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.  

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.  

 

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.  

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! 

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.  

“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! 

Twist Bioscience turns to monkeypox controls

Twist Bioscience turns to monkeypox controls

Twist Bioscience has launched two monkeypox synthetic DNA controls that are estimated to provide 80% coverage of the viral genome. They support the design of “custom assays targeting regions of the genome”. They can also be used for “amplicon and capture-based detection methods”. These controls are “sequence-verified” using next-generation sequencing and droplet digital PCR technologies.  

The Twist controls include both known clades of the virus: the Central African clade and the West African clade. Dr Emily Leproust, CEO and co-founder of Twist Bioscience, reported that the “expanding portfolio of synthetic controls” would “empower our customers…to improve global health”. She stated that Twist would continue responding to emerging public health concerns with research tools.  

Twist is based in San Francisco and delivers a range of research tools and NGS facilities, as well as the “Twist Pan-Viral Panel, which contains over 600,000 probes for the targeted enrichment of over 1,000 viral human pathogens”. These include, but are not limited to, pathogens causing monkeypox and Zika virus.  

Monkeypox was declared a public health emergency of international concern by WHO Director-General Dr Tedros Adhanom Ghebreyesus in July 2022. At that time over 18,000 cases from 78 countries had been reported to the WHO.  

Prioritising pathogens in a pandemic world

Prioritising pathogens in a pandemic world

The WHO list of priority diseases sets out the diseases and pathogens that research and development in “public health emergency contexts” should address. The aim is “focused and productive” research and development. These diseases are evaluated on their epidemic potential alongside countermeasure strength.  

In July 2022 the diseases were: 

  • Covid-19 
  • Crimean-Congo haemorrhagic fever 
  • Ebola and Marburg viruses 
  • Lassa fever 
  • MERS-CoV and SARS 
  • Nipah and henipaviral diseases 
  • Rift Valley fever 
  • Zika 
  • Disease X 

The WHO’s R&D Blueprint was developed at the World Health Assembly in May 2016. It aims to “fast-track the availability of effective tests, vaccines, and medicines”. Identifying “severe emerging diseases” for which there are limited “diagnostic, preventative, and curative solutions”, it unites medical, scientific, and regulatory experts. The Blueprint is established, a list of diseases is regularly curated, and the world watching. What, then, is the strategy to reduce the effects that each of the items on the list can bring? 

In our post on Disease X, we discuss the development of the Pandemic Preparedness and Response Centre and the Global Virome Project’s attempts to understand future risks. Yet these individual examples of initiatives that are pushing the boundaries of our knowledge are few and far between. 

Dr Melanie Saville, Executive Director of Vaccine Research and Development at CEPI, stated in 2021 that “ambition”, united with “sustained commitment and adequate resources” might enable an end to “the spectre of pandemics”.  

“By building on the lessons learned in 2020, it should be possible in the long term to compress vaccine development timelines still further.” 

Although vaccines are the most “powerful tools” we have against this list of diseases, Saville wants the public to know that the historic achievements of the Covid-19 response were not “out of the blue”. She said that earlier investment and the application of SARS and MERS knowledge to Covid-19 were helpful. 

In 2020 Drs Peter Beyer and Sarah Paulin demanded “more public investment” to create a “viable economic environment” for responses to emerging health crises such as the priority list and AMR. They also expect pharmaceutical companies to get involved. However, this is a high-risk investment. How can policymakers encourage active involvement?  

Solving supply chain safety and sustainability concerns

Solving supply chain safety and sustainability concerns

Through healthcare crisis after healthcare crisis the need for safe and sustainable supply chains is more pressing than ever. Increasing need for cold-chain products requires innovative solutions and recent regulatory changes emphasise this requirement, hence Johnson and Johnson’s vaccine security seals. Smart labels react to heat and time, and black-light verification prevents counterfeiting. The US Drug Supply Chain Security Act will be implemented in November 2023 with the aim of creating a traceable supply chain. This reduces opportunities for counterfeit and fake medication. However, keeping up with these changes as well as meeting new expectations will be difficult. 

Leila Hawkins, in August 2022, stated that the “pharma business must also prioritise sustainability”. This will lead to more efficient operations, but what does sustainability look like in practice? Hawkins cites examples such as pre-qualified thermal packaging that “prolongs a product’s life”. This brings commercial benefits as a result of “temperature-controlled distribution process efficiency and simplified designs”.  

Hawkins suggests that the pharmaceutical industry is responsible for “50% more greenhouse emissions than the automotive industry.” Issues such as packaging going to landfill are a thorn in the side of the industry’s attempts to lighten its footprint. She explores how over-predicting packaging needs can cause an environmental headache. She promotes technology to help with “assessments regarding shipping conditions and packaging needs”. 

In a 2021 survey of third-party logistics on the cold chain by NTT Data, 31% of participants believed “proper packaging” to be their biggest challenge. As always, a collaborative approach will be critical in enacting lasting change. Hawkins suggests that choosing the right packaging partners allows stakeholders to enable improvements. She refers to the collaboration that allows Pfizer’s Covid-19 vaccine to spend 30 days in dry ice boxes that are replenished every 5 days. 

As we move from one pandemic to the next crisis, the industry faces an opportunity to develop more sustainable and efficient packaging practices.

If you would like to participate in supply chain discussions at the World Vaccine Congress in Europe 2022 click here to secure tickets! 

Demanding sustainable subscriptions for AMR

Demanding sustainable subscriptions for AMR

Drs Till Boularte and Ulrik Schilze of BCG stated in February 2022 that “when market forces fail to motivate adequate innovation, other incentives are necessary”. In our article on AMR we explored the risks involved in a highly volatile and expensive market. Shelley McLendon suggested that AMR would rage ahead without waiting for investors to respond to the challenges it raises.  

The pharmaceutical industry has been pushing incentives with “limited initial success” without changing the “underlying economics” of AMR. Thus, the authors demand a “new incentive model” to “support continuous innovation of truly novel antibiotics”. They identify investor willingness to accept high risks for the potential high reward. How can we capitalise on this in a sustainable way?

They suggest that “clear targets and reliable instruments” are critical, as well as an “aligned vision”. These terms are great in theory, but what do “aligned vision” and “clear targets” look like in practice? 

Addressing the private sector, which Boularte and Schulze believe to be capable of achieving the “volume and variety of innovation”, they identify a need for a “sustainable ecosystem” with both “push and pull incentives” to reward successful ventures. Additionally, a “set of agreed-on high-impact target pathogens” should unite public and private efforts. 

There are 6 success factors that they require: 

  1. A more viable ecosystem that aligns the interests of all participants, fostering investment and attracting talent to crucial R&D efforts.  
  2. Continuous innovation of novel antibiotics to counter the continuous decay of the existing antibiotic reserve and stay ahead of AMR.  
  3. Portfolio diversity with global relevance, targeting globally relevant pathogens and product profiles with a range of approaches and mechanisms of action 
  4. Supply surety and availability of novel products: sufficient infrastructure, ensuring product availability as needed and regional and local decentralised production 
  5. Appropriate stewardship through reliable diagnostics and surveillance, global antibiotic use guidelines, and active support for diagnostic solutions, including rapid point-of-care diagnostics for LMICs 
  6. Global access to novel antibiotics, including easy and inexpensive registration in markets with unmet needs, equitable global access, and public-private partnerships for LMICs 

They analyse a series of incentives in their article. Their conclusion was that the “subscription model” of fixed payments in return for sufficient antimicrobial product supply guarantee, delinked from volumes sold, would be imperfect but invigorating. They call on G7 countries, the EU, and China, to unite with the following goals: 

  • Collective understanding that the parties agree with the principle: paying for access as opposed to volume. 
  • Consider the advantages of a subscription model: it increases product availability and is ideal for stakeholders. 
  • Define and align a position regarding the size of the overall pull incentives. 
  • Collaborate with the WHO to establish a mechanism to prioritise TPPS. Form a “joint international scientific committee”. 
  • Get this committee to create a framework for an enhanced Health Technology Assessment to determine the value of a novel antibiotic.  
  • Achieve multilateral agreement on a fair-share methodology that identifies the resources each country contributes. 
  • Acknowledge that mechanisms will differ by country and work in parallel to identify feasible mechanisms.  
  • Urge G20 nations to determine how to handle access and stewardship of novel antibiotics to ensure the efficacy is protected.  
  • Set a clear time frame for implementation and align on the process with contributing countries.  

Their final words resound like McLendon’s warning – AMR will not wait for a unified international approach. So, how will this look in practice, and how much progress has been made 6 months after their call for action?  

For a day of AMR discussion at the World Vaccine Congress in Europe in October follow the link for tickets.

Operation Warp Speed is a wrap: farewell to funding

Operation Warp Speed is a wrap: farewell to funding

In typical American fashion the US Covid-19 vaccination development programme took the name “Operation Warp Speed” (OWS). OWS invested approximately $18 billion in clinical development and manufacturing of covid vaccines, with agreements to purchase 455 million doses. The Lancet describes it as “the largest of the global efforts”. This is compared to CEPI’s $1.4 billion to ensure global access.

Although the OWS was a financial powerhouse in the height of the pandemic, it was disbanded in 2021. Since then, the White House has continued to expect vaccine development, “no matter what Mother Nature throws at us”. At the vaccine summit in July 2022 the industry’s key players gathered to discuss future measures, aiming to meet Dr Ashish Jha’s ambition of “better than terrific”.  

However, noticeably absent from the White House’s enthusiasm was a congressional funding request or financial proposition. Dr Akiko Iwasaki of Yale University identified “lots of barriers” to progressing novel vaccination strategies, including her own nasal candidate. Quite apart from funding, a “shortage of nonhuman primates” presents a challenge.  

As it stands, CEPI has invested $200 million into 11 efforts and NIAID has contributed $43 million to 4 programmes. With this decreased funding, it’s no wonder that the “sense of urgency is completely gone” according to Dr Florian Krammer. Pushing forward with this research is what Dr Melanie Saville of CEPI classifies as “high-risk, high-reward”, but who is prepared to take the risk? As fresh variants and vaccine fatigue offer deterrents, we watch and wait to see who will dig deep. 

To participate in funding discussions with industry experts come to the World Vaccine Congress in 2022; get your tickets here.

Noses to the grindstone for nasal vaccines

Noses to the grindstone for nasal vaccines

Writing in Science in July 2022 Dr Eric Topol and Dr Akiko Iwasaki reflected on the “unprecedented success” of the mRNA vaccine programme in response to Covid-19. The next step, they suggested, is to translate the efficiency of the Covid-19 vaccines into nasal vaccine development. Meeting a “major unmet clinical need” shines a light onto the possibility of nasal vaccines.

The “allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots” appeals to Topol and Iwasaki, who draw our attention to what they describe as “substantial attrition” in the efficacy of current vaccines. With reference to specific variants and subsequent “variant-chasing” the “only path”, they say, will be nasal or oral vaccines.  

What are our options on the nasal vaccine scene? Topol and Iwasaki are ready with examples, 4 of which have progressed to Phase III trials: Bharat Biotech, Codagenix, Beijing Wantal Biological, and Razi Vaccine and Serum Research Institute. Despite these positive developments, they recognise that there are challenges to providing effective and safe nasal vaccines, which have been encountered in the past.

Currently FluMist is the only intranasal vaccine approved by the FDA, but it has a limited approval population. Furthermore, financial reticence leads to “substantial delays in manufacturing at scale, regulatory approval, and distribution.” They call for investment such as that in Operation Warp Speed (OWS) in the US to “get ahead of the virus and build on the initial success”. 

It remains to be seen whether there will be an appetite for this kind of development, particularly given the pace of the virus’ mutation and variation. 

Clinical tribulations – how can we grow from Covid-19?

Clinical tribulations – how can we grow from Covid-19?

Clinical trials are a critical stage in vaccine development, and during the Covid-19 pandemic we watched vaccines hurtle through the process at remarkable speed. However, vaccine development traditionally lasts a lot longer. So, what takes them so long?  

In the European Union the EMA, a decentralised agency of the European Union operating since 1995, sees approximately 4,000 clinical trials. Of this figure, 60% are sponsored by the pharmaceutical industry and 40% non-industry sponsors, such as academia.  

The EMA’s American sibling is the FDA, an agency within the Department of Health and Human Services. Even before a vaccine enters the clinical trial stages with the FDA an Investigational New Drug (IND) application must be submitted. In this application developers must present: 

  • Animal study data and toxicity 
  • Manufacturing information 
  • Clinical protocols 
  • Data from prior human research 
  • Information about the investigator 

Once this initial stage has been achieved, a drug can enter the Phase stage. The rigorous trial process follows a similar pattern on both sides of the pond. 

Clinical trials are an expensive process. Public health funding for clinical trials decreases every year, resulting in greater investment from the pharmaceutical industry. For example, in 2012 the NIH paid $31 billion for trials, whereas pharmaceutical companies contributed $8 billion more. Although reported to demonstrate systematic bias, trials that receive funding from the pharmaceutical industry are said to generate greater levels of evidence through higher numbers of patients. They are also published more easily in free-access journals, which increases the visibility of these trials.  

After the success and efficiency of the Covid-19 vaccine trials, a false sense of optimism might be felt among the public, perhaps previously ignorant of the process. Of the 70% that proceed from Phase 1 to 2 in the United States only 33% move to Phase 3. From there, only 25-30% are launched into Phase 4. As more diseases appear or reappear, will we be able to respond with such a collective and collaborative approach that tests the limits of scientific efficiency, and what did we do during the pandemic to get things done? 

VIE: looking back to last year’s winners!

VIE: looking back to last year’s winners!

The World Vaccine Congress in Washington DC, April 2022, was a resounding success with record numbers of attendees and speakers. For a lucky few it also presented the opportunity to have their contributions recognised in our prestigious 15th Vaccine Industry Excellence Awards! Read on to meet our 2022 ViE winners.  

Best Clinical Trial Site award – CTI Clinical Research Centre 

  • The CTI Clinical Research Centre is in Norwood, Ohio, and runs Phase I-IV studies for sponsors. They specialise in in “making sure our study participants are well-informed and comfortable”. 

Best Clinical Trial Network award – Alliance for Multispecialty Research 

  • The AMR aims to “conduct high quality, ethical clinical research” with a focus on patient welfare.  

Best Central/Speciality Laboratory award – Nexelis, a Q2 Solutions Company 

  • Nexelis describes itself as a “multinational powerhouse with unparalleled expertise in immunology” 

Best Contract Research Organisation award – Thermo Fisher Scientific’s PPD Clinical Research Services 

  • Thermo Fisher’s PPD services “enable customers to accelerate innovation and increase drug development productivity” by using “patient-centred strategies and data analytics”. 

Best Contract Manufacturing Organisation award – Catalent 

  • Catalent describes itself as the “global leader in enabling pharma, biotechnology, and consumer health partners”.  

Best Production/Process Development award – Batavia Biosciences 

  • Batavia Biosciences is a contract development and manufacturing organisation that aims to be a “product development partner and thought partner” instead of “your standard CDMO. 

Best New Vaccine Technology/Platform award – Moderna 

  • Moderna aims to “deliver on the promise of mRNA science to create a new generation of transformative medicines for patients”. 

Best Academic/Research Team award – Texas Children’s Hospital Centre for Vaccine Development – Dr Peter Hotez and Dr Maria Elena Botazzi 

  • The Centre for Vaccine Development has “led and revolutionised national and international efforts in threats to global health”. With “world leaders” driving their research, they are also involved in “science communications and public outreach”.  

Best Pharma award – Pfizer 

  • Pfizer describes itself as “in relentless pursuit of breakthroughs that change patients’ lives” to make the world a “healthier place”.  

Best Logistics Technology and Cold Chain Delivery award – DP World 

  • DP World is the “leading provider of smart logistics solutions” to promote the “flow of trade across the globe”.  

Best Covid Vaccine award – BioNTech/Pfizer 

  • BioNTech describes itself as a “global immunotherapy powerhouse” with the intention of translating “science into survival”.  

 

Who will get your vote for a shot (all puns intended) at glory at the 2023 World Vaccine Congress? To reserve your spot at the congress click here!

A helping hand from double, double toil and trouble

A helping hand from double, double toil and trouble

Audiuvare – to help.

Although the word “adjuvant” might suggest a group of earnest lab assistants, adjuvants are ingredients that provoke a stronger immune response to vaccines. These supplementary scientists encourage more local and systemic reactions to the vaccine and have done so for almost a century. They first appeared as contaminants in aluminium vessels, and are now a deliberate part of vaccine production.

An interview between Kristen Kresge Abboud and Dr Bali Pulendran for IAVI report explored the role of adjuvants in mRNA vaccines. They reflected that adjuvants are “one way to augment the durability of vaccine-induced immunity”. Dr Pulendran refers to adjuvants as a “sort of witches’ brew”. Spooky. His lab focuses on demystifying adjuvants with knowledge of innate immunity and the pathways they stimulate. The end goal of these investigations will be “rational” adjuvant design that captures the “magic of these witches’ brews”

Using the Covid-19 mRNA vaccines as a case study, Dr Pulendran discusses their efficacy considering “durability is related to signalling in the innate immune system”. Acknowledging that the vaccines are “truly transformative”, he suggests that the antibody response is short-lived, hence the booster requirements in the face of new variants.

He recalls that studies demonstrated that the yellow fever vaccine engaged multiple receptors within the innate immune system, and that this “synergistic engagement” was essential to antibody responses. Consequently, the next step was the development of a synthetic vaccine or virus that captured the “essential features” of this vaccine to stimulate “durable immunity”.

More recently, they did the same thing to the Pfizer/BioNTech mRNA vaccine and found that the T-cell responses were “more durable than the antibody responses”. The question, then, was can we “adjuvant the mRNA vaccine so it doesn’t suppress protein production, but it still provides the innate signalling required to get durable responses”? Currently several adjuvants are being explored, without clarity on which will be the best, but a recent subunit vaccine, adjuvanted with AS03, was approved after studies assessing a range in non-human primates.  

For a whole day of adjuvant discussion come to the pre-congress adjuvant workshop at the World Vaccine Congress in Barcelona October 2022: book your tickets here

Vaccines: more than just a “sharp scratch”?

Vaccines: more than just a “sharp scratch”?

When most of us think of vaccines we have visions of a nurse with a sharp needle, approaching a bared forearm. Although this is the most conventional means of administration, there is a variety to choose from, with different effects and efficacies. In this article we explore some of the methods of delivering vaccines.  

Injected  

  • Intramuscular: many vaccines are injected into muscle tissue – such as the upper arm or thigh. Muscles contain many blood vessels so that the vaccine is quickly distributed into circulation. The benefits include limited side effects although thy should be administered by trained healthcare professionals to reduce damage to nerves or blood vessels.  
  • Subcutaneous: a few vaccines are injected into a layer of fat beneath the skin, which has fewer blood vessels than the muscle. This results in a slower, more constant release, ideal for the delivery of some live attenuated vaccines and inactivated vaccines. These are ideal for self-administration often in the abdomen or thigh.  
  • Intradermal: currently mostly used for allergy testing but also for the administration of rabies and tuberculosis (BCG) vaccines. This method is useful because the skin contains many immune cells and could therefore be more efficient – less of the vaccine might be needed, meaning more doses for more people! However, the skin is so thin that these injections are generally administered by trained health professionals. 
  • Intravenous: occasionally medicines are delivered directly into the veins, a speedy and effective method of distribution. Vaccines haven’t generally been administered this way, but initial evidence suggests that the tuberculosis and malaria vaccines might be more effective. Once again, hitting the right spot is a tricky task, so we rely on trained healthcare professionals to do this!  
  • Injections often cause pain and concern among patients, which leads to vaccine fear or hesitancy. Another issue is the risk of injury or contamination through reuse, as well as short supply. 

Oral  

  • Oral vaccines are swallowed, great for people who are afraid of injections. A 2021 poll by Vaxart revealed that nearly 19 million Americans who did not want an injectable vaccine would receive the oral dose.  
  • Easier to manufacture and administer, they can be delivered by people without specific training, so they have greater distribution potential.  
  • Oral vaccines are encountered by immune cells in the mucosa as well as those in the bodily fluids. They are therefore effective in protecting against gut infections like cholera and polio as pathogens must cross the mucosa to infect the gut.  
  • Unfortunately, only a few vaccines are licensed for oral administration, including the polio vaccine. This is because the vaccine passes through the gastrointestinal conditions and must be able to avoid the mucosal tolerance – this stops our immune systems from responding to antigens that we consume in food.   

Mucosal 

  • Mucosal sites include oral, nasal, ocular, rectal, and vaginal.  
  • These are particularly effective in epidemics of infections that are transmitted mucosally.  
  • The cost of producing and delivering these vaccines is lower and purity is not as critical as it is for injected vaccines.  

Patch 

  • The Vaccine-containing Mircoarray Patch (VMAP) is an intradermal technique. UNICEF is currently pushing for further research and development of these vaccines because they increase accessibility and ease administration. 
  • They arrive ready to administer and will likely be more stable at a wider range of temperatures. They can be delivered by health workers with very little training, meaning greater uptake in areas that previously presented vaccine challenges. 
  • PATH suggests that “true vaccine equity” can be achieved through investment into a range of formulation technologies, of which the patch might be one. 
  • The need for needles is eliminated, waste is reduced, and storage and transport become easier. However, there is a need to ensure market incentives by vaccine manufacturers as the cost is likely to be higher until offset through delivery.  

 

Book your World Vaccine Congress tickets to Barcelona in October 2022 to hear Dr Sean Tucker of Vaxart discussing oral vaccine administration here