FluMos-v2 Vaccine for Flu

Overseen By VRC Clinic

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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 You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 13

Duration: 16 weeks

45 Participants Needed

Trial Summary

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}

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 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.

Research Team

Lasonji A Holman, C.R.N.P.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

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.

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
• VRC-FLUMOS0116-00-VP

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

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

A vaccinia-based influenza vaccine that targets conserved internal proteins successfully broadened T-cell immunity in mice, allowing for a stronger immune response against various influenza strains.

This vaccine provided significant protection against both closely related and more distant influenza strains, demonstrating its potential as a broadly protective option against unpredictable influenza pandemics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection. Kwon, JS., Yoon, J., Kim, YJ., et al.[2014]

The FLU-v vaccine candidate, which targets cellular immunity, was found to be safe and well tolerated in a phase Ib trial involving 32 male participants, with significant increases in FLU-v-specific immune responses observed 19 days post-vaccination.

Participants who received FLU-v showed reduced viral loads and symptom scores after being challenged with the influenza virus, indicating that enhanced cellular immunity correlates with better clinical outcomes.

NCBI (Pubmed)

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. Pleguezuelos, O., Robinson, S., Fernández, A., et al.[2018]

The VN1203delNS1 vaccine candidate, developed from the H5N1 strain A/Vietnam/1203/04, has shown promising safety and immunogenicity in both mouse and macaque models.

This vaccine works by deleting the NS1 protein, which normally helps the virus evade the immune system, suggesting it could provide effective cross-protection against various H5N1 virus clades.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preclinical studies of live intranasal H5N1 influenza vaccine with the deleted HS1 gene]. Romanovskaia-Roman'ko, EA., Ferko, B., Vyshemirskiĭ, OI., et al.[2019]

The study evaluated a seasonal trivalent virosomal vaccine adjuvated with Matrix-M, showing that it provided some protection against avian influenza H5 and H7 strains in mice and ferrets, although the protection was not complete.

In ferrets challenged with H5N1, the vaccine reduced viral loads and lung pathology, suggesting that this adjuvated vaccine could serve as a temporary measure to lessen the impact of a potential pandemic outbreak.

NCBI (Pubmed)

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. Cox, F., Roos, A., Hafkemeijer, N., et al.[2018]

The MVA-NP+M1 influenza vaccine significantly boosted T-cell responses in healthy adults, demonstrating its immunogenicity after a single dose, which is crucial for effective protection against influenza.

In a controlled challenge study, vaccinees experienced milder symptoms and shorter virus shedding duration compared to controls, indicating the vaccine's potential efficacy in reducing influenza severity and transmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans. Lillie, PJ., Berthoud, TK., Powell, TJ., et al.[2022]

References

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

Vaccinia-based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection. [2014]

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]

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

[Preclinical studies of live intranasal H5N1 influenza vaccine with the deleted HS1 gene]. [2019]

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]

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]