Adults who received at least 3 doses of mRNA Covid 19 vaccine (BioNTech-Pfizer and/or Moderna), the last dose received at least 6 months prior to the inclusion in the trial.
Conditions
Interventions
Trade Name: Comirnaty Original/Omicron BA.4-5
Product Name: Comirnaty
Pharmaceutical Form: Dispersion for injection
INN or Proposed INN: cOVID-19 mRNA vaccine (nucleoside-modified)
Other descriptive
Sponsors
Assistance Publique – Hôpitaux de Paris (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18 years and over 2. Adult in a healthy condition or with a stable health status, determined by medical history, targeted physical examination and clinical judgement of the investigator to be in stable state of health. Participants with pre-existing stable chronic medical conditions defined as condition not requiring significant change in therapy or hospitalization for worsening disease within 4 weeks from enrollment can be included at the discretion of the investigator. 3. For women of childbearing age: a negative highly sensitive pregnancy urinary test during the inclusion visit 4. Confirmed receipt of at least three doses of COVID-19 mRNA vaccine the last dose at least 6 months prior to study vaccine 5. Understands and agrees to comply with the study procedures 6. Written informed consent signed by both the participant and the investigator 7. Subject affiliated to the French Social Security System. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 86
Exclusion criteria
Exclusion criteria: 1. Acute febrile infection (body temperature = 38.0°C) within the previous 72 hours and/or presenting symptoms suggestive of COVID-19 within the previous 28 days 2. Confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 10 mg prednisone equivalent/day (excluding topical preparations and inhalers) within 3 months prior to inclusion or within 6 months for chemotherapies. 4. Treatment with immunoglobulins or other blood derivatives within 3 months prior to inclusion or scheduled administration of immunoglobulins or blood derivatives before the end of the study. 5. Any medical condition, such as cancer, that might impair the immune response. 6. Use of experimental immunoglobulins, experimental monoclonal antibodies or convalescent plasma is not permitted during the study. 7. Pregnancy or breastfeeding currently ongoing 8. History of severe adverse events following vaccine administration including anaphylactic reaction and associated symptoms such as rash, breathing problems, angioedema, and abdominal pain, or a history of allergic reaction that could be triggered by a component of the SARS-COV-2 vaccine at the time of the first vaccine injection 9. Any bleeding disorder considered as a contraindication to an intramuscular injection, 10. Participation in other interventional research involving humans within 4 weeks prior to the inclusion visit, or participation in any other vaccine trial excepted for those with mid or long term follow up when vaccination was made at least 4 weeks before the injection in the study. In this case no delay is required after the end of the study participation. 11. Subject under legal protection (e.g. guardianship)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the immune response induced 28 days after a booster dose with the Beta-variant recombinant protein booster vaccine (VidPrevtyn® Beta, Sanofi) with that of a bivalent mRNA vaccine (Comirnaty Original/Omicron BA.4-5, BioNTech-Pfizer), in adults previously vaccinated with at least 3 doses of COVID-19 mRNA vaccine, the last dose received at least 6 months prior the inclusion in the study.;Secondary Objective: 1.To compare in each arm: a) The early immune response at D15 after the boost. b) The persistence of the immune response at M3, M6 and M12 after the boost. 2.To described in each arm the local and general reactogenicity of the booster dose. 3.To describe the factors and determinants of humoral response 4.To explore the breadth of T and B cellular immune response in the two groups and their relationship with the early ASC response (ancillary studies). 5.To describe Covid 19 incidence in each group 6.To constitute a biobank to evaluate seroprotection conferred by the 2 booster vaccines against future emergent SARS-CoV-2 variants.;Primary end point(s): There will be a coprimary endpoint: Neutralizing antibody titers against the SARS-CoV-2 variant of most prominent public health interest according to pandemic evolution (among D614G, B.1.351, Omicron sub-variants BA.4-5, BQ1.1 and XBB or another recent variant) and against one of the targeted variant by the vaccines. The two variants will be specified in the statistical analysis plan before D28 data base lock. Neutralizing antibody titers will be measured by a microneutralization technique 28 days after the booster dose.;Timepoint(s) of evaluation of this end point: 28 days after the booster dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Humoral immune response: 1.1. Neutralizing antibody titers a) Neutralizing antibody titers against SARS-CoV-2 D614G, and variants B.1.351, Omicron sub-variants BA.4-5, BQ1.1 and XBB (or another recent variant of prominent public health interest according to pandemic evolution), measured by a microneutralization technique, at D15, M3, M6 and M12 after the boost. b) Seroresponse rate in each group. Seroresponse is defined as a 10 fold or greater rise in serum neutralization titer at each follow-up time (D15, D28, M3, M6 and M12) relative to D0. 1.2. ELISA: Anti-Spike IgG levels expressed as BAU/mL, according to WHO recommendations, at D0, D15, D28, M3, M6 and M12 after boost. 1. 3. LUMINEX: a) Antibodies to CTD domain of the SARS-CoV-2 N protein to detect recent natural infections at D0, D15, D28, M3, M6, M12 (quantitative arbitrary units). b) Full length Spike protein expressed as BAU/mL) c) Antibodies to RBD of Wuhan, B.1.1.7 (Alpha), B.1.617.2 (Delta), B.1.351 (Beta), Omicron BA.1/2/5, BQ1.1, XBB and others variants according to pandemic evolution at D0, D15, D28, M3, M6, M12 (quantitative arbitrary units). 2. Number and intensity of adverse events of any degree of a) solicited local and systemic adverse events occurring up to day 7 after administration of the booster dose (assessed from the list of solicited adverse events); b) unsolicited adverses events up to 28 days after administration of the booster dose; 3. Factors of interest are age, gender, previous SARS-COV-2 infection, time interval between the last dose and the booster dose, and vaccine boost type 4. Cellular immune response: a) ELISpot IFN-IL-2 CD4 and CD8 response at D0 and D15 (ancillary analysis) against D614, and variants B.1.351, Omicron BA.5, BQ1.1 and XXB b) Repertoire analysis of Memory spike specific B cells and early ASC response. 5. Number of Covid 19 cases (symptomatic with PCR or Ag positive tests or asymptomatic with anti NP antibodies increase from D7 to M | — |
Countries
France
Contacts
Public ContactChristophe AUCAN
Assistance Publique – Hôpitaux de Paris (AP-HP)
Outcome results
None listed