Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Mosaic Hexavalent Influenza Vaccine VRC-FLUMOS0116-00-VP (FluMos-v2) in Healthy Adults

Design:

This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of the mosaic hexavalent influenza vaccine VRC-FLUMOS0116-00-VP (FluMos-v2). For Part A, the hypotheses are that the FluMos-v2 vaccine is safe and tolerable and will elicit an immune response. For Part B, the hypothesis is that the vaccine will generate a germinal center (GC) response in a draining lymph node as determined by fine needle aspiration of a reactive ipsilateral axillary lymph node. The primary objective is to evaluate the safety and tolerability of the investigational vaccine in healthy adults. Secondary objectives are related to the immunogenicity of the investigational vaccine.

Study Products:

The investigational vaccine, FluMos-v2, was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID) and is composed of the following 6 influenza strains:

Influenza A:

• H1: A/Idaho/07/2018
• H2: A/Singapore/1/1957
• H3: A/Perth/1008/2019
• H3: A/Darwin/106/2020

Influenza B:

• B/Victoria lineage: B/Colorado/06/2017
• B/Yamagata lineage: B/Phuket/3073/2013

FluMos-v2 is supplied in a single-use vial at a target concentration of 180 mcg/mL and will be administered intramuscularly (IM) in the deltoid muscle via needle and syringe.

Subjects: Healthy adults between the ages of 18-50 years, inclusive, will be enrolled.

Study Plan:

In Part A, this study evaluates the safety, tolerability, and immunogenicity of FluMos-v2 in a dose escalation design.

In Part B, this study assesses GC and peripheral blood immune responses at different time points after vaccination with FluMos-v2.

For Part B: The protocol requires 2 vaccination visits, approximately 9-10 follow-up visits, 4 mandatory FNA visits and 1 optional FNA visit, and 10-12 telephone contacts. Safety phone calls occur one day after each vaccination, and 3 days after each FNA. Additional phone calls are related to scheduling the FNA procedures. Solicited reactogenicity is evaluated using a 7-day diary card. Assessment of vaccine safety includes clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study.

The study schema is as follows:

VRC 326 Vaccination Schema

Part A:

Group 1: Subjects:12, Day 0: 60 mcg, Week 16: 60 mcg, Product: FluMos-v2

Group 2: Subjects: 12, Day 0: 180 mcg, Week 16: 180 mcg, Product: FluMos-v2

Part B:

Group 3: Subjects: 6, Day 0: 180 mcg, Week 16: 180 mcg, Product: FluMos-v2

Total = 30 subjects (Enrollment up to 40 subjects is permitted if additional subjects are needed for safety or immunogenicity evaluations).

Study Duration:

Part A:

Subjects are evaluated for 40 weeks following first vaccine administration, including through the 2023-2024 influenza season.

Part B:

Subjects are evaluated for 40 weeks following the first vaccine administration, including through the 2024-2025 influenza season.

• INCLUSION CRITERIA:

A subject must meet all of the following criteria:

• Healthy adults between the ages of 18-50 years, inclusive
• Based on history and physical examination, in good general health and without history of any of the conditions listed in the exclusion criteria
• For Part A: Received at least one licensed influenza vaccine from 2018 through the 2022-2023 influenza season
• Able and willing to complete the informed consent process
• For Part A: Available for clinic visits for 40 weeks after enrollment, including through the 2023-2024 influenza season
• For Part B: Available for clinic visits for 40 weeks after enrollment, including through the 2024-2025 influenza season
• For Part B: Agrees to undergo four lymph node FNAs.
• 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
• For both Parts A and B: Agrees to not receive any licensed influenza vaccine during study participation due to potential confounding of study results
• Willing to have blood samples collected, stored indefinitely, and used for research purposes
• For Part B: Willing to have lymph node 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 the site Principal Investigator (PI) or designee approval
• Total lymphocyte count >= 800 cells/microliter
• Platelets = 125,000 - 500,000 cells/microliter
• Hemoglobin within institutional normal range or accompanied by the PI or designee approval
• 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
• Total bilirubin within institutional normal range or accompanied by the PI or designee approval
• Serum creatinine <= 1.1 x institutional ULN
• Negative for HIV infection by an FDA-approved method of detection

Criteria applicable to women of childbearing potential:

• Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on the day of enrollment
• Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the end of the study for sample collection.

Exclusion criteria

A participant will be excluded if one or more of the following conditions apply:

-Women breast-feeding or planning to become pregnant during the study

Participant has received any of the following substances:

• More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment
• Blood products within 16 weeks prior to enrollment
• Live attenuated vaccines within 4 weeks prior to enrollment
• Inactivated vaccines within 2 weeks prior to enrollment
• Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study (Note: SARS-CoV-2 vaccines licensed and/or approved by emergency use authorization are not exclusionary, but are subject to the criteria for timing of inactivated vaccines or mRNA vaccines)
• mRNA vaccines within 4 weeks prior to enrollment
• Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule
• Current anti-TB prophylaxis or therapy
• Receipt of investigational ferritin-based nanoparticle influenza vaccines, with the exception of participants previously enrolled in the VRC 316 study as follows: Group 2 (HA-F A/Sing prime, HA-F A/Sing boost), 3A (DNA A/Sing prime, HA-F A/Sing boost) or 4A (HA-F A/Sing prime, HA-F A/Sing boost).
• Receipt of the mosaic quadrivalent influenza vaccine VRC-FLUMOS0111-00-VP (FluMos-v1)
• Receipt of any licensed influenza vaccine within 6 months prior to enrollment.
• For Part A: Receipt of the 2023-2024 licensed influenza vaccine
• For Part B: Plan to or are required to receive the 2024-2025 licensed influenza vaccine
• For Part B: Receipt of any licensed seasonal influenza vaccine since the 2022-2023 influenza season; including the 2023-2024 influenza season through the 2024-2025 influenza season.

Subject has a history of any of the following clinically significant conditions:

• Serious reactions to vaccines that preclude receipt of the study vaccinations as determined by the investigator
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
• Asthma that is not well controlled
• Diabetes mellitus (type I or II), with the exception of gestational diabetes
• Thyroid disease that is not well controlled
• Idiopathic urticaria within the past year
• Autoimmune disease or immunodeficiency
• Hypertension that is not well controlled
• Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws
• Malignancy that is active or history of malignancy that is likely to recur during the period of the study
• Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years
• Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
• Guillain-Barre Syndrome
• Any medical, psychiatric, or social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a subject s ability to give informed consent, including but not limited to clinically significant forms of infectious diseases, drug or alcohol abuse, autoimmune diseases, psychiatric disorders, or heart disease.