The SOLVE-01 trial is a study evaluating four SARS-CoV-2 vaccines as booster injections: two experimental vaccines (CD40.RBDv and CD40.Pan.CoV, both combined with the Hiltonol® adjuvant) and two authorised vaccines (Comirnaty® and NuvaxovidTM). This trial is designed for healthy adults aged 18 to 65 at the time of signing the informed consent form. The main objectives of this trial are: * to evaluate the safety of the two experimental vaccines, * to determine the antibody response induced by the vaccines and its durability. Participants will: * Receive one injection of vaccine and two intradermal skin tests * Come to the hospital 10 visits for medical exams and blood and saliva sample collection * Keep a diary of their symptoms and the treatments taken
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
used at the dose of 1.0 mg subcutaneously Poly-ICLC adjuvant (Hiltonol) used at a dose of 1.0 mg and will be mixed with CD40.RBDv vaccine just prior to subcutaneous injection at day 0.
used at the dose of 1.0 mg subcutaneously Poly-ICLC adjuvant (Hiltonol) used at a dose of 1.0 mg and will be mixed with CD40.Pan.CoV vaccine just prior to subcutaneous injection at day 0.
administered intramuscularly at day 0. The version of the Comirnaty® vaccine and the dose will be the one adapted to the variant circulating at the start of trial and authorised by EMA.
administered intramuscularly at day 0. The version of the Nuvaxovid™ vaccine and the dose will be the one commercialised at the start of trial and authorised by EMA.
Hôpital Henri Mondor
Créteil, France
RECRUITINGCIC 1417 - Hôpital Cochin
Paris, France
RECRUITINGCentre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Switzerland
RECRUITINGSafety_Proportion of participants without any grade 3 or 4 adverse event
Proportion of participants without any grade 3 or 4 solicited local/systemic or unsolicited AEs between Day 0 and Week 4 and considered to be related or possibly related to IMP administration
Time frame: Between Day 0 and Week 4
Immunogenicity_Geometric mean titers of neutralizing antibodies
Geometric mean titers of neutralizing antibodies against the original strain D614G and the relevant circulating variants measured at Week 4 and Week 48
Time frame: At Week 4 and Week 48
Safety_Number of Solicited local and systemic Adverse Reactions
overall; by grade
Time frame: up to Day 7 (7 days post vaccination) for local ARs and Week 2 (14 days post vaccination) for systemic ARs
Safety_Number of Unsolicited adverse events
overall; by grade; by relationship to the vaccine
Time frame: from Day 0 to end of trial
Safety_Number of Serious Adverse Events
overall; by grade; by relationship to the vaccine
Time frame: from Day 0 to end of the trial
Immunogenicity_humoral immune response (IgG binding)
Geometric mean titers of IgG binding/neutralizing antibodies titers against the original strain D614G and the relevant circulating variants
Time frame: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48
Immunogenicity_humoral immune response (IgG binding)
Responders as defined by an increase of neutralizing antibodies at least 4-fold
Time frame: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48
Immunogenicity_persistence of immune imprinting
Estimation of the IgG ratio VOC/Wuhan
Time frame: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48
Immunogenicity_humoral immune response (neutralizing antibody titers)
Geometric mean titers of neutralizing antibodies titers against the original strain D614G and the relevant strain circulating
Time frame: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48
Immunogenicity_humoral immune response (neutralizing antibody titers)
Responders as defined by an increase of neutralizing antibodies at least 4-fold
Time frame: at Day 0 (before vaccination), Day 7, Week 2, Week 4, Week 12, Week 24, Week 36 and Week 48
Immunogenicity_specific antibody responses
Estimation and modelling of the slopes of antibody (binding and neutralizing) taking account all Ig measures collected during the follow-up
Time frame: between Day 0 and Week 48
Immunogenicity_T-cell immunogenicity (polyfunctional cross reactive specific T-cells)
Cytokine expression patterns of T-cells measured by intracellular cytokine staining assay
Time frame: at Day 0 (before vaccination), Week 4, Week 12, Week 24, Week 36 and Week 48
Immunogenicity_T-cell immunogenicity (polyfunctional cross reactive specific T-cells)
Magnitude (percentage) of cells producing at least one cytokine
Time frame: at Day 0 (before vaccination), Week 4, Week 12, Week 24, Week 36 and Week 48
Immunogenicity_durability of T-cell immune responses (polyfunctional cross reactive specific T-cells)
Frequency of specific T-cell responses
Time frame: at Day 0 (before vaccination), Week 24 and Week 48
Immunogenicity_correlation between the magnitude of CD4+ specific T-cell responses and levels of IgG specific responses
Frequency of specific CD4+ T-cell producing cytokines (ICS) and titers of binding and neutralizing antibody levels at the peak of IgG responses
Time frame: at Day 0 (before vaccination), Week 4, Week 12, Week 24, Week 36 and Week 48
Immunogenicity_repertoire of blood SARS-CoV-2 specific B-cells
Frequency and breadth of the SARS-CoV-2 specific memory B-cell responses
Time frame: at Day 0 (before vaccination), Day 7, Week 12, Week 24, and Week 48
Immunogenicity_innate immune responses
Correlation of innate immune responses to the different vaccines with the induction of long-lasting T- and B-cells adaptive immunity. Evaluation of the pre-vaccine innate immune profile and how it correlates with the magnitude, breadth, and durability of the adaptive immune response. Combined analysis of the mass cytometry cell specific analysis of the innate immune profile with the gene expression analysis performed at the same time points.
Time frame: at Day 0 (before vaccination), Day 1, Day 7, Week 2, Week 4 and Week 12
Immunogenicity_Gene expression
Changes in gene expression at each time point. Comparison of changes in gene abundance at each time point versus baseline
Time frame: at Day 0 (before vaccination), Day 1, Day 7, Week 2, and Week 4
Immunogenicity_T lymphocyte response
Analysis of TCR profiles in the blood and on sorted specific T-cells by single-cell approach
Time frame: at Day 0 (before vaccination), Day 1, Day 7, Week 2, and Week 4
Immunogenicity_mucosal immunity
Comparative analysis of anti-SARS-CoV-2 IgG and IgA mucosal antibody levels
Time frame: at Day 0, Day 7, Week 4, Week 12, and Week 24
Immunogenicity_T-cell memory responses
Size (area) of the intradermal skin test reaction
Time frame: at Week 24 and Week 48
Immunogenicity_serum levels of cytokine, chemokine and growth factor
Correlation of the serum cytokine, chemokine and growth factor profile with the magnitude, breadth and durability of the adaptive immune response induced by the different vaccines. These data will be combined with innate immune and gene expression analysis to provide a comprehensive systems biology evaluation of the factors contributing to an effective vaccine candidate.
Time frame: at Day 0, Day 1, Day 7, Week 2, Week 4 and Week 12
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