Evaluating the Dose, Safety, Tolerability, and Immunogenicity of Mosaic Hexavalent Influenza Vaccine VRCFLUMOS0116-00-VP (FluMos-v2) With and Without ALFQ Adjuvant in Healthy Adults

NCT06863142 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002293002293-I
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Vaccines help the body learn to fight infections. Some vaccines are combined with adjuvants, which are added substances that make vaccines work better. FluMos-v2 is an experimental flu vaccine; ALFQ is an experimental adjuvant. Objective: To test FluMos-v2, with and without the ALFQ adjuvant, in healthy adults. Eligibility: Healthy adults aged 18 to 50 years. They must have received at least one flu vaccine from the 2020-21 season through the 2024-25 flu season. They must also agree not to receive the licensed 2025-26 flu vaccine. Design: Participants will have 12 clinic visits over 15 months. Participants will be screened. They will have a physical exam and blood tests. On 2 visits, about 4 months apart, participants will receive a vaccination. The shots will be given into the muscle of the upper arm. They will get a follow-up call the day after each shot. They will keep a daily diary for 7 days; they will record their temperature and any other symptoms they feel after each shot. All clinic visits will include collection of blood, saliva, and nasal secretions. If participants develop flu symptoms (such as fever, runny nose, sore throat), they will be asked to come to the clinic. About 2 weeks after each vaccination, participants may opt to undergo apheresis: Blood will be taken from the body through a needle inserted into one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be returned to the body through a needle in the other arm.

Conditions

Influenza Prevention; Seasonal Influenza

Keywords

Dose - Escalation; Immune Response; Viral Infection; Respiratory Illness; Experimental Vaccine; Experimental Adjuvant; Influenza Vaccine

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability of the FluMos-v2 (180 mcg) vaccine with ALFQ adjuvant administered to healthy adults at Day 0 and Week 16.

  To evaluate the safety and tolerability of a 2 dose regimen with ALFQ adjuvant.

  Through 68 weeks following the first vaccine administration, including through the 2025-2026 influenza season.

• Safety and tolerability of the FluMos-v2 (60 mcg) vaccine with ALFQ adjuvant administered to healthy adults at Day 0 and Week 16.

  To evaluate the safety and tolerability of a 2 dose regimen with ALFQ adjuvant.

  Through 68 weeks following the first vaccine administration, including through the 2025-2026 influenza season.

• Safety and tolerability of the FluMos-v2 (180 mcg) vaccine administered alone to healthy adults at Day 0 and Week 16.

  To evaluate the safety and tolerability of a 2 dose regimen

  Through 68 weeks following the first vaccine administration, including through the 2025-2026 influenza season

Secondary Outcomes (2)

• Antibody responses to the FluMos-v2 (180 mcg) vaccine administered alone as a 2 dose regimen to healthy adults at 2 weeks after each injection at Week 2 and Week 18.

  Through 18 weeks following the first vaccine administration, including through the 2025-2026 influenza season.

• Antibody responses to the FluMos-v2 (180 mcg) with ALFQ adjuvant vaccine administered as a 2 dose regimen to healthy adults at 2 weeks after each injection at Week 2 and Week 18.

  Through 18 weeks following the first vaccine administration, including through the 2025-2026 influenza season.

Study Arms (4)

Group 1

EXPERIMENTAL

180 mcg of FluMos-v2 Day 0 and Week 16

Biological: VRC-FLUMOS0116-00-VP

Group 2

EXPERIMENTAL

60 mcg of FluMos-v2 + 0.5 ml of ALFQ Day 0 and Week 16

Biological: VRC-FLUMOS0116-00-VP; Other: ALFQ

Group 3A

EXPERIMENTAL

180 mcg of FluMos-v2 + 0.5 ml of ALFQ Day 0 and Week 16

Biological: VRC-FLUMOS0116-00-VP; Other: ALFQ

Group 3B

EXPERIMENTAL

180 mcg of FluMos-v2 + 0.5 ml of ALFQ Day 0 and Week 16

Biological: VRC-FLUMOS0116-00-VP; Other: ALFQ

Interventions

VRC-FLUMOS0116-00-VP BIOLOGICAL

The VRC-FLUMOS0116-00-VP (FluMos-v2) vaccine is composed of de novo engineered pentamer assembled with de novo engineered trimeric domains to an icosahedral core, projecting 20 HA ectodomain trimers from influenza strains: Influenza A (H1-H3) and Influenza B (Victoria lineage and Yamagata lineage)

Group 1; Group 2; Group 3A; Group 3B

ALFQ OTHER

The ALFQ adjuvant is a sterile suspension that contains monophosphoryl 3-deacyl Lipid A \[3D-PHAD(R)\] and QS-21

Group 2; Group 3A; Group 3B

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• A participant must meet all of the following criteria:
• Healthy adults between the ages of 18-50 years, inclusive

You may not qualify if:

• Received at least one licensed influenza vaccine from the 2020-2021 influenza season through the 2024-2025 influenza season
• Able and willing to complete the informed consent process
• Available for clinic visits for 68 weeks after enrollment, including through the 2025-2026 influenza season
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
• Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) \<= 35 within the 56 days before enrollment
• Agrees to not receive the 2025-2026 licensed influenza vaccination during study participation due to potential confounding of study results
• Willing to have blood and mucosal samples collected, stored indefinitely, and used for research purposes
• Laboratory Criteria within 56 days before enrollment
• White blood cells (WBC) and differential within institutional normal range or accompanied by approval of the site Principal Investigator (PI) or designee
• Total lymphocyte count \>= 800 cells/microL
• Platelets = 125,000 - 400,000 cells/microL
• Hemoglobin within institutional normal range or accompanied by approval of the PI or designee
• Alanine aminotransferase (ALT) \<= 1.25 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) \<= 1.25 x institutional ULN
• Alkaline phosphatase (ALP) \< 1.1 x institutional ULN

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Widge AT, Hofstetter AR, Houser KV, Awan SF, Chen GL, Burgos Florez MC, Berkowitz NM, Mendoza F, Hendel CS, Holman LA, Gordon IJ, Apte P, Liang CJ, Gaudinski MR, Coates EE, Strom L, Wycuff D, Vazquez S, Stein JA, Gall JG, Adams WC, Carlton K, Gillespie RA, Creanga A, Crank MC, Andrews SF, Castro M, Serebryannyy LA, Narpala SR, Hatcher C, Lin BC, O'Connell S, Freyn AW, Rosado VC, Nachbagauer R, Palese P, Kanekiyo M, McDermott AB, Koup RA, Dropulic LK, Graham BS, Mascola JR, Ledgerwood JE; VRC 321 study team. An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults. Sci Transl Med. 2023 Apr 19;15(692):eade4790. doi: 10.1126/scitranslmed.ade4790. Epub 2023 Apr 19.

  PMID: 37075129 BACKGROUND

• Ober Shepherd BL, Scott PT, Hutter JN, Lee C, McCauley MD, Guzman I, Bryant C, McGuire S, Kennedy J, Chen WH, Hajduczki A, Mdluli T, Valencia-Ruiz A, Amare MF, Matyas GR, Rao M, Rolland M, Mascola JR, De Rosa SC, McElrath MJ, Montefiori DC, Serebryannyy L, McDermott AB, Peel SA, Collins ND, Joyce MG, Robb ML, Michael NL, Vasan S, Modjarrad K; EID-030 Study Group. SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial. Lancet Microbe. 2024 Jun;5(6):e581-e593. doi: 10.1016/S2666-5247(23)00410-X. Epub 2024 May 15.

  PMID: 38761816 BACKGROUND

• Boyoglu-Barnum S, Ellis D, Gillespie RA, Hutchinson GB, Park YJ, Moin SM, Acton OJ, Ravichandran R, Murphy M, Pettie D, Matheson N, Carter L, Creanga A, Watson MJ, Kephart S, Ataca S, Vaile JR, Ueda G, Crank MC, Stewart L, Lee KK, Guttman M, Baker D, Mascola JR, Veesler D, Graham BS, King NP, Kanekiyo M. Quadrivalent influenza nanoparticle vaccines induce broad protection. Nature. 2021 Apr;592(7855):623-628. doi: 10.1038/s41586-021-03365-x. Epub 2021 Mar 24.

  PMID: 33762730 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Virus Diseases; Influenza, Human

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Infections; Orthomyxoviridae Infections; RNA Virus Infections; Respiratory Tract Diseases

Study Officials

• Lasonji A Holman, C.R.N.P.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

VRC Clinic

CONTACT

(301) 451-8715; vaccines@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: March 7, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02-19

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)