Evaluation of the Immunogenicity and Safety of COVID-19 Vaccines (Ad26.COV2.S and NVX-CoV2373)

Study Overview
=================
Brief Summary
-----------------
Phase II, non-randomized, open-label, comparative, national, multicenter trial in Mali, aimed to assess the humoral vaccine immune response induced by Ad26.COV2.S and NVX-CoV2373 vaccines in 400 adults (200 participants for each vaccine), one month after receiving the complete vaccination schedule of SARS-CoV-2 vaccine.

Detailed Description
-----------------
The main objective of this phase II trial is to evaluate the humoral immune response induced by the Ad26.COV2.S or NVX-CoV2373 vaccines in adults one month after complete vaccination regimen against SARS-CoV-2, compared younger (up to 45 years old) and elderly (55+ years old) populations. 400 participants will be included, 200 participants for each vacine. The age categories are 18 - 45 years, 55 - 64 years and 65+ years. The number of participants per age group will be distributed as follows 1:1:0,5. There will be no comparison between population on different vaccines. Ad26.COV2 vaccine (200 participants) 18-45 years old, 80 participants 55-64 years old, 80 participants 65 years old or older, 40 participants NVX-CoV2373 vaccine (200 participants) 18-45 years old, 80 participants 55-64 years old, 80 participants 65 years old or older, 40 participants Participants in Ad26.COV2 arm receive intramuscularly as a single dose of 0.5mL. Participants in NVX-CoV2373 arm receive 2 doses intramuscularly, the second dose 21 days apart, 0.5mL each. Humoral vaccine immune responses, induced by Ad26.COV2.S and NVX-CoV2373 vaccines, will be measured by ELISA at D0, M1, M2, M6, M12 and M24.

Official Title
-----------------
Phase II Trial Evaluating the Immunogenicity and Safety of Ad26.COV2.S and NVX-CoV2373 Vaccines in Adult Participants in Mali

Conditions
-----------------
COVID-19, Vaccine Reaction, SARS CoV 2 Infection, Vaccine Adverse Reaction

Intervention / Treatment
-----------------
* Biological: Ad26.COV2.S
* Biological: NVX-CoV2373


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age between 18 and 45 years old or 55 years and older Be eligible to receive one of the study vaccines as part of the trial Understand and agree to comply with study procedures (visits, telephone calls) Agree not to participate in any other vaccine study during the time of the study Give written informed consent prior to any examination performed as part of the trial Exclusion Criteria: Positive SARS-CoV-2 antigenic test Positive SARS-CoV-2 polymerase chain reaction (PCR) results less than 48 hours old History of infection by SARS-CoV-2 confirmed by antigenic test or PCR within 3 months prior to inclusion Symptoms compatible with infection to SARS-CoV-2: sick or febrile participants (body temperature ≥ 38.0°C) Pregnant or breastfeeding woman Known chronic disease impacting the participant's immune response (uncured cancer, human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection) Anti-coagulant treatment Immunosuppressive treatment Contraindication to the proposed vaccine (according to RCP) Previously received at least one injection of a SARS-CoV-2 vaccine Patient having received immunoglobulin or another blood product within 3 months prior to inclusion A history of serious adverse vaccine reactions (anaphylaxis and associated symptoms such as rash, breathing difficulties, laryngeal edema, or a history of allergic reaction that may be exacerbated by a component of the SARS-CoV-2 vaccine) Any condition that, in the opinion of the investigator, may adversely affect the well-being of the participant and interfere with the purpose of the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two trials using two different vaccines will be conducted in parallel at the same study sites, however, the 2 arms will not be compared nor interfere to each other.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ad26.COV2.S<br>Single dose (0.5mL) of SARS-CoV-2 vaccine Ad26.COV2.S. | Biological: Ad26.COV2.S<br>* Recombinant vaccine, contains Adenovirus type 26 encoding the SARS-CoV-2 spike glycoprotein<br>* Other names: Johnson&Johnson;|
| Experimental: NVX-CoV2373<br>Two doses (0.5mL) of SARS-CoV-2 vaccine NVX-CoV2373, the second dose administered 21 (+/-2 days) days after the first dose. | Biological: NVX-CoV2373<br>* Recombinant, adjuvanted vaccine, contains SARS-CoV-2 spike protein adjuvanted with Matrix-M<br>* Other names: Nuvaxovid;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-SARS-CoV-2 Spike immunoglobulin G (IgG) level | Anti-SARS-CoV-2 Spike IgG level is measured using ELISA test | One month after complete vaccination schema | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-SARS-CoV-2 Spike IgG level | Anti-SARS-CoV-2 Spike IgG level is measured using ELISA test | At inclusion (Day 0) and then 1, 2, 6, 12, and 24 months after inclusion | 
| Anti-SARS-CoV-2 immunoglobulin M (IgM) level | Anti-SARS-CoV-2 IgM level is measured using ELISA test | At inclusion (Day 0) and then 1, 2, 6, 12, and 24 months after inclusion | 
| Neutralizing antibody level for SARS-CoV-2 | Neutralizing antibody levels specific for SARS-CoV-2 and its variants (conventional in vitro neutralization and pseudo-neutralization assays) | Inclusion (Day 0) and then 1, 2, 6, 12, and 24 months after inclusion | 
| Fluorospot tests (type 1,2, and 17 helper T cell (TH1, TH2, TH17), Cytotoxicity) | Fluorospot tests (TH1, TH2, TH17, Cytotoxicity) Phenotyping of antigen-specific T cells by mass cytometry at Day 0 and Month 6 selected from the results of the Fluorospot test. | Inclusion (Day 0) and then 2 and 6 months after inclusion | 
| Mucosal SARS-CoV-2 specific antibody levels | Mucosal SARS-CoV-2 specific antibody levels by measuring IgA, IgM and IgG in saliva using specific ELISAs | Inclusion (Day 0) and then 1, 2, 6, 12, and 24 months after inclusion | 
| Determination of Epitope profile | Determination of epitope profile | Day 0 and Month 2 | 
| B cell response to vaccine | Determination of repertoire of B cells (stereotype clonotype) | Day 0, Month 2, Month 6 | 
| Measurement of ultrasensitive immunoglobulin A (IgA) and mucosal IgA and IgM functionality | Measurement of ultrasensitive IgA in saliva by Photoring assay Measurement of mucosal IgA and IgM functionality by SARS-CoV-2 mucosal IgA- and IgM-specific antibody-dependent cell-mediated cytotoxicity (ADCC) test | Day 0 and then 1, 2, 6, 12, and 24 months after inclusion | 
| Rate of adverse events | Rate of adverse events of any grade attributable to the vaccine or vaccination occurring between Month 1 and Month 24 | Between month 1 and month 24 after inclusion | 
| SARS-CoV-2 infection | Occurrence of confirmed COVID-19 cases during participant follow-up | Date of inclusion until 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ad26.COV2.S, NVX-CoV2373