Quadrivalent Influenza HA Stem Vaccine VRC-FLUMOS0122-00-VP (SteMos1) With and Without ALFQ Adjuvant in Healthy Adults

Description

Design:

This is a phase I, open-label, dose escalation study to evaluate the safety, tolerability, and immunogenicity of the stem quadrivalent influenza vaccine VRCFLUMOS0122- 00-VP (SteMos1) with and without Army Liposome Formulation containing saponin QS-21 (ALFQ) adjuvant. The hypotheses are that the SteMos1 vaccine is safe and tolerable when administered alone or with ALFQ adjuvant, that this vaccine elicits vaccine specific immune responses, and that addition of the ALFQ adjuvant increases the magnitude and breadth of the elicited immune responses.

Objectives:

Primary Objective:

* To evaluate the safety and tolerability of 60 mcg of SteMos1 without adjuvant administered IM via needle and syringe as a 2-dose regimen to healthy adults
* To evaluate the safety and tolerability of 180 mcg of SteMos1 without adjuvant administered IM via needle and syringe as a 2-dose regimen to healthy adults
* To evaluate the safety and tolerability of 60 mcg of SteMos1 plus ALFQ administered IM via needle and syringe as a 2-dose regimen to healthy adults
* To evaluate the safety and tolerability of 180 mcg of SteMos1 plus ALFQ administered IM via needle and syringe as a 2-dose regimen to healthy adults

Secondary Objective:

* To evaluate antibody responses, at two weeks after each injection, to 60 mcg of SteMos1 without adjuvant administered IM via needle and syringe as a 2-dose regimen.
* To evaluate antibody responses, at two weeks after each injection, to 180 mcg of SteMos1 without adjuvant administered IM via needle and syringe as a 2-dose regimen
* To evaluate antibody responses, at two weeks after each injection, to 60 mcg of SteMos1 plus ALFQ administered IM via needle and syringe as a 2-dose regimen
* To evaluate antibody responses, at two weeks after each injection, to 180 mcg of SteMos1 plus ALFQ administered IM via needle and syringe as a 2-dose regimen

Exploratory Objectives:

– To evaluate the specificity and functionality of the immune response induced by SteMos1vaccine with and without ALFQ adjuvant at various timepoints throughout the study

Endpoints:

Primary Endpoints:

* Frequency and severity of solicited local reactogenicity symptoms reported for 7 days following each injection, through resolution of symptoms
* Frequency and severity of solicited systemic reactogenicity symptoms reported for 7 days following each injection, through the resolution of symptoms.
* Frequency and grade of any unsolicited AEs, including abnormal safety laboratory measures, during the 28-day follow-up period post each product administration.
* Frequency and grade of unsolicited AEs assessed as related to the product during the 28-day follow-up period after each product administration,
* Frequency of adverse events leading to participant s withdrawal at any time throughout the study
* Frequency of SAEs, AESI, MAAEs and new chronic medical conditions that require ongoing medical management at any time throughout the study

Secondary Endpoints:

– Binding antibody responses to VRCFLUMOS0122- 00-VP (SteMos1) with and without ALFQ adjuvant at Week 2 (Visit 04) after the first vaccination and at Week 18 (Visit 09), 2 weeks after the second vaccination

Exploratory Endpoints:

* Neutralizing antibody responses measured at various timepoints
* Frequency and magnitude of HA-specific B-cell responses at various time points throughout the study.
* Frequency and magnitude of antigen-specific T cell responses measured at various timepoints
* Binding antibody responses to the de novo engineered pentamer and trimer moieties (I53_dn5) measured at various time points throughout the study.
* Antigen-specific immune responses in mucosal compartments, measured using nasal and saliva samples at various time points throughout the study.
* Correlations between immunogenetic/immunological markers and vaccine response outcomes, including antibody titers and safety outcomes through whole genome sequencing (WGS).