Between two and four years. That is the time it usually takes to prepare a new vaccine such as the SARS-CoV-2 virus, responsible for the COVID-19 pandemic. During that time, multiple clinical trials are carried out with a high number of healthy volunteers. And the vaccine is only considered suitable if good results are achieved in three consecutive phases examining its safety, efficacy, and effectiveness in providing long-lasting immunity, that is, protecting it from the infectious agent for a long time (or a lifetime).
The question that surrounds us all is, can the process be shortened? Yes, partially overlapping the three phases in time. But never under 18 months. Which in the case of COVID-19 means waiting for the spring of 2021.
The three phases of the trials
The first phase The clinical trial of a vaccine examines whether it induces fatal toxicities or serious pathologies in twenty to one hundred healthy volunteers recruited. This phase usually takes at least three months.
It is followed by a second stage in which the immune response against the infectious agent, the doses of the vaccine and the vaccination schedule are evaluated. For this, between 200 and 500 volunteers are recruited. Normally, in this second phase we work with healthy adult volunteers between 18 and 55 years old who have not passed the infection. And in the case of the current COVID-19 pandemic, being the elderly the most vulnerable, includes a group of healthy individuals over 65 years of age.
In both groups of volunteers the complete vaccine is tested. But half of them, chosen at random, are injected with “placebo” instead of the complete vaccine, that is, the formulation of the vaccine without the antigen of the pathogen responsible for the immune response. It is desirable that the volunteers live with the infectious agent to examine whether the vaccine can protect against infection. In the case of the current SARS-CoV-2 virus situation, there are countries in the first wave of infection and others in the second wave. This second phase of trials usually lasts at least six months.
The phase three aims to check the long-term immune response. In this phase, thousands of volunteers are recruited, usually between thirty and fifty thousand people, with the same characteristics and groups as in the previous phase. That is, be healthy and have not passed the infection.
By including a very high number of volunteers, this phase has great statistical value, both for detecting secondary toxicities, which would have gone unnoticed in the previous phase and which are never serious but mild toxicities, and for establishing the efficacy of the vaccine. It is normally required to be greater than 60%, although in the case of COVID-19 WHO proposes requiring only a minimum of 30%, and consider 50% suitable. This phase usually has a minimum duration of six months, although the most common are nine or more.
Taking into account all these phases, the minimum trial time is 15 to 18 months.
Are the announcements of a vaccine for November realistic?
Would it then be possible to have the first COVID-19 vaccine for October or November, as is already heard in different media? If we stick to the necessary phases for approval, no. But it is not recommended either. Among other things, because not only do these phases have to be fulfilled, but also the final evaluation of the results of the last phase by the regulatory agencies and the monitoring of vaccinated individuals must be taken into account.
To make matters worse, once approved, it takes some time to produce the vaccine, pass it through quality controls and detect possible side effects. In the case of the possible vaccine for SARS-CoV-2, to have global coverage with a very high number of doses, it would be necessary to add at least three more months. Although there are already companies that are starting to manufacture it before it goes through all the tests successfully, what if all goes well could also speed up the process.
Therefore, if all goes well with the current phase III vaccines for the COVID-19 pandemic, the most likely dates would be from January or February next year.
The downsides of rushing
Can some Rushed trials affect their effectiveness? If these reasonable timelines of the three complete phases of clinical trials for the preparation of a vaccine are not followed, it is very possible that efficacy will be affected, which discriminates the results between vaccinated and unvaccinated individuals.
At this point, it is convenient to clarify the differences between efficiency and efficacy of a vaccine:
- Efficacy of a vaccine is the percentage reduction in the incidence of an infectious disease in vaccinated individuals compared to the group of individuals who are not vaccinated (placebo group). It is measured in the third phase of the design of a vaccine.
- Effectiveness of a vaccine it is the ability of a vaccine to protect against infection when applied in real conditions, something that is evaluated once clinical trials are completed, with all their phases. That is, it is the evaluation that is made once it is marketed. Which is also important.
Furthermore, the rush could prevent an assessment of why sufficient protection is not achieved in some subjects, whether there is a genetic reason for this, or whether the vaccine formulation can be modulated to achieve universal adequate protection.
By speeding up the process, neither the secondary toxicities nor the scientific reasons for these toxicities can be well evaluated. The latter would be especially important for individuals with certain pathologies (diabetes, severe chronic or respiratory cardiovascular diseases or cancer), which in the case of the SARS-CoV-2 virus are high risk and candidates for vaccination in the early stages.
In summary, the times to prepare a vaccine against an infectious agent that poses a great global challenge can be shortened. But always within limits that do not determine the efficacy, effectiveness, or safety of all possible candidates for vaccination.
Carmen Alvarez Dominguez is a Biochemist and molecular biologist, professor of Health Processes at the Faculty of Education and researcher in Immunotherapy, UNIR – International University of La Rioja.