Covid-19 vaccination strategies

Fanny Trifilieff: How does a vaccine work?

Étienne Decroly: The principle of a vaccine is to present the immune system with pathogen (or antigen) proteins in order to trigger an immune response. This leads to the production of antibodies capable of neutralizing the infection, and of cells capable of recognizing other infected cells. There are various biotechnological platforms for producing vaccines. Some technologies have been around for decades, enabling the production of inactivated or highly attenuated vaccines. With the advent of biotechnologies, new means of production have been developed. These platforms have been designed to optimize vaccine safety through the use of recombinant proteins or RNA vaccines. But the principle remains the same, whatever the platform: by presenting pathogen antigens to the immune system, we prepare it to fight effectively against SARS-CoV-2.

F.T: The development of a vaccine goes through several phases. How did the development of Covid-19 vaccines proceed so rapidly?

E.D: Several factors have played a decisive role in the rapid response to Covid-19. Firstly, over the last 20 years, "vaccination platforms" have been developed. When a pathogen emerges and we have its sequence, we can produce candidate vaccines very quickly. The second factor is the public health emergency. Instead of cascading Phase I, II and III clinical trials, the phases have been overlapping. Phase I involves testing the vaccine on around 50 healthy people to test the safety of the preparation. Phase II is tested on around 500 people to determine how to induce a good immune response (number of injections, quantity, spacing between doses). This helps guide the choice of vaccine strategy for Phase III, which aims to demonstrate vaccine efficacy. It is based on groups of 20 to 40,000 patients. By comparing disease onset between the placebo and vaccine groups, it is possible to demonstrate vaccine efficacy. To obtain statistically significant results quickly, the people selected must be in areas of intense virus circulation. In the case of Covid-19, since the virus circulates widely, vaccine efficacy responses have been very rapid.

F.T: Can the appearance of variants lead to complications in terms of vaccination?

E.D: If we compare the different vaccines currently available, there are two opposite scenarios. In the case of measles, one injection provides lifelong protection. In contrast, vaccination against the influenza virus is annual, as the virus evolves rapidly. In the case of SARS-CoV-2, the appearance of variants linked to the immunity developing in populations suggests that vaccines will need to be progressively adapted to the variants circulating. But with the development of immunity, we can hope that sufferers will develop less severe forms of the disease. The pharmaceutical industry is already working on the development of multivalent vaccines, capable of presenting different variants to the immune system. The more a virus circulates, the more opportunities it has to mutate. If we want to control the virus, we need to combine vaccination with all available means to limit circulation as much as possible. The more we control virus circulation, the fewer variants there will be, and the more effective vaccines will remain.

To find out more, see the seminar given by Étienne Decroly on February 8, 2021 (in French).