FluMos-v2 Vaccine for Flu

Recruiting in Palo Alto (17 mi)

Overseen by Tejaswi S Dittakavi, D.O.

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Immunosuppressives, Cytotoxics, Anti-TB, others

Disqualifiers: Uncontrolled asthma, Diabetes, Hypertension, others

Stay on Your Current Meds

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 2023-24 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 are 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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive or cytotoxic medications, you may need to stop them at least 14 days before enrolling. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the FluMos-v2 Vaccine for Flu treatment?

The research shows that a similar vaccine, FLU-v, which also aims to boost cellular immunity, was effective in reducing flu symptoms and virus levels in a study. This suggests that treatments enhancing cellular immune responses, like FluMos-v2, could potentially be effective in managing flu symptoms. ^{1 2 3 4 5}

Eligibility Criteria

Healthy adults aged 18 to 50 who've had at least one flu shot between the 2020-21 and 2023-24 seasons. Participants must skip the licensed flu vaccine for the 2025-26 season. Ideal candidates are willing to attend multiple clinic visits, receive injections, and provide blood, saliva, and nasal samples.

Inclusion Criteria

In good general health without a history of conditions listed in the exclusion criteria

I have received a flu shot between the 2020-2021 and 2023-2024 seasons.

Available for clinic visits for 68 weeks after enrollment, including through the 2025-2026 influenza season

Exclusion Criteria

Breastfeeding or planning to become pregnant during the study

I plan to or must get the flu vaccine for 2025-2026 or received it for 2024-2025.

I have not received any inactivated vaccines in the last 2 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive the FluMos-v2 vaccine with or without ALFQ adjuvant at Day 0 and Week 16

16 weeks

2 visits (in-person), follow-up calls after each vaccination

Follow-up

Participants are monitored for safety and effectiveness after treatment, including through the 2025-2026 influenza season

52 weeks

10 visits (in-person)

Treatment Details

Interventions

• ALFQ (Adjuvant)
• VRC-FLUMOS0116-00-VP (Virus Therapy)

Trial Overview The trial is testing FluMos-v2, an experimental flu vaccine with or without ALFQ adjuvant. Over a period of about 15 months with approximately twelve clinic visits, participants will receive two shots into their upper arm muscles and may choose to undergo apheresis after vaccination.

Participant Groups

Group I: Group 3B Experimental Treatment 2 Interventions

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

Group II: Group 3A Experimental Treatment 2 Interventions

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

Group III: Group 2 Experimental Treatment 2 Interventions

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

Group IV: Group 1 Experimental Treatment 1 Intervention

180 mcg of FluMos-v2 Day 0 and Week 16

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID) Lead Sponsor

References

1. Germany pubmed.ncbi.nlm.nih.gov

Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection. [2014] Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell-based vaccine, but the narrow breadth of T-cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T-cell immunodominance hierarchy in humans in an experimental setting, influenza-primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN-γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T-cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD50 challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP366 epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV-NP + PA showed improved protection. Taken together, a vaccinia-based influenza vaccine expressing conserved internal proteins improved the breadth of influenza-specific T-cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains.

2. United States pubmed.ncbi.nlm.nih.gov

A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans. [2018] Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n = 16) or FLU-v (500 μg) and the adjuvant (n = 16), both in saline. Twenty-one days later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average ± the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold ± 0.2-fold and 1.6-fold ± 0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold ± 3.9-fold versus 1.3-fold ± 0.1-fold higher than the negative-control value [average ± SEM] for FLU-v versus the placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads. (This study has been registered at ClinicalTrials.gov under registration no. NCT01226758 and at hra.nhs.uk under EudraCT no. 2009-014716-35.).

3. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Preclinical studies of live intranasal H5N1 influenza vaccine with the deleted HS1 gene]. [2019] The paper gives the results of evaluating the efficiency of deINS1 pandemic H5N1 vaccine candidate VN1203delNS1 which was constructed by reverse genetics on the basis of influenza virus strain A/Vietnam/1203/04. The safety, immunogenicity and cross-protection of the vaccine strain against different H5N1 virus clades were demonstrated in mouse and macaque models. The results showed the possibility of designing a new-generation replication-deficient intranasal influenza vaccine, by applying an approach to deleting the NS1 pathogenicity factor, an antagonist of the interferon system.

4. United States pubmed.ncbi.nlm.nih.gov

Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge. [2018] There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

5. United States pubmed.ncbi.nlm.nih.gov

Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans. [2022] The novel influenza vaccine MVA-NP+M1 is designed to boost cross-reactive T-cell responses to internal antigens of the influenza A virus that are conserved across all subtypes, providing protection against both influenza disease and virus shedding against all influenza A viruses. Following a phase 1 clinical study that demonstrated vaccine safety and immunogenicity, a phase 2a vaccination and influenza challenge study has been conducted in healthy adult volunteers.