Interview on COVID-19 with Professor Rino Rappuoli, Head of External R&D at GSK Vaccines) and Professor Sarah Gilbert, Jenner Institute Vaccine Development, University of Oxford.
In your opinion, which part of the vaccine production process is the biggest challenge and why?
Prof. Sarah Gilbert : The challenge is getting funding in place in time to react quickly enough. It is essential not to miss the opportunity to test vaccine efficacy before a large percentage of the population have already been infected. That means being ready to vaccinate thousands of people by July, and in order to get to that point the vaccine has to be manufactured, tested for safety I pre-clinical studies, receive ethical and regulatory approvals for phase I and then move through testing safety and immunogenicity in young adults, then older adults, and then determine vaccine efficacy. If we miss this window of opportunity, vaccine efficacy trials will need to be much larger as more people will be immune and there will be less virus circulation in the population.
Prof. Rino Rappuoli : Today, starting from the sequence of the virus, the new technologies make possible to make a vaccine for laboratory testing in one week. The challenge comes later in proving in the laboratory and the clinic that the vaccine is safe and effective. Finally the biggest challenge in terms of time and investment is the industrialization of the process to manufacture the vaccine, the construction and validation of a manufacturing facility able to make the vaccine in large scale.
Is developing a vaccine with efficacy against all SARS-CoV possible?
Prof. Rino Rappuoli : In theory this is possible, however this will require time and focused investment.
Will vaccination be available and suitable to all ages?
Prof. Sarah Gilbert : That is the aim. But in older adults with a less effective immune system the vaccine may not work as well as in younger adults.
Why does vaccine development process for SARS-CoV-2 take so long and why there is no available vaccine yet, since SARS-CoV-1 emerged in 2003?
Prof. Rino Rappuoli : COVID is a new virus, and although it is 79% homologous to SARS, in immunological terms they are quite different and a vaccine for SARS is not effective against COVID.
Prof. Sarah Gilbert : The vaccine is expected to be specific for SARS-CoV-2, but there may be some cross-reactivity against SARS-CoV. For the highest level of vaccine efficacy it appears likely that two separate vaccines would be needed to protect against both viruses. Initially development of vaccines against SARS-CoV did not progress very far and stopped when the outbreak was contained. It was found that alum adjuvanted inactivated SARS-CoV used as a vaccine actually made the disease worse when animals were vaccinated and then infected, so that is not a suitable approach to take. Since that time a number of vaccine platform technologies (DNA, RNA, viral vectors) have come into use and theses are now being tested for SARS-CoV-2 vaccines to ascertain that the same issue does not arise.
How long does it take for the vaccine to become effective and could currently ill patients be vaccinated?
Prof. Sarah Gilbert : It depends on the vaccine. For the viral vectored ChAdOx1 vaccine we are producing in Oxford, we expect to initiate strong and protective immune responses with a single dose, and within 2 weeks of vaccination the immunity will be present. Other vaccines (DNA, RNA) are likely to require two doses given four weeks apart, with protective immunity developing after the second vaccination. It is not expected that currently ill patients would benefit from vaccination but infusion of monoclonal antibodies, sometimes described as passive immunisation, could be used as a therapy.