News shared by the University of Queensland (UQ) in December 2023 explains how a paper in Molecular Therapy Nucleic Acids presents positive results from a study investigating the stability, efficacy, and immunogenicity of a DNA vaccine delivered to the skin through HD-MAP technology. The vaccine was developed to protect people from the “potentially deadly mosquito borne Zika virus”. This technology, developed by UQ and commercialised by Vaxxas, has previously been financially recognised by CEPI and Wellcome.
Zika
The researchers describe Zika virus (ZIKV) as a “re-emerging flavivirus” that is most frequently transmitted by blood meals of a mosquito. However, sexual and vertical transmission have been “well-documented”. First identified as a cause of human infections in the 1950s, it has caused “sporadic outbreaks”; an example of this was the 2015-2016 outbreak, during which “millions” of people in the Americas were believed or confirmed to be infected.
Despite a decline in global incidence of ZIKV researchers emphasise how “important” it is to “continue ZIKV vaccine development” for emergency use in the “likely event” of a future outbreak. The ZIKV genome encodes three structural proteins that are important for cell entry including premembrane (prM) and envelope (E); most vaccine development efforts have focused on targeting prM and E. Unfortunately, antibodies against the virion surface E protein reportedly have the potential to enhance infection of dengue virus, and vice versa, in countries where the viruses co-circulate.
DNA vaccines
“DNA vaccines are inexpensive, easy to construct, stable at room temperature, and have minimum side effects, which simplifies handling and distribution, suggesting the potential for equitable global distribution of this type of vaccine.”
The study suggests that DNA vaccines that elicited protective neutralising antibodies to ZIKV in mice and rhesus macaques were developed. The team developed a proprietary DNA vaccine (pVAX-tpaNS1) that encodes codon-optimised NS1 protein from the Brazilian strain of ZIKV with a tissue plasminogen activator signal sequence to facilitate effective NS1 secretion. However, the “potential” of the DNA vaccines is “still not fully realised” because of “poor delivery and antigen expression” as well as the “lack of a localised inflammatory response”.
DNA vaccines derive “significant” benefits from delivery into the dermal layers of the skin. Therefore, the high-density microarray patch (HD-MAP) vaccine delivery technology is once again tested, in this case to see if pVAX-tpaNS1 could elicit more potent NS1-specific immunity in vivo and protection against ZIKV in comparison with ‘traditional’ needle and syringe vaccination.
A better method
Dr Danushka Wijesundara, UQ alum and Vaxxas researcher, commented that the virus presents a risk to many people across the globe, but the latest research shows a potential improvement to disease control.
“We can change the way we combat Zika virus with the HD-MAP patch because it is an effective, pain-free, simple to apply, and easy to store vaccination method.”
Dr Wijesundara suggests that in the trial “the vaccine provided rapid protection against live Zika virus”.
“The vaccine patch evoked T-cell responses that were about 270% higher than from a needle or syringe vaccine delivery.”
The University of Adelaide’s Associate Professor Branka Grubor-Bauk states that, while there is no licensed vaccine, the virus is known to be active in at least 89 countries and territories.
“This vaccine is unique because it targets a protein inside, rather than outside of the virus meaning it won’t enhance the symptoms of closely related viruses.”
Dr David Muller of UQ hopes that the team’s research will have applications beyond a potential Zika vaccine.
“Because the protein we’re targeting plays a central role in replication in a virus family known as flaviviruses, there’s the potential to apply our approach to target other flaviviruses such as dengue or Japanese encephalitis.”
Furthermore, the technology could deliver a vaccine “mixture” to target the “whole family” and provide “greater protection”. Finally, Dr Muller reflects that a “major benefit” of the HD-MAP platform is the “vaccine stability at elevated temperatures”.
“We found the patch retained vaccine potency when stored at 40 degrees Celsius for up to four weeks…This increases the reach of vaccines in low- and middle-income countries where refrigeration is challenging.”
We look forward to hearing more from Vaxxas on their unique delivery approach at the Congress in Washington next year. You can join us by getting your tickets here or subscribe for more updates on vaccine technology.
In research shared by the University of Bristol in November 2023, a team demonstrates the validity of nature-inspired nanoparticle-based reagents using an approach that combined “synthetic, computational, and structural methods” with “in vitro antibdody selection and in vivo immunisation”. The paper, in Antibody Therapeutics, suggests that Imophoron’s Adenovirus-derived dodecamer (ADDomer)-based nanoparticles can be effectively used in active and passive immunisation. Furthermore, the team states that this research “provides a blueprint for crafting reagents to combat respiratory viral infections”.
ADDomer technology
The researchers recall that “shortly before” the start of the COVID-19 pandemic, they introduce Adenovirus-derived dodecamer (ADDomer); this is a “synthetic self-assembling protein nanoparticle platform for highly efficient vaccination by genetically encoded multiepitope display”. It “derives from a single protein component” of adenovirus, which “forms pentons at the vertices of the viral capsid” to provide a “base for the attachment of the adenoviral fibre”.
“When produced recombinantly in isolation, 60 copies of this penton-base protomer spontaneously self-assemble in the test-tube into a dodecahedron comprising 12 pentons.”
ADDomer can be stable over 50°C and stored at ambient temperature for prolonged periods; this suggests that ADDomer-based vaccines and therapeutics could be “potentially produced, stored, and transported” without requiring refrigeration.
Study goals
The study aim was to develop a thermostable ADDomer-based COVID-19 vaccine that could overcome “limitations associated with the cold-chain challenge” but maintain the advantages offered by the technology. The vaccine, ADDoCoV, was validated by near-atomic resolution electron cryo-microscopy (cryo-EM) and molecular dynamics (MD) in a “hybrid approach”.
To confirm “authenticity and accessibility of the displayed immunogenic epitopes” the team deployed Ribosome Display. Furthermore, the “prowess” of the ADDoCoV design was demonstrated by the immunisation of mice to elicit antigen-specific IgA and IgG antibody responses and the induction of mucosal immune responses.
Pandemic preparedness
Professor Imre Berge of the University of Bristol reflected that the COVID-19 pandemic “reminds us of the critical importance of being prepared” as well as the need for “innovative approaches” to accelerate and ameliorate vaccine development.
“Our study demonstrates the use of ADDomer-based nanoparticles in active and passive immunisation and provides a blueprint for developing reagents and vaccines to tackle respiratory infections.”
Chief Executive of Imophoron, Richard Bungay, commented that the “important” paper highlights the “significant” potential of the company’s “unique’ platforms in developing “novel, thermostable vaccines to combat infectious diseases”.
“The research represents a significant milestone for our team of world-class scientists, in collaboration with the excellent team at the University of Bristol, in our ongoing commitment to advancing global health.”
In November 2023 Merck, which is known as MSD outside the US and Canada, announced results from a Phase III trial evaluating the company’s investigational 21-valent pneumococcal conjugate vaccine for protection of adults. The release was followed up by details shared at the World Vaccine Congress West Coast on the same day. The trial, STRIDE-3, evaluated the immunogenicity, tolerability, and safety of V116 in comparison with PCV20 in adults who had not previously received a pneumococcal vaccine.
V116
V116 is an investigational, 21-valent pneumococcal conjugate vaccine for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in the adult population. It is “specifically designed” to address Streptococcus pneumoniae serotypes that are predominantly responsible for adult pneumococcal disease, included eight that account for approximately 30% of adult disease. CDC data from 2018-2021 indicate that the serotypes covered by V116 are responsible for around 83% of invasive pneumococcal disease in adults aged 65 and older.
What does the study find?
Results from STRIDE-3 primary objectives include:
In adults aged 50 and above (Cohort 1), V116 elicited non-inferior immune responses compared to PCV20 for all 10 serotypes common to both vaccines as measured by serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMT) at Day 30.
Immune responses elicited by V116 were superior for 10 of 11 serotypes included in V116 but not in PCV20 as measured by OPA GMT at Day 30 and the proportions of patients with a greater than or equal to four-fold increase in OPA from Day 1 to Day 30.
In adults between the ages of 18 and 49 (Cohort 2), V116 elicited non-inferior immune responses (immunobridged) compared to adults between the ages of 50 and 64, as assessed by serotype specific OPA GMTs 30 days after vaccination.
Across both cohorts, V116 had a safety profile comparable to PCV20.
The Phase III clinical development programme comprises eight trials in various adult populations, including adults with and without chronic medical conditions associated with increased risk of pneumococcal disease.
Exciting potential
Dr Eliav Barr, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, is “excited by the potential” the vaccine has, to shape public health.
“These results provide strong evidence to support the immunogenicity of V116 compared to the standard of care in the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults.”
Principal Investigator of the study, Dr Sady Alpizar of Clinical Research Trials of Florida, Inc., commented that “invasive forms” of the disease can cause “serious and sometimes life-threatening complications”.
“These encouraging results demonstrate the V116 has the potential to help prevent invasive pneumococcal disease among vulnerable populations.”
We were glad to hear more from Dr Heather Platt and Dr Morgan Monslow yesterday in their sessions at the Congress in Santa Clara. If you weren’t able to join us do make sure you subscribe for more insights here.
In November 2023 the University of Saskatchewan’s Vaccine and Infectious Disease Organisation (VIDO) announced that it has been awarded an Indefinite Delivery/Indefinite Quantity (IDIQ) contract by the US NIAID. One of seven organisations selected to be a member in the NIAID service provider pool, VIDO is the only non-US organisation and the only University-based organisation to be included.
7-year IDIQ for VIDO
An IDIQ means that the quantity of products or services that will be delivered has not yet been delivered. This creates more flexibility for the government. The contract awarded to VIDO will last seven years and is valued up to US$30 million.
“VIDO’s Vaccine Development Centre will play an important role in providing services that will help a wide variety of researchers obtain the critical data needed to advance products, partnerships, and complete studies needed to enter clinical trials.”
VIDO describes itself as a “world leader” in infectious disease research and vaccine development for humans and animals.
“VIDO’s expertise, infrastructure, and history put us at the forefront of innovation and make us a valuable resource and a source of pride for Canada.”
It has over 45 years of experience in “developing solutions” to emerging threats, which informed its “key role” in Canada’s COVID-19 response.
A vote of confidence
Honourable Dan Vandal, Minister for PrairiesCan, described the news as a “vote of confidence” in VIDO’s capabilities and an “international recognition of their status as a world-class hub”.
“This contract marks an important step in Canada’s Biomanufacturing and Life Sciences Strategy – generating economic growth, a strong biomanufacturing ecosystem, and ensuring Canada can lead the response to global infections disease emergencies.”
Minister of Innovation, Science, and Industry, Honourable Francois-Philippe Champagne, is “proud” to invest in VIDO to “better protect the health and safety of Canadians” by providing access to vaccines.
“VIDO’s crucial work is putting a spotlight on Canadian scientists while contributing to our efforts to rebuild a strong domestic biomanufacturing and life sciences sector.”
Jeremy Harrison, Minister Responsible for Innovation Saskatchewan, Government of Saskatchewan, described VIDO as “at the forefront of vaccine research and development in Canada”.
“This opportunity will provide critical product advancement and new prospects for economic growth in our province.”
President of the University of Saskatchewan, Peter Stoicheff, commented that the scientists at VIDO are contributing to pandemic preparation with vaccine and treatment development.
“This contract with the NIAID reinforces our commitment to being the university the world needs.”
Dr Volker Gerdts, VIDO’s Director and CEO, is glad of the opportunity to “engage agencies like the NIAID” as part of the “international engagement strategy”.
“Infectious diseases are a global issue and VIDO is making an increasingly broad and global impact on vaccine development.”
For more on recent partnerships and vaccine development, don’t forget to subscribe here.
With the World Vaccine Congress West Coast kicking off we are pleased to share another exclusive interview. This time we are glad that start-up VacTrack were happy to catch up with us again after our interview in Washington earlier this year. We spoke to Gabriella Hakim and Emily Gaizley about their progress and goals for the Congress. This was a written interview, conducted over email. We hope you enjoy it!
Introducing Gabriella and Emily
After meeting Gabriella at the Congress in Washington we were glad that she and Emily were keen to reconnect, so let’s kick off with a reminder of who they are and what they do!
“Gabriella came up with the idea for VacTrack from her own personal annoyance with the current paper-based system used to monitor vaccinations.”
With a medicine background, Gabriella is “acutely aware of the needs of both patients and clinicians”. As CEO, she has developed the team and vision, becoming the “driving force” behind VacTrack’s brand and network.
Emily brings a scientific background to her work, with experience in pre-clinical cancer research, which she combines with financial services experience for a “data-driven approach to solving problems”. As Chief Scientific Officer, Emily has “developed and shaped” VacTrack’s products and commercial strategy.
Changing with the times
We reflect that in our last conversation, Gabriella described the approach she and her team are taking as a “digital solution”; we asked about whether the scope of the organisation has changed as the global approach to the pandemic has changed.
“During the pandemic, VacTrack’s patient-centric app was critical for empowering individuals to take control of their own immunity. However, it is becoming increasingly clear that a coherent and sustainable digital global strategy is required to reverse the trend of decreasing population immunity.”
How do Gabriella and Emily think this will be achieved? They suggest that “improved crosstalk” between private and public sector vaccine providers will drive the change. Therefore, VacTrack is developing “digital solutions to unburden clinicians from administrative efforts”. This will enable “streamlined” vaccine programme management with “automated appointment scheduling and personalised guidance”.
“We hope our products will lead the digital transition of vaccine-preventable disease management.”
Public confidence
Our next question focuses on public attitudes, which are susceptible to change and impressionable. We asked how VacTrack empowers patients to feel confident in immunisation. Gabriella and Emily believe that “creating a direct link” between “developers, providers, and patients”, facilitates “transparent and cohesive communication between stakeholders”. A particular target with this strategy is the “disparate and non-cohesive advice” that allows misinformation to spread.
“VacTrack allows patients report side-effects and concerns, which can be curated, analysed, and fed back into the vaccine-development ecosystem with the aim of improving the experience for patients.”
Contacts in the community
A key message from Gabriella’s previous interview was the importance of working on your contacts within the community. She and Emily state that they have been “fortunate” to maintain some of those that were made at the Washington Congress, which is great to hear!
“These relationships are vital for the growth of the company, and we have made every effort to work with our potential partners closely and efficiently.”
Overcoming challenges
This leads into our next question about managing the trials and tribulations of start-up development! Gabriella and Emily recognise that a “global solution requires communication with lots of stakeholders” and that this can be “challenging to manage”.
“As a mission-oriented company we never lose sight of our overarching aim, which is to improve disease prevention.”
Keeping the goal in mind enables the team to “stay focused and manage partnerships effectively”. Gabriella and Emily also suggest that “with over 260 vaccines in development” for therapeutic or prophylactic purposes, it is a “daunting task to stay ahead of the curve”. However, their resolve is evident as they assure is that this also provides an “exciting opportunity to make a tangible difference” with a “technology-based solution that is easy to access”.
“As the production of vaccines increases, we want to ensure that we are available to see patients through their immunity, whilst also ensuring patients adhere to those already available in the market. Tracking vaccine adherence is at the root of what we are trying to achieve, and we hope this solution enables patients to stay on track with their vaccination schedules.”
The West Coast Congress
After attending the Washington event, we are keen to hear what VacTrack’s ambitions for the West Coast Congress are. Gabriella and Emily reflect that the Washington Congress was a “fantastic experience” and being “among the vaccine leaders of the world” was a “great privilege”. They emphasise the benefits of learning from “incredible insights” in a range of vaccine areas.
“We look forward to strengthening already established connections we have made and to making news ones to see VacTrack through its progress and expansion.”
We hope the West Coast Congress proves as successful as the Washington event for VacTrack, and encourage attendees to seek them out for a conversation! Thank you for reading, and if you are headed to Santa Clara have a safe journey and a fantastic event! If you can’t make it, make sure you subscribe for more interviews from our Congress community.
The University of Queensland (UQ) announced in November 2023 that its “re-engineered clamp platform” has produced a vaccine that is “equally safe and virus-neutralising” as an approved vaccine “considered among the best in its class”. This technology was identified by CEPI as worthy of investment, committing up to AU$8.5 million last year to support development for use in disease prevention.
An exciting reward
The results of a preliminary clinical trial are described by the project leader, Associate Professor Keith Chappell, as an exciting reward for the team’s dedication to the project.
“We compared second-generation clamp SARS-CoV-2 vaccine head-to-head with TGA-approved Nuvaxovid, and the two were found to be functionally equivalent.”
Furthermore, while the two vaccines produced “highly comparable results”, there were no new COVID-19 infections among the Clamp2 volunteers, while 3 cases were detected among Nuvaxovid recipients to date.
CEPI’s approval
As we noted almost exactly a year ago, CEPI recognised the technology as a promising investment, and has therefore reacted positively to the UQ update. Dr In-Kyu, Director Programmes and Innovative Technology at CEPI, believes that advancing vaccine platforms like this clamp technology is crucial for preparing to respond to emerging infectious threats.
“CEPI is striving towards vaccines being developed within 100 days of a new virus emerging: a goal known as the 100 Days Mission. I look forward to the continued progress of this cutting-edge technology.”
UQ emphasises that the partnering agreement and CEPI’s equitable access policy will be followed to ensure that vaccine candidates produced using this platform technology will be available in an outbreak situation to “populations at risk including in low-income and middle-income countries”.
The next stage of health for Queensland
The technology will now progress to the next phase with UQ’s commercialisation company UniQuest licensing the technology to Vicebio, which is “progressing its use against respiratory pathogens”, said Associate Professor Chappell. UQ states that this progress has been supported by the Queensland and Australian Governments and partners. Queensland Deputy Premier, Steven Miles, is proud of Queensland’s leading role in vaccine research.
“Advances in medical technology play a key role in bettering the health of Queenslanders throughout the state, and the Palaszczuk Government is committed to backing manufacturing here – made in Queensland by Queenslanders.”
In November 2023 SK bioscience and Hilleman Laboratories shared that they have entered into a development licensing agreement for joint development of a second-generation Zaire Ebola virus vaccine. The stated goal is “increasing production process productivity” and “improving product thermostability” to increase global Ebola vaccine supply and “expand access”.
What is Zaire?
WHO states that Ebola virus disease (EVD) is a “rare but severe” illness in humans that is “often fatal”. Ebolavirus is one of three genera within the Filoviridae family, and comprises 6 identified species: Zaire, Bundibugyo, Sudan, Taï Forest, Reston, and Bombali. The natural Ebola virus hosts are believed to be fruit bats of the Pteropodidae family, and the virus is introduced into the human population through close contact with bodily fluids with infected animals.
The Zaire strain takes its name from the first recorded outbreaks of fatal haemorrhagic fever in the Democratic Republic of Congo (formerly Zaire) near the Ebola River. Although there is an effective vaccine for the Zaire type, it has been the leading cause of outbreaks in the last 20 years.
What does the agreement offer?
SK bioscience states that it will acquire “unique expertise and know-how” for use of the rVSV (recombinant Vesicular Stomatitis Virus Vector) technology platform. The organisation will work closely with Hilleman Laboratories to “potentially jointly develop other vaccines” for viral indications.
Dr Raman Rao, CEO of Hilleman Laboratories, commented that “core” to the Hilleman Laboratories “mission” is “developing vaccines that are more affordable and accessible”.
“Our collaboration with SK biosciences on such an impactful vaccine programme will allow us to create positive outcomes for global public health, especially in affected regions of Central and Western Africa.”
Jaeyong Ahn, SK bioscience CEO, agreed that the pursuit of a vaccine against “diseases with a high fatality rate” such as Ebola, is an “essential task for us to protect humanity”.
“By cooperating with Hilleman Laboratories for a successful development of the second-generation Zaire Ebolavirus vaccine we will contribute to overcome the Ebola Zaire disease burden and expand our cooperation with global companies and institutions.”
Our next Congress Conversation from the event in Barcelona last month is with Andreas Regnery, who represented Belyntic in our start-up zone. It’s great to hear from our start-up community about the innovation that they are bringing to the scene, and to learn how the Congress gives them a platform for making change. If you are interested in joining us as a start-up at a future event, please get in touch with Isabella Aung (isabella.aung@terrapinn.com) for more information. We hope you enjoy the interview!
Introducing Andreas
Andreas kindly introduces himself as “co-founder and managing director” of Belyntic (you can also find them on LinkedIn). He and his colleague, Oliver, combine different experience, with Andreas bringing a more business-focused approach to the organisation. Belyntic is “the precision vaccines company”, stating that it targets viral infections with “novel precision vaccines”.
Unmet disease needs
Belyntic’s website describes how the team targets diseases with a “clear unmet medical need”. So, what kind of diseases are these? Andreas suggests that they are “particularly targeting viral diseases, especially those that have a high seroprevalence”. He refers to the first asset that they want to develop: a prophylactic CMV vaccine. Cytomegalovirus (CMV) is “usually harmless” but can be problematic for young infants and people with weakened immune systems. Andreas states that, depending on the sub-population, the seroprevalence can be up to 97%.
“These are very abundant viruses around the world, and they can break out, especially in immunosuppressed people…these diseases can cause really a lot of pain.”
Talking technology
The diseases in question pose an “unmet” need, so how does Andreas’ team hope to tackle them? Belyntic stresses “an emphasis on safe induction of cellular immunity”, so we asked about how this is achieved.
“Compared to other approaches, we’re really particularly focusing on T cell immune response, which does not mean that we solely induce T cell responses, but we have so-called self-adjuvant vaccines.”
These vaccines include MHC I and MHC II epitopes. Andreas explains that a “particular strength” of the technology is that they “only induce the minimum sequence of an antigen that is proven to be very immunogenic”.
“Therefore we have a very targeted immune response.”
With a focus on reactivation of viruses, the team ensures that the target population, for example immunosuppressed patients, is immunologically prepared to “defend” against disease.
“We’re convinced we have a solution”
When we speak to our start-ups we often ask about the difficulties or opportunities they identify in ‘breaking in’ to the vaccine space; how receptive is the community?
“Yeah, I think we are here because we are convinced that we have a solution for a really unmet area.”
However, Andreas recognises that due to the “tremendous success of mRNA vaccines” in the COVID-19 pandemic some people take an mRNA-or-nothing approach!
“But of course there are other technologies around as well, that in my opinion all have their advantages…and so do we.”
Andreas reflects that it takes “extra convincing” to convey the importance of non-mRNA vaccines, especially with peptide-based vaccines; they have had a “rather mixed history”.
“But it’s also lessons learned, I mean what we do is completely new, and we’ve overcome a lot of the past disadvantages.”
Could this technology be as revolutionary as mRNA was during COVID-19? Andreas certainly hopes so!
What does the future hold?
Andreas mentions future pandemics or viral threats, and we asked what the future holds for him and his team. He states that the focus is on “unmet medical needs” in viral diseases: “this is what we want to tackle”.
“Even though we just had the pandemic, and everyone around the world knows what this can cause patients…it’s still true that a lot of viruses are completely unmet.”
He calls for “much more work” on these areas.
“We hope that we as a company can help to tackle these problems, and that’s why we’re around!”
Why WVC?
Our final question, as always, uncovers our interviewee’s reasons for attending the Congress!
“I’m looking forward to meeting other innovative people…here you don’t need to convince others that vaccines are really important.”
He also was looking forward to seeing other innovations and connecting with people with “similar backgrounds and similar interests”, so we hope this was a productive time for it!
We were thrilled to speak to Andreas about his work and his time at our event, and hope you enjoyed learning more about his team’s work. For more, visit the website and don’t forget to get in touch if you would like to join Belyntic in the start-up zone in the future! For more insights and interviews, don’t forget to subscribe here.
In November 2023 Micron Biomedical announced that the Bill and Melinda Gates Foundation has committed a $23.6 million grant to fund “mass production” of needle-free vaccines. A manufacturing facility will enable commercialisation of a microarray technology-based measles-rubella vaccine, indicated for children “as young as 9 months” after approval from appropriate regulatory authorities. This approval will be informed by earlier successful clinical data and additional clinical study.
Encouraging equitable access
Micron Biomedical states that measles remains a leading cause of death in low- and middle-income countries “primarily due to limited access to vaccines that require refrigeration during transport and storage and clinicians to administer them”. Micron’s technology reduces this requirement and will allow a community health worker to administer the vaccine “within minutes” through application and a button to confirm administration. Furthermore, this process is “virtually pain-free”.
James Goodson, Senior Scientist and Epidemiologist in the Global Immunisation Division at CDC, commented that these vaccines could provide an “alternative approach” to “life-saving vaccines” for children in regions with “some of the highest rates of unimmunised children in the world”. The technology could “help overcome some of the most substantial barriers” to measles and rubella eradication.
“Vaccines are among the most effective and cost-effective tools to prevent measles and rubella, diseases that account for an estimated 350 deaths per day with a disproportionate impact on people living in low- and middle-income countries.”
Steven Damon, CEO of Micron Biomedical, is “grateful” to the Gates Foundation for a grant that will allow the team to “build on our collaborative track record” of “bringing effective and life-saving vaccines” to communities with “limited infrastructure”.
“By supporting Micron’s efforts to develop a state-of-the-art, high-quality, and large-scale production facility to manufacture our microarray technology, we have an opportunity to greatly improve on access and availability of measles/rubella vaccines, as well as other traditionally injectable global health vaccines, in underserved populations.”
Mr Damon suggests that the production facility “establishes Micron’s proof of concept” for “additional commercial vaccines and drugs in all markets globally”.
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Next up in our exciting Congress Conversations series is an interview with Genoskin’s Dr Nicolas Gaudenzio. He joined us at the Congress for a technology showcase, presenting on optimising vaccine candidate selection with an “insight into VaxSkin’s human skin-based multimodal immune profiling system”. We are glad that he was able to make some time to share some information on the work his team is doing to revolutionise vaccine discovery and development, and we hope that you enjoy the interview!
Introducing Dr Gaudenzio
Dr Gaudenzio explains that he is the Chief Scientific Officer at Genoskin and Principal Investigator at Inserm. Genoskin is a French-American biotech company based in Toulouse and Salem.
“We have built a network of surgeons in hospital in Europe and in the US and we actually obtain donated human skin samples that we preserve alive, in a culture dish, and that we use actually to test the safety and efficacy of different drugs that would be administered through the subcutaneous route.”
What happens at the site of injection?
We asked Dr Gaudenzio to give us an insight into what actually happens at the site of injection and how this informs the work that Genoskin is doing. He explains that how we currently “assess” and “study” the effects of vaccination in people is through a blood draw, days or weeks after an injection, to examine the presence of antibodies or antigen-specific immune cells.
“But what’s going on actually at the site of injection, when we inject the vaccine, it’s still a black box.”
Genoskin, therefore, tests vaccines in donated skin samples. The team injects vaccine candidates into “samples from multiple donors” to “reproduce the heterogeneity of the population”. This allows them to understand two things: “what’s going on at the tissue level and then what’s going on at the single cell level”. At tissue level, they can understand the risks of the vaccine and how it will “modify the skin ecosystem”. At single cell level they can understand the type of immune cells that uptake the vaccine, how it’s received, and how this uptake will activate specific cells.
“And so we mix different technologies; we mix some transcriptomic analyses, proteomic analyses, and we integrate all those data with some AI and machine learning systems to better understand and get really actionable insights.”
If this technology is new to you, questions about the benefit might arise. We asked how this approach is different, and better, than other, more ‘traditional’ approaches. Dr Gaudenzio suggests that the data are “100% human”. Therefore, they do not “extrapolate data from animal studies”. This has several benefits, not only for the animals; the team gets the “true reaction” that would happen in the human organ.
“This is a very valuable information because there is always a gap between when we finish the animal studies and then we go into the clinic, what’s going to happen in the patients?”
The “opportunity” that is offered by Genoskin’s technology is a “fully immunocompetent organ” that provides “a lot of information” so we can predict what will happen in the patient.
How receptive is the community?
When we consider these innovative technologies, a question that often springs to mind is about the reception they might get from the established vaccine community. We asked Dr Gaudenzio about entering the space and offering new solutions; how easy or hard is it? He suggests that this community is “experiencing the same problem”: “how do we translate animal studies into prediction for humans”? Different approaches are being explored, but none offer the “solution that is needed”. Indeed, “people are also coming to us directly” to discuss collaboration.
“Something very unique, I think of our approach, is to be able to study our immune system, the human immune system, in its native environment…I think this is something very valuable, and it seems to be appreciated so far by the community!”
Why WVC?
Our final question, as always, gives our experts an opportunity to share what they are looking forward to at the event.
“I’m looking forward to exchange with many people!”
Not only that, Dr Gaudenzio, like other speakers, was looking forward to enjoying our beautiful Spanish setting.
We hope that the Congress was fruitful for Dr Gaudenzio, and that you enjoy learning more about his work! Thank you to Dr Gaudenzio for his time and insight. For more like this, don’t forget to subscribe here.
In November 2023 Valneva announced that the US FDA has approved its single-dose, live-attenuated vaccine for the prevention of disease caused by chikungunya virus: IXCHIQ. The vaccine has been approved for individuals aged 18 or above who are at “increased risk of exposure” to chikungunya (CHIKV). The approval was granted under accelerated approval based on anti-CHIKV neutralising antibody titers, and continued approval for the indication relies on confirmation of clinical benefit in confirmatory studies.
What is CHIKV?
Chikungunya is a mosquito-borne viral disease caused by chikungunya virus, a member of the Togaviridae family. It is transmitted by Aedes mosquitoes, endemic in parts of the Americas, parts of Africa, and Southeast Asia. Infection provokes symptomatic disease in up to 97% of humans after 4-7 days after a mosquito bite. These symptoms include acute onset of fever, debilitating pain, headaches, and nausea.
“While mortality with CHIKV is low, morbidity is high.”
The virus often causes “sudden” outbreaks with “high attack rates”, affecting between one-third and three-quarters of the population in areas where the virus is circulating. The economic effects are considered “significant”, and the medical and economic burden will grow as the primary mosquito vectors increase their geographic spread.
“The global market for vaccines against chikungunya is estimated to exceed $500 million annually by 2032.”
Until this approval there were no approved vaccines or effective treatments, allowing chikungunya to be a “major public health threat”.
IXCHIQ
In the US, IXCHIQ is a live-attenuated vaccine indicated for the prevention of disease caused by CHIKV in adults aged 18 and above who are “at increased risk of exposure”. It is administered as a single dose by intramuscular injection. Valneva reports that, with this approval, the vaccine becomes the “world’s first licensed chikungunya vaccine” to address the “unmet medical need”.
Pivotal Phase III results were shared in The Lancet in June 2023, but the company will continue to evaluate antibody persistence for “at least five years”. The FDA states that it is “requiring” Valneva to conduct a post marketing study to “assess the serious risk” of “serve chikungunya-like adverse reactions” following administration of the vaccine.
An ongoing clinical study in adolescents between the ages of 12 and 17 is continuing in Brazil. This forms part of an agreement between Instituto Butantan and Valneva in January 2021 to ensure the vaccine is “more accessible” to low- and middle-income countries (LMICs). This study is funded by CEPI and could support future regulatory submissions in the age group and licensure in Brazil, signifying the first potential approval for use in an endemic region.
Valneva also expects this study to support regulatory approval in Europe; initial safety data was included in a submission to the EMA last month. The vaccine was granted PRIME designation by EMA in 2020. A regulatory review is also taking place in Canada.
Who will benefit?
Valneva suggests that the vaccine will “initially” address the “potential needs” of US travellers, fitting “seamlessly into Valneva’s global established travel vaccines business”. The company intends to begin commercialising IXCHIQ in the US at the start of 2024, while “continuing to support the work towards an anticipated vote” from the Advisory Committee on Immunisation Practices at the end of February. FDA’s Director of the Centre for Biologics Evaluation and Research, Dr Peter Marks, is hoping that “older adults and individuals with underlying health conditions” will benefit.
“Today’s approval addresses an unmet medical need and is an important advancement in the prevention of a potentially debilitating disease with limited treatment options.”
The approval is a source of pride for Valneva’s CEO Thomas Lingelbach, whom we interviewed at the Congress in Washington this April about “unmet medical needs”. He described it as an “important step forward” and “personally” expressed “a huge thank you” to everyone involved. Notably, he looks forward to the ongoing trial results.
“I would also like to recognise CEPI and Instituto Butantan for their collaboration in potentially bringing this product to low- and middle-income countries.”
CEPI’s CEO Dr Richard Hatchett is “proud” of his organisation’s contribution and offered his congratulations to “our partner Valneva” on “this historic achievement”.
“The first-ever licensed chikungunya vaccine will play a crucial role in preventing the suffering caused by this debilitating disease.”
He emphasised that the partnership with Valneva and Instituto Butantan, with “support from the EU”, will ensure the vaccine is accessible to the “people most affected by the virus”. Dr Juan Carlos Jaramillo, Chief Medical Officer at Valneva, echoed this intention.
“Our objective is to make this vaccine available to the largest number of people that will benefit from it.”
Dr Jaramillo reflects that “more than 75%” of the global population lives in “areas at risk” due to factors like “global warming and climate change”. Will Valneva’s vaccine reach these people in time? How do you think the FDA approval might drive further progress for other areas?
In November 2023 BioCina and GPN Vaccines announced that they are expanding their partnership to develop GPN’s proprietary engineered whole-cell vaccine: Gamma-PN. This is a vaccine against Streptcoccus pneumoniae, a bacterium responsible for life-threatening infections. BioCina will manufacture “large-scale cGMP batches” for the programme.
Streptococcus pneumoniae
Streptococcus pneumoniae is responsible for up to 2 million deaths worldwide every year due to infections like pneumonia, bacteraemia, and meningitis. It is a Gram-positive “commensal organism” in the respiratory tract, which means that it can benefit from the human body without causing harm. Humans are the “only known host”. Although it is sensitive to penicillin, there is a growing rate of resistance.
“This leaves vaccination as a critical tool in disease control.”
GPN’s technology is based on a strain that “lacks capsular polysaccharide, is avirulent, and safe to handle”. It is inactivated with gamma irradiation to create the vaccine. This process offers an advantage over other methods as it “maintains the structures of conserved surface antigens” which allows effective induction of protective immunity”.
The partnership
BioCina has a facility in Australia with a “rich history” of working with recombinant proteins in microbial systems, such as E. coli. The company’s CEO, Mark W. Womack, is “extremely proud” of the opportunity to continue supporting production of the vaccine, which “has the potential to protect so many olives against a broad range of serotypes”.
GPN Vaccines’ Chair and CEO Professor Tim Hirst is “delighted” to progress with the next stage of manufacture with BioCina as the “CDMO of choice”.
“They successfully optimised the manufacture of Phase I material, and we now look forward to working with them to deliver a scaled-up process for the manufacture of Phase II material suitable for clinical evaluation worldwide.”
Researchers from the University of Maryland shared in November 2023 that they have made progress in developing a nasal spray vaccine that delivers the SARS-CoV-2 spike protein to cells in the airway. Their research paper, published in Nature communications, reveals that in animal studies this has shown a significant reduction in infection and spread of COVID-19. The team believes that their technology has applications in other respiratory illnesses, such as influenza and RSV.
Target the source
The paper states that SARS-CoV-2 can be shed from asymptomatic infections and spreads “predominantly through droplets and airborne aerosols”. Because the virus “first enters the nose or mouth” and then replicates within the epithelial cells of the nasopharynx, prompting an upper respiratory infection, the nasal mucosa and nasopharynx are the “primary sites of exposure” to the disease before dissemination to other areas.
Current intramuscular vaccines “can effectively prevent severe diseases and deaths”, but do not effectively “elicit protective mucosal immunity in the upper respiratory tract”. Therefore, “opportunistic breakthrough infections” are enabled in vaccinated individuals. Additionally, SARS-CoV-2 can “linger in the nasal mucosa” even after infection has been cleared. The authors suggest that evolutions to the virus necessitate a “safe and protective mucosal vaccine” to “block the viral entry and reduce or eliminate the viral spread”.
The ideal solution would be nasal spray vaccines, which can “elicit local secretory IgA antibodies and resident T and B cell responses in the upper respiratory tract and the lungs”. Furthermore, they are less invasive, with potential to increase vaccine uptake. In their research, the Maryland team determined the ability of a protein called neonatal Fc receptor (FcRn) to deliver an intranasally-administered antigen and induce protective mucosal and systemic immunity to SARS-CoV-2 infection.
Progress in animals
The team administered their vaccine to mice before exposing them to ancient SARS-CoV-2, Delta, and Omicron variants of COVID-19. The mice that were exposed to the Delta variant died, while between 83% and 100% of vaccinated mice survived.
Furthermore, although mice exposed to major Omicron variants survived, there was a significant reduction in inflammation and virus loads in vaccinated mice compared with unvaccinated mice. Another result that comparisons between nasal and injected vaccination revealed a more potent immune response in the airway and lungs for the nasal vaccine.
The results indicate a positive future for FcRn-mediated respiratory immunisation. The study authors describe it as an “effective and safe” strategy to maximise the “efficacy of vaccinations against infection and transmission”.
How do you think nasal spray vaccination could improve our efforts against SARS-CoV-2? Would you be more inclined to receive or administer this technology?
In November 2023 CEPI and the University of Oxford announced a new project to “initiate the early development of prototype vaccines” against the Junín virus. This has been selected as an “exemplar” of the Arenavirus family, with the hope that the resources generated through the project can “give the world a head start” in the development of vaccines against Arenaviruses within 100 days of their identification.
Junín virus
Junín virus is the “causative agent” of Argentine Haemorrhagic Fever, with symptoms ranging from muscular pain and dizziness to rashes. It has a 15%-30% case fatality. CEPI describes it as “endemic to the Pampas of South America”, the fertile lowlands that span over a million square kilometres.
The virus is a member of the Arenaviridae family, “generally spread by rodents”. The family was first identified with the discovery of Lymphocytic choriomeningitis virus (LCMV), isolated in 1933 during a study. Of the 15 arenaviruses that are known to infect animals, 5 cause disease in humans, including Junín virus. Lassa fever is also a member of the family, one of CEPI’s priority pathogens and on WHO’s R&D Blueprint list.
Oxford’s vaccine efforts
CEPI states that the team in Oxford was “able to develop a COVID-19 vaccine with unprecedented speed” partly thanks to their prior research into MERS, a “closely related virus” in the coronavirus family.
“This gave the team a significant head start when COVID-19 emerged because they had solved many of the critical vaccinology problems for coronaviruses in advance.”
In this project, CEPI and Oxford aim to “replicate this approach” for the Arenavirus family by “generating crucial knowledge about vaccine design and biological mechanisms linked to protection”. CEPI will provide up to $25 million for preclinical and Phase I clinical development using the ChAdOx platform, which was the foundation for the Oxford COVID-19 vaccine, and other rapid response platforms.
Responding to a wakeup call
Dr Richard Hatchett, CEPI’s CEO, reflected that COVID-19 was a “wake-up call to the world” and highlighted the “critical need to be better prepared for future viral threats”.
“This new project will harness the University of Oxford’s extensive vaccinology experience and its innovative ChAdOx vaccine technology – one of only a handful of vaccine platforms proven to work at speed, scale, and low cost – to expand the world’ scientific knowledge on Arenavirus vaccines.”
Dr Hatchett intends the project to generate “vital resources” for the “proposed Global Vaccine Library”. Oxford’s Professor Teresa Lambe commented that the project will unite scientists in Oxford and Latin America, working with “both viral vector and mRNA technology”.
“Our work will not only inform best-in-class vaccines against the Junín virus, but it will also support vaccine development for the broader group…It is this wider impact that could crucially help the world develop and manufacture safe, affordable vaccines at speed.”
In October 2023 the European Vaccine Initiative (EVI) announced that it will be coordinating a new partnership to explore how new technologies can offer greater immune insights and develop a next-generation malaria vaccine. The project is called correlates of protective immunity-driven investigation of malaria vaccine combination strategies (CAPTIVATE) and begins in November 2023. Funded by the European Commission, CAPTIVATE comprises partners from four EU countries and Australia.
Malaria efforts
Malaria is a life-threatening disease with an estimated 619,000 deaths in 2021. WHO suggests that in that year there were roughly 247 million cases worldwide, with almost half of the global population at risk. The WHO African Region “carries a disproportionately high share” of the global malaria burden, comprising 95% of cases and 96% of deaths in 2021.
Despite the continued burden, progress is being made in the fight against the disease, and WHO has recommended the use of RTS,S/AS01 and R21/Matrix-MTM. These vaccines are expected to “significantly contribute to malaria control”, suggests EVI. However, there is more to be done.
CAPTIVATE
EVI reports that CAPTIVATE will “complement” global malaria efforts by using “new technologies” to gain a better understanding of immune reactions to malaria and develop the “next-generation malaria vaccine”.
“CAPTIVATE will develop a new and improved vaccine targeting multiple developmental stages of P. falciparum, the most dangerous form of the malaria parasite.”
The consortium, which “assembles a unique combination” of experts in various fields relating to malaria and vaccine development, will “optimise the efficacy of current pre-erythrocytic vaccines” while “evaluating the safety and immunogenicity of new blood-stage mRNA vaccine candidates”. Alongside this, the work will involve the development of a next generation of “highly efficacious malaria vaccine candidates” using an advanced in-silico platform to “analyse TCR- and single cell sequencing data” with AI predictions of vaccine antigens.
The consortium will also establish a European facility to produce malaria sporozoites for “research and clinical use”.
For more insights into partnerships and progress on diseases like malaria, don’t forget to subscribe here. If you’re interested in vaccine development for malaria, you might like to join us in Santa Clara for the World Vaccine West Coast, where Professor Bryce Chackerian will present.
Research published in mBio in October 2023 shows that artificial intelligence (AI) could be used to effectively identify vaccine candidates for gonorrhoea. Using a platform called Efficacy Discriminative Education Network (EDEN), the team of researchers from the USA and Denmark screened 26 gonococcal proteins discovered by EDEN. They combined two to three antigens, adjuvanted with GLA-SE, to form 11 groups for vaccination of mice.
Gonorrhoea
The study reports that Neisseria gonorrhoeae, the “causative agent” of the sexually transmitted infection gonorrhoea, has become resistant to “almost every antibiotic in clinical use”. Alongside the resistance is a concerning increase in cases of gonorrhoea, with a 118% increase in cases reported to the CDC between 2009 and 2021.
“There is an urgent need to develop safe and effective vaccines against gonorrhoea.”
EDEN
Developed to support efforts against the “growing problem of antibiotic resistance”, EDEN is an innovative platform that uses AI to identify antigens that will “trigger a robust, protective immune response”. Antigens are assessed on their ability to elicit this response, with promising candidates progressing before vaccine formulation.
Evaxion Biotech explains that “the core” of this technology is a “proprietary machine-learning ensemble of AI models” that is used to “interpret immunological-relevant information about bacterial antigens that incur protection in vaccine setting”. EDEN has been “trained” on a “curated data set”. Andreas Holm Mattsson, founder of Evaxion, explained to News Medical that EDEN uses a “feature like face recognition” to “understand the difference among proteins”.
Promising candidates
The study identifies two “promising gonococcal vaccine candidates”. Although 8 out of 11 groups showed efficacy against the target strain, MS11, by “at least one of two measures – time to clearance or area under curve”, only a combination of NGO1549 and NGO0265 showed efficacy against H041. The authors report that, coupled with the “broad bacterial activity of sera” obtained from the group, NGO1549 and NGO0265 were selected as “lead candidates”.
EDEN was also used to generate “scores” to predict how well antigen combinations would reduce pathogenic bacterial populations of Neisseria gonorrhoeae. Dr Sanjay Ram of the University of Massachusetts Chan Medical School believes that “this correlation has not been shown before”.
The next steps would be to move the candidates beyond preclinical research to test in humans, but the team is also considering applying EDEN to other pathogenic microbes. How do you think EDEN might revolutionise vaccine development?
In October 2023 CEPI and Moderna announced a strategic partnership to “harness Moderna’s mRNA platform” for vaccine development. The work within this partnership is expected to “expand the infectious disease targets” for the vaccine technology and support the efforts of the 100 Days Mission.
“mRNA technology has been identified as a pivotal enabler of the 100 Days Mission due to its flexibility as a rapid-response platform on which new vaccine candidates can be designed and quickly made ready for clinical testing and subsequent scale-up.”
After the success of Moderna’s “leading” platform during the COVID-19 pandemic, hopes are high for other applications.
An initial project
The organisations state that the partnership will “kick off” with an initial project to evaluate the performance of novel AI-generated antigen designs and mRNA technology “against a range of viral families”. CEPI-funded vaccine researchers will share designs with Moderna’s teams, who will “rapidly” manufacture the related vaccine candidates for preclinical testing, funded by CEPI.
CEPI reports that this project will enable researchers to “swiftly test” multiple antigen designs for a specific viral family. They can then identify any that are promising. Additionally, data will be generated on the performance of the technology against selected viral families, allowing researchers to assess the “suitability and effectiveness” of mRNA for different targets.
“CEPI and Moderna will discuss additional vaccine development projects which fall under the remit of this strategic partnership, with further announcements to follow in due course.”
Preventing pandemics
Dr Richard Hatchett, CEO of CEPI, commented that “future outbreaks are inevitable, but another pandemic is not”.
“Thanks to the scientific and technological innovations advanced during COVID-19, the world now has the tools and capabilities to prevent the next outbreak from spiralling into a global catastrophe.”
One such technology is mRNA, a “proven” vaccine technology. Not only does the platform facilitate the development of “safe and effective vaccines”, but they can be “rapidly manufactured at scale”.
“Our partnership with Moderna will harness the company’s clinically validated mRNA platform and its world-leading team of scientists to help prepare to respond to future epidemic and pandemic threats in as little as 100 days.”
Moderna’s CEO, Stéphane Bancel, is “pleased” to announce the partnership, which will use the “power” of the platform to “accelerate the development of mRNA vaccines”.
“Our mRNA Access programme reinforces our dedication to public health by offering researchers the opportunity to utilise our mRNA technology in the development of vaccines for emerging and neglected infectious diseases.”
Bancel believes the programme can play a “key role” in “helping the next generation of researchers and engineers to advance mRNA science”.
mRNA Access
Moderna’s mRNA Access programme is a means of opening production capabilities and development expertise to partners so that “together” they can explore the “possibility of mRNA”.
“Our mission is to accelerate innovation and enable new vaccines and medicines for emerging and neglected infectious diseases through collaborative research and pre-clinical development.”
In October 2023 the Human Immunome Project (HIP), a global nonprofit organisation dedicated to “decoding and modelling the immune system”, shared a 5-year “Scientific Plan”. The announcement states that from 2024 the HIP will “oversee the generation of the largest immunological dataset in history”. This will be used to create AI models of the immune system for the acceleration of research and discovery. Here we examine the ambitions that HIP is setting for the coming years, to understand what they mean for the vaccine community.
Immune networks
HIP describes the human immune system as a “dynamic, multi-scale network”, involving “uniquely complex interactions” between molecules, cells, and organs. Its role in human health “critical” as it monitors, reacts to, and defends the body against pathogens and stressors. Although we know how important it is to human health, and despite “tremendous advances” in technology, data are “limited in both size and scope”. Thus, “less than one percent of the immunological data necessary to understand immune diversity on a global scale” are “unavailable”.
Without these data, we are prevented from “harnessing the power of the immune system” in pursuit of better human health. To fill in the gaps, HIP will focus on the generation of multi-omic immunological baseline data to reflect the “diverse human population”. This will happen through a “phased approach”.
Phase I
Phase I is divided into 3 main goals. The first is “collect data at pioneering sites”. 7 state-of-the-art collection sites, or Pioneering Sites, will be established to collect “extensive data” from 500 participants. After baseline collection, longitudinal data will be generated to assess “developmental and age-dependent changes” and to “computationally stitch together the temporal trajectory” of different age groups across males and females.
The second goal is to “establish HIP Site Plan for Scaling”. In collaboration with the Pioneering Sites, and reflecting on their experiences, the team will “refine the protocol and site structure”, establishing a replicable site model that can be scaled to up to 100 sites around the globe. The process involves “refining” and developing the required assays, ensuring standardised quality, and prioritising “the most important immune parameters to capture” as data collection is scaled.
“Crucially, HIP will support local capacity building, training personnel in sample collection, first in blood and skin, and then in other tissues.”
A “fleet” of human immunology study sites will be created, as will a “network of global partners”. This goal seeks to ensure that “every corner” of the world is equipped with the “necessary tools”.
The third goal is “engineer Immune monitoring Kit (IMK). HIP identifies a “trade-off between technology maturity and resolution”. In response to “replicability, financial, and universal deployment challenges” HIP is working on an Immune Monitoring Kit to capture standardised and multi-omic data from the population. The kit will “simplify data collection” and “limit cost”.
“Achievement of these three goals during Phase I will substantially increase the amount of immunological data available and will enable the Human Immunome Project to initiate Phase II of our scientific plan, drastically expanding and rapidly scaling data collection worldwide.”
Phase II
Phase II comprises 2 goals. The first is the scaling of study sites: “establish 70-100 data collection sites globally”.
“Our global study protocol and scaled participant number is designed to capture diversity of individuals and thus immune functions and responses.”
Although collections sites will be “highly distributed”, HIP will be “mission control”. This means “overseeing the global network and managing the logistics and scientific strategy”. A Scientific Steering Committee, comprising experts in immunology, AI, and “beyond”, will be responsible for study design and direction.
The second goal is “deploy Immune Monitoring Kit”. This complements the scaling of sites and participants to ensure that data is standardised.
“The Immune Monitoring Kit is central to HIP’s scientific approach as it not only ensures consistent measurements, but also empowers local sites to develop data generation, processing, and storage capacities.”
This is intended to empower lower resource areas with the “same level” of tool as the most “advanced immunological institutes”. The result will be high quality standards and the encouragement of global buy-in and participation.
“Successful execution of Phase II will enable the development of AI models of the immune system that can predict the immune responses and health trajectories of individuals using baseline information.”
5 more years
After the first five years, which focus on data generation and understanding, the next five will be “dedicated to growing the quantitative and predictive models” as well as building the “first-ever, and publicly available, mechanistic, computable models of the immune system”. These will allow insight into response outcomes but also how the immune system operates.
“Such information will transform our ability to programme the immune system to optimise health outcomes, with applications in all areas of health including vaccine development, infectious diseases, autoimmunity, pandemic preparedness, cancer, and neurodegeneration.”
Two further pillars will be added to the plan at the stage.
How do you think this will influence future vaccine design? Will the pillars be a sustainable approach to this data generation? For more on understanding the immune system and tailoring vaccines to human needs, don’t forget to subscribe.
An artificial intelligence (AI) tool developed by a team from the University of Oxford and Harvard Medical School could help predict new viral variants according to findings in Nature in October 2023. The University of Oxford reports that EVEscape, the model, predicts the likelihood that a viral mutation will enable it to “escape immune responses”. EVEscape combines three sources of information to “score” individual mutations:
A deep generative model for fitness protection
Structural information about the spike protein to estimate antibody binding potential
Chemical distances in charge and hydrophobicity between mutated and wild type residues
COVID-19
The research paper states that “extensive surveillance sequencing and experimentation” from the COVID-19 pandemic have presented a “unique opportunity” to assess EVEscape’s ability to “predict immune evasion” before escape mutations are observed.
“The ability of EVEscape to identify the most immunogenic domains of viral proteins without knowledge of specific antibodies or their epitopes could provide crucial information for early development of subunit vaccines in an emerging pandemic.”
Contributing author Associate Professor Yarin Gal believes that the “critical aspect” to the team’s approach is the methods “do not have to wait for relevant antibodies to arise in the population”. DPhil student and co-lead author of the study Pascal Notin commented that “had EVEscape been deployed at the start of the COVID-19 pandemic, it would have accurately predicted the most frequent mutations and the most concerning variants for SARS-CoV-2″.
The study evaluated the model’s ability to make early predictions based on the limited information available at the start of the pandemic. It was able to successfully predict emerging and prevalent mutations as well as which antibody-based therapies would lose efficacy. EVEscape was also effective at predicting immune escape mutations for influenza, HIV, and “understudied viruses with pandemic potential” like Lassa and Nipah.
Vaccine design
The work represents a huge advance in disease control, and Notin suggests that it has “tremendous value” for pandemic surveillance and vaccine design.
“The most exciting next step for this line of work is demonstrating how it can be used in practice to inform vaccine design.”
Associate Professor Gal agreed that “anticipating viral variants that avoid immune detection with sufficient lead time” will be ‘key to developing optimal vaccines and therapeutics”.
“Antibody escape mutations affect viral reinfection rates and the duration of vaccine efficacy.”
In October 2023 the University of Oxford’s Oxford Vaccine Group announced funding from the Medical Research Council within UK Research and Innovation (UKRI) to support a “pioneering” study into human immunity. The study is called LEGACY03 and will investigate how lymph nodes work and contribute to vaccine responses in patients of different ages. This research will potentially inform vaccine design for different age groups.
LEGACY03
The study is open to participation from volunteers between the ages of 18 and 45 and over the age of 65. It will take place at the Churchill Hospital’s Centre for Clinical Vaccinology and Tropical Medicine. Participants will be enrolled for 3 months, with the results supporting better vaccine design for “different age groups throughout life”. Participants will be given two licensed vaccines: an mRNA COVID-19 booster vaccine and a seasonal flu jab.
“As we age, our immune system changes and with it our response to vaccines. Our risk of complications from infections like flu and COVID-19 also increases and it is therefore important to understand these changes so that vaccinations can be better tailored for maximum efficacy to protect the most vulnerable.”
Dr Katrina Pollock, MRC Clinician Scientist in Vaccinology at the Oxford Vaccine Group, Department of Paediatrics, was “keen to improve understanding of the immune system” and respond to the “challenges in adult vaccinology”, which she suggests are “two-fold”.
“The first major challenge is the diversity of responses to vaccines in different people, particularly the most vulnerable like older adults or those living with conditions that affect the immune function. The second major challenge is making vaccines for targets that rapidly evolve, like COVID-19 and HIV.”
Dr Pollock states that the study will “take an innovative look” at individual immune responses, investigating human immunity “at the cellular level”.
“This will help us to tailor future vaccine design to get a better outcome for patients across the board. It has the potential to impact patients for the better and that is what drives my research.”
Lymph nodes
Lymph nodes are “small bean shaped organs” that can be found all over the body. When a vaccine is administered, white blood cells transport some of the vaccine back to the lymph nodes for a response to happen. In this study, the lymph nodes will be visualised with an ultrasound scanner and cells extracted to understand how they are responding. The cells will be sampled using the “safe and well-tolerated” technique, fine needle aspiration (FNA).
