Immunogenicity and Reactogenicity Following a Booster Dose of COVID-19 mRNA Vaccine (Pfizer-BioNtech) and Two Adjuvanted Sub-unit Vaccines (SP/GSK) Administered in Adults Who Received 2 Doses of Pfizer-BioNTech mRNA Vaccine as a Primary Vaccination

The efficacy of COVID 19 vaccines for reducing the risk of severe COVID-19 infection has now been demonstrated in real life. In France, the vaccination campaign started on December 27th, 2020 and was launched rapidly for healthcare professionals and for individuals at risk of severe COVID on January 2021. On August 5th 30th, 2021, approximately 60% of the population (\> 12 years) had already received complete vaccination. Out of approximately 74,3 million doses of vaccine administered, 58 million doses are Pfizer BioNTech vaccine (78%). Data currently available on the persistence of immunity on the one hand and the appearance of viral variants with reduced sensitivity to vaccine immunity on the other, raise the need to administer further additional dose at an interval from the primary vaccination that remains to be defined, possibly different according to age and co-existing diseases. Currently, the only data published are related to the administration of a third dose (booster) of the same vaccine as the one used for primary vaccination. However, some vaccines developed more recently could be an interesting alternative for booster dose in terms of reactogenicity, availability, cost and acceptance. Moreover heterologous vaccination could be more immunogenic than homologous scheme. The vaccine developed by Sanofi Pasteur is based on a conventional adjuvanted recombinant protein approach. Two prototype vaccines are under development, one based on the Spike protein of the SARS CoV-2 D614 strain, the other on the B.1.351 strain. Their interest as booster vaccines needs to be investigated. The objective of this trial is to assess the response induced by a booster dose of either recombinant protein-based subunit vaccine (targeting D614 strain or B.1.351 strain) or by a booster dose of Pfizer-BioNTech mRNA vaccine (targeting Wuhan strain) in individuals previously vaccinated with 2 doses of Pfizer-BioNTech mRNA vaccine. These results will provide important information for booster vaccination recommendations. Participants enrolled will be healthy adults with no medical history of COVID-19; they will be recruited in 10(15?) centers in mainland France, via the COVIREIVAC network. The study will be a randomized, single-blinded, multicentre trial with three parallel arms: ARM 1 receiving Pfizer-BioNTech vaccine * Group 1.A: 18-64 years old * Group 1.B: 65 years and older ARM 2 receiving SP/GSK subunit D614 vaccine * Group 2.A: 18-64 years old * Group 2.B: 65 years and older ARM 3 receiving SP/GSK subunit B.1.351 vaccine * Group 3.A: 18-64 years old * Group 3.B: 65 years and older Participants will undergo 5 visits : * V1 (D0): inclusion, randomization, pregnancy test, PCR test, blood draw and administration of the booster dose * V2 (D28): follow-up visit with a review of solicited and unsolicited local and systemic reactions that occurred since the last visit, and blood draw * V3 (D90): follow-up visit with review of potential adverse events and blood draw * V4 (D180): follow-up visit with review of potential adverse events and blood draw * V5 (D365): follow-up visit with review of potential adverse events and blood draw Blood samples will be used to conduct immunological analyses, and cellular analyses for a sub-category of 26 participants per group.