Day1

Efforts addressing the COVID-19 pandemic: need to continue

Agile management and inclusion of all stakeholders was the key to the UK vaccine task force’ success in effectiveness (https://www.gov.uk/government/publications/the-vaccine-taskforce-objectives-and-membership-of-steering-group). The task force consisted of representatives from industry, academia, government, clinical trial organizations and manufacturers. Decisions leading to its effectiveness had sometimes to be courageous, said Dr Jonathan Van Tam, UK Department of Health, in his keynote address on the UK Covid-19 vaccination programme – from strategy to delivery. He also emphasized that tiredness of the pandemic is no option and all efforts addressing it, need to continue.

Global mission against inequity of COVID-19 vaccination

During the keynote panel on efficacy data from COVID vaccines and preparedness for variants some very straight forward statements from the representative of WHO, Kate O’Brian, made it clear that we have enough vaccine to vaccinate the world, but it is not well distributed. The pandemic is a global issue and one country cannot protect itself. A global mission against inequity long-term is needed to fight the pandemic (https://www.who.int/news-room/q-a-detail/coronavirus-disease-(covid-19)-vaccine-access-and-allocation?adgroupsurvey={adgroupsurvey}&gclid=CjwKCAjwq9mLBhB2EiwAuYdMtd8L4SsKGUliDJqAZ8KfnLtkDyN9uEBnydgYrpxZGIswobg6gc4kexoCtMIQAvD_BwE ).

A universal coronavirus vaccine

The interactive roundtable “Is it feasible to develop a universal/pan coronavirus vaccine” was met with great interest. The question asked was whether this was a tempting idea or just a dream (see also Variant-proof vaccines — invest now for the next pandemic, https://www.nature.com/articles/d41586-021-00340-4). There was no clear-cut answer to the question, but on the other hand, can we afford not to attempt to develop one? Experience with different types of RNA virus indicate both the possibility (Measles vaccine) or the impossibility (Influenza vaccines) for success in developing such a vaccine. Also, the worst case, that is, the need for a new vaccine for every new variant is also an option, as is the case for Polio- and Rhinoviruses.

The ideal solution for COVID-19 of course would be, if a new highly transmissible attenuated wild type variant would act naturally as vaccine against the virulent strains, as has been the case with Transmissible Gastroeneritis Virus (TGV) in pigs. Such a course of action seems rather unlikely for SARS-CoV-2, though.

The future evolution of SARS-CoV-2; how will it evolve as it establishes itself in the human population?

How to plan for the future is still an open question (see also Ongoing global and regional adaptive evolution of SARS-CoV-2, https://www.pnas.org/content/118/29/e2104241118). RNA virus have very different patterns of behavior, that is, stability versus variation. Some linages of Influenza, for example, disappeared, but of Rhinovirus multiple lineages exist. Based on sequence data of SARS-CoV-2 many strictly new lineages seem to have gone extinct and replaced by others. The delta variant has outcompeted all other variants, also the more pathogenic variants, based on its high transmissibility. So might the virus have reached its peak regarding competitive variants, that is, do new variants not have much chance against the current delta variant? At least for vaccination, this would be a great advantage.

Effectiveness of heterologous prime boost regimens of COVID-19 vaccines

It has been demonstrated that regimens combining two different COVID-19 vaccines are highly effective at preventing the disease and they protect against the Delta variant (Schmidt et al., 2021, Nature Medicine,https://www.nature.com/articles/s41591-021-01464-w). Heterologous prime boost regimens have been tested by COM-COV with positive results for both antibody- as well as T-cell response (https://www.ox.ac.uk/news/2021-09-17-com-cov-vaccine-mix-and-match-study-expands-12-16-year-olds ). Interestingly, anti-vector immunity did not decrease boost response vector vaccines. However, at the moment, there seems no real-life evidence yet that boosting vaccinated persons is needed or increasing protection.

Globalization of infectious disease and loss of biodiversity

The question asked at this session was not whether a new infectious disease would occur in the coming years, but by which virus. 10 of 24 emerging disease outbreaks are of zoonotic origin. Biodiversity loss was considered as an important driver. El Nino seemed to have fostered spread of ZIKA virus from Brazil to all of South America. By 2080, it is expected that 1 billion people will be affected by mosquito-borne diseases, including Europe and East Africa. (see also how biodiversity loss is hurting our ability to combat pandemics by the World Economic Forum 2020, https://www.weforum.org/agenda/2020/03/biodiversity-loss-is-hurting-our-ability-to-prepare-for-pandemics/).

Immune responses to SARS-CoV-2 in children

As summarized by Arnaud Diderlaurent of the University of Geneva (https://www.unige.ch/medecine/pati/fr/groupes/1025didierlaurent), children do have less sever COVID-19 symptoms and less symptoms, all together. While still having very high viral loads and no delayed shedding, children eliminate the virus much faster than adults. They show the typical gene signature of SARS-CoV-2 infection, a text book inflammatory response, so to speak, but with a very early anti-viral response. Practically after one week, SARS-CoV-2 in children is gone, due to a strong local response in the nose/upper respiratory tract. The inflammatory monocytes seem to be much higher and the enrichment of B-cell response much earlier than in adults. The question was raised though, whether this reaction was due to the fact that children have less antibodies against the common cold Coronavirus than adults.

Day 2

Should we be vaccinating children with the new COVID vaccines & what is our strategy with other population/age groups? (immunocompromised children)

The second day started with a keynote panel discussion on the question whether children should be vaccinated, looking at the value from a population health perspective.

The benefit of vaccination was considered as rather low, that is prevention of hospitalization of 87 children in 1 Mio children after the first dose and somewhat higher after the second dose. Uncertainty prevailed over the dose needed for children. Whereas the need of vaccination of children at low risk was not given, vaccination of immunocompromised children was favored, because these children and also their parents would benefit a lot from the resulting psychological liberation. From a political point of view, there was a feeling that vaccine doses should first be used for at risk adults and all those not having access to vaccination, prior to vaccinating children.

Should we be vaccinating children with the new COVID vaccines & what is our strategy with other population/age groups? (immunocompromised population and pregnant women)

Much of the discussion during the panel encompassed vaccination of the immunocompromised population and pregnant women. It was made very clear that the immunocompromised even if they showed very limited or no serological response to the vaccine, still had a T-cell response and a third dose might be valuable. In any case, for these individuals, a booster vaccination was far less dangerous than having COVID-19.

Also, based on clinical data, it seemed evident that vaccination of pregnant women was important as with COVID-19 there was an increase in preeclampsia (improper functioning of the placenta including insufficient blood flow to the placenta), pre-termed birth and maternal mortality, even in case of asymptomatic disease (see also https://www.unicef.org/rosa/stories/covid-19-and-pregnancy).

Role of vaccines to address antimicrobial resistance (AMR)

WHO presented its strategy to leverage vaccines to reduce antibiotic use and prevent antimicrobial resistance (https://www.who.int/publications/m/item/leveraging-vaccines-to-reduce-antibiotic-use-and-prevent-antimicrobial-resistance). Vaccines could reduce the burden of disease as could be demonstrated by the typhoid vaccine against highly resistant strains in Pakistan. The WHO priority pathogen list is based on the evaluation of the health burden, economic burden, average antibiotic use, sense of urgency and impact on equity and social justice. In order to prioritize the need for vaccines, one would have to understand the disease landscape and estimate the value of a vaccine and the impact on a given country. Goals of the strategy are to prioritizes the need for vaccines based on the evidence of impact against AMR, articulate value and technical feasibility.

A fully personalized COVID-19 vaccine made at point-of-care

An intriguing approach for conferring personalized immunity against SARS-CoV-2 was presented by AIVITA Biomedical (https://aivitabiomedical.com/programs/sars-cov-2/). This approach includes taking blood from a person to be vaccinated, exposing the dendritic cells of this blood samples to SARS-CoV-2 spike protein and after a 7 day period of incubation reinject to ‘primed’ blood back into this person. The advantage of such an approach was described as not needing a cold chain or specific knowledge as it was provided in a kit which, in addition, was easy to be produced and thus could be produced anywhere.  It was claimed that based on clinical studies, this type of vaccination was 96% efficacious.

One health: Combatting Nipah virus: Developing a vaccine for pigs

Taking into account the need for one health approach, some presentations addressed development of animal vaccines. Dalan Bailey, representing The Pirbright Institute, elaborated on the importance of a Nipah virus vaccine because the virus might not be limited to the known endemic area of its reservoir, the fruit bat (https://www.pirbright.ac.uk/development-nipah-virus-vaccine-pigs). Different interesting approaches for vaccine development are persued such as introducing the sequence of the Nipah virus glycoprotein, NivG, to different vector backgrounds, such as chimpanzee adenovirus (ChAdOx), canarypox virus (ALVAC), Bovine Herpesvirus (BoHV-4) and Hendra virus (HeV) as well as mRNA.

TB vaccine: where are we?

Ann Ginsberg of the Bill and Melinda Gates Foundation made a very interesting comparison between TB and COID-19: Whereas of TB 10 Mio People get newly infected with TB and 1.9 mio die, 20 mio people got infected with SARS-CoV-2 per year and 2-3 Mio people died in 2020. Yet, only one TB vaccine is authorized and 14 in clinical trail whereas 22 COVID-19 vaccines are authorized and 104 currently in clinical trials with an investment of 0.117 Bio $ for TB and 107 Bio £ for COVID-19. Background information on the TB vaccine roadmap is available through the Amsterdam Institute for Global Health & Development (https://www.aighd.org/).

One health: Rift Valley Fever developing the world’s first vaccine suitable for humans and livestock

Neither a vaccine nor a therapy exists for this virus which was detected in Kenya in 1931. It is transmitted by mosquitos or infected animals but no human to human transmission is known. George Warimwe of the University of Oxford Center for Tropical Medicine and Global Health (https://www.tropicalmedicine.ox.ac.uk/team/george-warimwe) reported on the vaccine developed on the basis of ChAdOx. It’s goal was a vaccine being effective for multiple species. Studies in mice showed 100% effectiveness. Studies with sheep, goats and cattle from farmers in Kenia have demonstrated development of antibodies and 100% survival after challenge. A Phase I clinical trial will start in Uganda.

Day 3

How can we better collaborate with a one health approach to prepare for the next pandemic?

One of the most important statements was that a one health approach is needed to address emerging disease X. There was no doubt that the next disease X is out there, and in our lifetime. Therefore, surveillance and detection at the source was considered crucial together with research and development of diagnostics, therapeutics and vaccines. What is disease X? Most certainly a respiratory disease, an influenza virus, but also a mosquito-spread or hemorrhagic diseases were suggested. In addition mentioned were also Ecoviruses with high affinity to humans or any other viral generalists with a broad group of hosts. Preparedness and readiness should be a constant as well as the continued investigation of animal / human interface. Preparatory actions include looking into sequence and immunogen libraries of viral families n order to increase knowledge of a given family. This includes sequencing of virus from different geographic and subnational regions.

Ready in 100 days to face disease X is the goal.

Therapeutic hepatitis B program

Vaccitech, represented by Thomas Evans, reported about their latest results on HBV vaccine development (https://www.vaccitech.co.uk/vaccitech-doses-first-patient-in-hbv002-a-phase-1b-2a-clinical-trial-of-vtp-300-immunotherapeutic-candidate-for-chronic-hbv-patients/). Interestingly, a consensus sequence of the polymerase of all genotypes is used.

Progress with malaria vaccination

Drian Hill of The Jenner Institute of the University of Oxford reported on promising results with a vector like particle type of Malaria vaccine, R21/MM, using the Novavax adjuvans Matrix-M (https://www.jenner.ac.uk/research/infectious-diseases/malaria-vaccine-programme). Tha vaccine seemed to demonstrate 77% efficacies and the highest efficacy ever when applying just before the Malaria season. The Serum Institute of India seems t be ready to produce 200-300 Mio doses. To be noted, the number of death from Malaria was 4 times