For its 2020 to 2023 term of office, the Standing Committee on Vaccination (STIKO) at the Robert Koch Institute has 18 members, and two of them are from Universitätsklinikum Erlangen: Prof. Dr. Christian Bogdan, Director of the Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene, and Prof. Dr. Klaus Überla, Director of the Institute of Clinical and Molecular Virology. In their position as members of the STIKO, the two researchers from Erlangen are involved in drawing up a Covid-19 vaccination strategy for Germany. It may even be finalised this year.
The STIKO issues vaccination recommendations for the whole of Germany. It is an independent committee of experts, coordinated and supported by the office of vaccination and prevention at the Robert Koch Institute. The STIKO can only recommend a vaccine once it has been approved by the European Medicines Agency (EMA) and the German Paul-Ehrlich-Institut (PEI), in other words once phase III clinical trials have proven that it is effective, safe and manufactured to a high standard. The committee not only weighs up the risks and benefits for the health of the individual, but also assesses vaccines on the basis of their impact on the population as a whole.
Working group ‘Covid-19 vaccine’
In the STIKO working group ‘Covid-19 vaccine’, Prof. Bogdan and Prof. Überla are doing the groundwork in preparation for a national vaccination strategy. The working group not only includes virologists and microbiologists, but also paediatricians, general practitioners, representatives from local health authorities, ethicists, statisticians and other experts.
‘In the working group, we analyse the comprehensive literature currently available on Covid-19. We focus predominantly on what we hope to achieve with the Covid-19 vaccine and who should be vaccinated,’ explains Prof. Bogdan, who has been a member of STIKO since 2011. The working group draws up a recommendation which is then submitted to the entire STIKO for approval. Amendments can be made at any time, providing the working group with neutral feedback. After approval, the resolution is submitted to the Federal Joint Committee of Health Insurance Providers (G-BA). The Joint Committee then decides whether the vaccine should be included in the vaccination guidelines, making it eligible for reimbursement by health insurance providers.
‘We are positively surprised’ – first vaccine will probably be approved by regulators in December 2020
The Covid-19 working group of the STIKO currently meets online once every two weeks. The working group meets far more often now than it did before the coronavirus pandemic. ‘I believe that one or more of the Covid-19 vaccines will be approved in December 2020 and that we will publish our strategy shortly. We can probably start rolling out our vaccination programme at the beginning of 2021,’ estimates Prof. Bogdan.
The procedure this time is rather different from usual. Normally, STIKO only assesses a vaccine once it has already been approved by regulators. ‘In the past, it has taken maybe 10 to 15 years for a vaccine to be developed,’ explains Prof. Überla, who has been a member of STIKO since 2017. The coronavirus vaccine is different. STIKO is evaluating the vaccines whilst they are still in the process of being approved by EMA and PEI. The timescale for a number of administrative and decision-making processes has been cut drastically.
‘We don’t want to lose any time. Nevertheless, we are not going to just rubber-stamp any proposed vaccine,’ Prof. Bogdan says, reassuringly. He continues, however, that the figures regarding effectiveness appear ‘very promising’ at this stage. ‘Three different manufacturers have now reported efficacy rates of 90 percent and above, which we were pleasantly surprised about.’ The influenza vaccine, for example, offers a much lower efficacy rate of only 50 to 60 percent, depending on the season. ‘All the same, we still have to weigh up the benefits and risks carefully for the coronavirus vaccine just like any other vaccine. Nothing has changed in respect to the rules and safety requirements, in spite of the speed at which we have progressed,’ Prof. Bogdan continues.
Different vaccines may be approved for different groups of people
The data from clinical phase I and phase II trials with the first vaccine candidates are already available, and STIKO hopes to receive the results from the phase III trials shortly. The current phase III trials are aimed at checking whether those given the vaccine produce neutralising antibodies against the virus SARS-CoV-2 and whether participants display a specific immune response triggered by T-lymphocytes, a certain type of white blood cell.
‘The studies record how many Covid-19 infections there are in those who have been given the vaccine compared to a control group who have not been given the vaccine. This allows us to assess the effectiveness of a vaccine,’ explains Prof. Überla. ‘When STIKO receives the results of the trials, we check whether there is sufficient proof that the vaccine is effective and safe and whether the benefit of the vaccine for the population as a whole is such that we can make a recommendation. We must also decide which group of people should receive the vaccine, or who should be vaccinated first. Our overriding priority is to provide the best possible protection to those groups which are most at risk like the elderly and people with underlying conditions, and to curb the spread of the virus.’
The STIKO may be required to evaluate more than one approved vaccine, and different vaccines may be recommended for different groups of people. As it will take a number of months before a large proportion of the population has been immunised, the Erlangen experts warn against being lulled into a false sense of security. ‘A vaccine does not mean that we will be able to throw all the hygiene measures to the winds overnight,’ emphasises Prof. Bogdan. ‘In the first instance, we will only be able to protect a certain section of the population and will then need to see how well the production and distribution of the vaccines and the immunisation programmes are progressing.’
‘Personally, however, I hope that we as a society will manage to protect 90 percent of those who are most at risk within 90 days of a vaccine offering effectiveness of at least 90 percent being approved. These are what I call the 90-90-90 targets of the Covid-19 vaccine,’ explains Prof. Überla. ‘This would help us avoid a significant proportion of Covid-19 deaths and prevent the health system from becoming overwhelmed. Once these goals have been reached, we can re-think the contact reduction measures, taking the many negative consequences of these measures for each individual, the economy and society as a whole into consideration.’
Keeping a detailed record of side-effects. ‘Long-term side-effects are very rare.’
The good thing is that phase III trials for the coronavirus vaccine are of a considerably larger scale than many of the vaccines which have been approved in the past. ‘We are already talking about 43,000 people who have received one of the Covid-19 mRNA vaccines during a phase III trial. Researchers carrying out phase III trials for one of the adenovirus-based Covid-19 vaccines even plan to test the vaccine on up to 60,000 people. Using groups of this size allows us to recognise rare side-effects, such as those that only affect fewer than one in 1,000 people given the vaccine. We also have to be careful to check whether the side-effects are in fact caused by the vaccine or if they just happened to arise at the same time the vaccine was given. That is why it is so important to keep detailed records of any adverse events which may possibly be connected to the vaccine over a long period of time,’ explains Prof. Bogdan. ‘At the end of the day, we always have to weigh up the benefits against the risks. We will only be able to observe very rare side-effects once the vaccine has been used for a longer period of time and we are able to conduct observational studies. Long-term side-effects are, however, extremely rare. Most adverse effects arise two to three weeks after vaccination,’ adds Prof. Überla.