, as we explored in a previous article, “more data are needed” to demonstrate the protection afforded in human populations.  

Dr Isabel Oliver, Chief Scientific Advisor at UKHSA, is relying on “international cooperation” to develop tools against monkeypox. She stated that “accurate testing and strong surveillance” will be needed to monitor the efficacy of vaccines and “inform public health policy”.  The pressure is on to use this investment to develop a swift and effective approach.

To hear from speakers at CEPI at the World Vaccine Congress in Europe 2022 click here to get tickets! 

Professor Hotez warns against anti-vaccine activism

Professor Hotez warns against anti-vaccine activism

In August 2022 Professor Peter Hotez of the Centre for Vaccine Development at Texas Children’s Hospital wrote an article in Nature exploring the dire consequences of America’s “anti-vaccine activism”. If Professor Hotez’s name is unfamiliar, a twitter search will reveal him to be a highly respected and hugely empathetic source of vaccine information in the face of abuse and misinformation. 

Professor Hotez begins his article with a reflection that “declining immunisation rates” across the world are being driven in many cases by anti-vaccine movements. He considers his own home of Texas, the source of a “false assertions linking vaccines to autism”. Further to these assertions, a “libertarian framework of health freedom” is promoted by elected officials, and he identifies the links between far-right movements and anti-vaccine beliefs.  

Health freedom might sound like a reasonable expectation to many, but Professor Hotez unpacks it for us to explore its more worrying tenets. These do not correlate to the “principles” identified by a health freedom organisation but are a summary of some of the core beliefs. For readers of these “principles”, emotive language such as “hope” and “healing” effectively mask undercurrents of scientific ignorance or denial.  

The effects of anti-vaccine activism’s security within “health freedom” are “tragic and even deadly”. Since 2021, “200,000 unvaccinated” Americans have died. Professor Hotez reflects on analyses that show these deaths and low vaccination rates are “overwhelmingly along a partisan divide and in Republican-majority states”. Health, as always, is a deeply political issue.  

However, Professor Hotez’s concern is that this anti-vaccine movement is “now linked to health freedom politics” that have enabled greater “anti-vaccine sentiment in other countries”. Hence “freedom convoy” protests in Canada, and anti-vaccine rallies across Europe. This has further consequences for routine vaccinations, which are reportedly dropping. The effect on LMICs is another troubling concern for Professor Hotez. He states that “tremendous strides” have been made against measles, polio, pertussis, and other “dangerous illnesses” against which we have effective vaccines. Anti-vaccine movements pose a threat to this progress.

The WHO has long identified “vaccine hesitancy” as a top ten global health threat, and as routine childhood vaccinations are “backsliding”, this is more pertinent than ever. Alongside this, Professor Hotez acknowledges that “access accounts for most of the vaccine inequality”. Although “evidence that links US anti-vaccine activism to vaccine refusal in LMICs remains fragmented and often elusive” it does emerge. Professor Hotez states that anti-vaccine materials, memes as well as more structured resources, “circulate widely”. This international reach of social media “disproportionately” provokes vaccine hesitancy according to the African CDC.  

“Confirming the adverse impact of American Covid-19 anti-vaccine activism is challenged by the paucity of culturally relevant on-the-ground reporting and the fact that data are often unsearchable in the biomedical science literature.” 

However, these “activists” are increasingly turning their attention to vaccines other than the Covid-19 vaccines. Among the “disinformation dozen” is a US-based organisation “claiming a tetanus immunisation programme is a WHO ‘population-control experiment’ that sterilised African women”. Further attacks include “claims around injuries as a result of polio and other vaccine campaigns in India and elsewhere”.  

Hotez’s conclusion is that vaccine refusal must not be permitted to permeate borders and must be addressed within the US. His recommendations include exploring “anti-vaccine activities in LMICs” and creating an “observatory for collecting and analysing disinformation”. Further to this, he suggests seeking support external to the US to address internal movements.  

“We must recognise the depth and breadth of anti-vaccine activism and its detriment to global security”.  

To hear from Professor Peter Hotez at the World Vaccine Congress in Washington 2023, click here to get your tickets.  

Langya (LayV) henipavirus emerges in China

Langya (LayV) henipavirus emerges in China

Langya (LayV) is a henipavirus, the genus that includes the Hendra and Nipah viruses. According to an article in New Scientist it appears to be “most closely related to Mojiang henipavirus”, which was linked to the onset of severe pneumonia and death in three men in 2012. The virus was discovered when a group of patients with fever and a “recent history of animal exposure” were monitored in Eastern China. LayV was identified in a throat swab from one of these patients.  

Later analysis revealed that 35 known cases of LayV have been detected in the Shandong and Henan provinces of China between 2018 and 2021. No evidence of human transmission has been found so far, but the sample size is too small to rule this out. Researchers tested 25 species of animals and found 27% of the 262 shrews surveyed had “detectable levels of LayV”. This suggests that the natural reservoir may be shrews. 

Dr Olivier Restif of the University of Cambridge stated that LayV is unlikely to spread between people: 

“I don’t think this has much pandemic potential.” 

As so few cases have been detected over recent years, researchers are not seriously concerned about transmission. Professor Francois Balloux of University College London states echoes Dr Restif’s sentiment: 

“The virus is unlikely to be something that passes from person to person easily and can easily cause an epidemic or pandemic.” 

However, he does predict that the “most likely source” of future pandemics will be zoonotic spillover. He warns that we must be better prepared for another episode in the “coming decades”. The CDC estimates that 3 out of 4 new or emerging diseases in people will come from animals. The UN has also warned that climate change and wildlife exploitation will lead to an increase in such diseases.  

To join experts in discussing future pandemics at the World Vaccine Congress in Europe 2022 click here to get your tickets!

The monkeypox vaccine: how much do we know?

The monkeypox vaccine: how much do we know?

As monkeypox cases across the world continue to increase, rollouts of the one licensed vaccine are under pressure. In the UK, questions about the number of doses were posed in a letter written by LGBTQ+ groups. In the US, NIH scientists have started to explore “fractional dosing”. The Modified vaccinia Ankara (MVA) that was previously licensed for monkeypox in Canada and the US has been approved by EU counterparts. However, in August 2022, an article in Science called into question the longevity and efficacy of the vaccine. The author, Kai Kupfershmidt, explored the options going forward.  

Originally developed by Bavarian Nordic as a smallpox vaccine, MVA is known to help against monkeypox. Yet “ethical and logistical complexities” of the current crisis are making it hard to establish how much protection it provides. It is difficult to execute “placebo-controlled clinical trials” as the vaccine is already licensed and demand is high.  

Initial evidence that smallpox vaccines might protect against monkeypox emerged in a study in the 1980s. It appeared that smallpox vaccination was “86% effective at preventing monkeypox” among contacts of patients with monkeypox in the Democratic Republic of Congo. As the study was limited, MVA was developed as a “safer alternative” to the older vaccine. Although it was licensed, “its efficacy has barely been tested in people”. Furthermore, its role in “preventing sexual transmission” has not been explored.  

The recommendation of a randomised trial is “ethically dicey”. Therefore, other options must be explored. One cohort in France is using MSM “already enrolled in a study of sexually transmitted diseases – and deemed at high risk of monkeypox”. They will get MVA in the next 2 months, and the researchers will compare infection rates either side of vaccination. A “test-negative” study is also under consideration. This involves investigation of people getting tested for monkeypox, comparing the numbers of vaccinated patients among the positive and negative groups. Dr Michael Marks, of the London School of Hygiene and Tropical Medicine, suggests that this is “probably the strongest nonrandomised approach”.  

Unfortunately, this approach requires “good linkage between testing and vaccination data”. Furthermore, these data can’t demonstrate immunity over time, or “whether disease severity is different among the vaccinated and unvaccinated”.  

Dr Will Nutland, co-founder of Prepster, suggests that these unanswered questions will continue to complicate messaging to high-risk groups. However, he wants to impress upon everyone the importance of getting vaccinated.  

“It is better to receive some level of protection than no protection at all.”  

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

Tired T-cells need TLC to continue fighting cancer

Tired T-cells need TLC to continue fighting cancer

T-cells are known to get “exhausted” when fighting cancer. Early exhaustion can sometimes be reversed with immunotherapy drugs, but until now it was believed that this had limits. Genengnews.com reports that recent studies by University of Pittsburgh and University of Pittsburgh Medical Centre (UPMC) indicated the possibility of reviving “the most fatigued T-cells”.  

The researchers “profiled molecular features” of the cells as they moved from “early to terminal exhaustion”. The team noted that “differentiation to exhaustion is progressive”. It is represented by “at least two transcriptionally and functionally distinct states: one progenitor or stem-like and another terminally differentiated”.  To their surprise, the results suggested that terminally exhausted T-cells could “be functional again”.   

Dr Amanda Poholek of Pitt’s School of Medicine and the UPMC Children’s Hospital of Pittsburgh stated that these findings “have incredible potential for immunotherapy”. Providing T-cells with “rest” can enable them to “come back”.  

Currently some cancer immunotherapies can reverse exhaustion, giving T-cells a boost. Unfortunately, terminally exhausted cells do not usually respond to these therapies. However, the team is optimistic that understanding of the “transition from progenitor T-cells to terminal exhaustion”, will promote further advances. Despite this hope it is “unclear” if these cells have “therapeutic potential to gain effector capacity”.  

Co-senior author, Dr Greg Delgoffe of the UPMC Hillman Cancer Centre, stated that in order to “bring the promise of immunotherapy” to more people, scientists need to better understand the process of failure in T-cells. With this goal, the researchers profiled the cells’ epigenome and were “really surprised” to discover that they had “the potential for recovery”.  

In these cells it became apparent that something was “inhibiting gene expression”. They identified that “terminally exhausted T-cells had insufficient co-stimulation”. When addressed with an antibody that binds to a co-stimulatory receptor, 4-1BB, “gene expression increased”.  

Further investigations revealed that hypoxia, “common in the tumour microenvironment”, also influenced gene expression. Thus, when programmed to resist hypoxia, the cells “differentiated into a more functional state”.  

“Our data highlight the convergence of both immunologic signals and pathologic environmental signals that redirect differentiation to exhaustion” 

Dr Delgoffe believes that “restoring oxygen or improving co-stimulation” will push these cells to their “full potential”. The paper concludes with the hope that new approaches could “target hypoxia or co-stimulation pathways”. The ambition is to contribute to therapies that “take full advantage of all subsets of tumour-infiltrating T-cells to eradicate cancer cells”.

To hear about developments in the fight against cancer click here to secure tickets to the World Vaccine Congress in Europe, 2022.

Pan-coronavirus vaccine hopes boosted by cold immunity

Pan-coronavirus vaccine hopes boosted by cold immunity

Scientists at La Jolla Institute for immunology in California have concluded that patients with a stronger immune response to the coronaviruses that cause cold-like symptoms may be “better protected against covid-19″. This offers the hope that a pan-coronavirus vaccine might be within reach. As researchers scramble to find novel methods of providing immunity, these results provide exciting potential. 

An article in New Scientist states that the study analysed blood samples collected before the emergence of covid-19. Multiple samples were collected from each patient over 6 months to 3 years. The team explored the response of the immune cells in these samples to four coronaviruses as well as the SARS-CoV-2 strain. They combined the blood with peptides from the coronaviruses and measured the T-cell and antibody responses that resulted. They found the responses to be “stable and persistent for all four” of the coronaviruses. Furthermore, they established that the immune responses were not due to “regular re-infections”.  

Next, researchers combined the samples with SARS-CoV-2. This revealed that the samples with the stronger T-cell immune responses to the previous four coronaviruses had the strongest response to SARS-CoV-2. However, this wasn’t the same for antibody levels.  

Dr Ricardo da Silva Antunes of La Jolla Institute stated the importance of using pre-pandemic samples. This enabled the researchers to see “pre-existing immune memory”. The genetic similarity of SARS-CoV-2 to the four common cold-like coronaviruses invited the possibility that T-cell responses “induced by prior coronaviruses” might protect against the current SARS-CoV-2.  

Despite these findings, Dr da Silva Antunes says that the “link” between these two categories of coronavirus is “still not clear”. The participants with stronger immune responses to the common cold-like coronaviruses were not guaranteed to experience less severe covid-19.  

For Professor Mala Maini of University College London, these findings add to the growing evidence that T-cell immune responses to common cold-like coronaviruses influence our SARS-CoV-2 responses. She and her colleagues are working towards a pan-coronavirus vaccine. In 2021 she stated that a “vaccine that can induce T-cells to recognise and target infected cells expressing [replication proteins]” might be able to eliminate “early SARS-CoV-2″ as well as “other coronaviruses” that will infect humans in the future.  

To learn about approaches to developing a pan-coronavirus vaccine get your tickets to the World Vaccine Congress in Europe 2022.