Design:
This is a phase I, open-label, dose escalation study to evaluate the safety, tolerability, and immunogenicity of the stem quadrivalent influenza vaccine VRC-FLUMOS0122-00-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. The primary objective is to evaluate the safety and tolerability of the investigational vaccine with and without ALFQ adjuvant in healthy adults. Secondary objectives are related to the immunogenicity of the investigational vaccine with and without ALFQ adjuvant.
Study Products:
The investigational vaccine, SteMos1, was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID). The adjuvant, Army Liposome Formulation containing QS-21 (ALFQ), was developed and provided by the Walter Reed Army Institute of Research (WRAIR).
The SteMos1 vaccine includes stabilized HA stems from the following 4 influenza strains:
Influenza A:
Group 1:
H2: A/Singapore/1/1957
H5: A/lndonesia/5/2005
Group 2:
H7: A/Anhui/1/2013
H10: A/Jiangxi-Donghu/346/2013
Participants:
Healthy adults 18-50 years of age, inclusive, will be enrolled
Study Plan:
There will be multiple interim safety reviews in this trial. The first review will assess the safety data for Group 1 (60 mcg of SteMos1 alone). Enrollment for Group 1 will be limited to one participant per day for the first three participants. After the third participant's two-week post-vaccination visit, a safety review will determine whether to continue enrollment at the same dose level in Group 1 and to proceed with enrollment of the next dose level, Group 2 (180 mcg of SteMos1 alone), and Group 3 (60 mcg of SteMos1 with ALFQ adjuvant). Group 2 and Group 3 will also enroll one participant per day for the first three participants in each group. Following the two-week post-vaccination visit of the third participant in each group, a safety review will determine whether to continue enrollment at the same dose level in Group 2 and Group 3 and to proceed to the next dose level, Group 4 (180 mcg of SteMos1 with ALFQ adjuvant). At this stage, these interim safety reviews for Group 2 and Group 3 can be conducted simultaneously or at different times, depending on which group first completes enrollment of the initial three participants.
Group 4 will enroll one participant per day for the first three participants. After the two-week post-vaccination visit of the third participant, a final safety review will determine whether to continue enrollment at the same dose level in Group 4. The study will not enroll any participants in Group 5 until available interim safety data from Group 3 and Group 4 are evaluated to select the dose for Group 5.
Once all groups are open, participants will be enrolled at the discretion of the Principal Investigator (PI) to balance enrollments in each group. If a current participant is discontinued from the protocol, a new participant may be enrolled at the discretion of the PI to collect required safety or immunogenicity data.
Solicited reactogenicity will be evaluated using a 7-day diary card. Assessment of vaccine safety will include clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study.
Study Duration:
Participants will be followed for safety for a total time of 68 weeks, including through the 2025-2026 influenza season. This safety follow-up includes 52 weeks after the second dose of vaccine.
