safety and immunogenicity of a sub-unit protein cd40.rbdv bivalent covid-19 vaccine, adjuvanted or not, as a booster in volunteers.

Conditions: COVID-19

Summary: the goal of this clinical trial, on healthy volunteers, is to learn more about safety and reactogenicity of the cd40.rbdv vaccine. the main questions that will be studied are : * is the cd40.rbdv (adjuvanted or not) safe ? * does the cd40.rbdv (adjuvanted or not) imply an immunologic response ? participants will receive, depending on their randomization arm, 1 or 2 injections of the cd40.rbdv vaccine or a single injection of approved mrna vaccine

phase 1/2a randomized, multicentre trial with four cohorts of two arms in two parts. part 1: cohort 1: low dose (ld) cd40.rbdv vaccine non adjuvanted or mrna vaccine (5:1 ratio) cohort 2: ld cd40.rbdv vaccine adjuvanted or mrna vaccine (5:1 ratio) cohort 3: high dose (hd) cd40.rbdv vaccine non adjuvanted or mrna vaccine (5:1 ratio) cohort 4: sc injection of hd cd40.rbdv vaccine adjuvanted or mrna vaccine (5:1 ratio) a substancial amendment (january 2025) has removed the randomisation to mrna vaccine from the study design go-criterion for opening enrolment within cohorts are detailed into the protocol. part 2 at month 3 : group 1: volunteers who received mrna vaccine in part 1 will not receive any vaccine group 2: volunteers who received a first dose of cd40.rbdv vaccine (adjuvanted or not) in part 1 but randomized (1:1) to receive no further dose of vaccine in part 2. group 3: volunteers who received a first dose of cd40.rbdv vaccine (adjuvanted or not) in part 1 and randomized (1:1) to receive an additional dose of cd40.rbdv vaccine (adjuvanted or not)

Eligibility criteria:
inclusion criteria: * healthy volunteers age ≥18 and \<85 * able to understand and comply with planned study procedures and sign an informed consent before performance of any study-related screening procedures * who has received a primary series of vaccination and ≥ 1 booster(s) of covid-19 mrna vaccination(s) with the last boost at least 6 months prior to the inclusion in the study * subjects has adequate organ functions, evidenced by normal alt, ast, and alkaline phosphatase * normal haematology lab values * negative virology assessment * normal urine testing * volunteers must meet the eligibility criteria in the approved package labelling of the active comparator * for women of childbearing potential: use of an effective contraceptive method and negative pregnancy test. for male participants, use of an effective method of contraception with their partner exclusion criteria: * acute febrile infection within the previous 72 hours and/or presenting symptoms suggestive of covid-19 or sars cov 2 infection within the previous 28 days * immunosuppressive medications received within last three months before first imp administration or within 6 months for chemotherapies * immunoglobulins within 90 days before first imp administration * blood products within 120 days before first imp administration * any medical condition, such as cancer, that might impair the immune response * use of any experimental therapy * intent to participate in another study of an investigational research agent within 4 weeks prior to the enrolment visit or until the end of the study * currently pregnant or breastfeeding * history of severe adverse events following vaccine administration * any bleeding disorder considered as a contraindication to an intramuscular injection * a condition that requires active medical intervention or monitoring to avert grave danger to asthma other than mild, well-controlled asthma. * hypertension * bmi ≥ 40 kg/m2; ≤ 18 kg/m2; or bmi ≥ 35 kg/m2 with 2 or more of the following: age \> 45, current smoker, known hyperlipidemia, blood pressure is defined as consistently ≥ 140 mm hg systolic and ≥ 90 mm hg diastolic * malignancy * asplenia * seizure disorder * history of hereditary angioedema acquired angioedema, or idiopathic angioedema * history of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including arrhythmia requiring medication, treatment, or clinical follow-up * history of autoimmune disease * any medical, occupational, or other condition that, in the judgment of the investigator, would interfere with or serve as a contraindication to protocol adherence * psychiatric condition that precludes compliance with the protocol. * live attenuated vaccines received within 30 days before first imp administration or scheduled within 28 days after one of the last injection according to the protocol * vaccines that are not live attenuated vaccines and were received within 21 days prior to first imp administration * allergy treatment with antigen injections within 30 days before first imp administration and until the end of the study

Keywords: vaccine covid-19