Flu Vaccine for Influenza

Overseen By VRC Recruitment

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

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

Disqualifiers: Pregnancy, Asthma, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: 11

Duration: 16 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new flu vaccine, FluMos-v2, in healthy adults aged 18 to 50. The vaccine aims to protect against multiple flu strains by teaching the immune system to recognize and combat them. Participants will receive two shots and have follow-up visits over a period of time to monitor their health and immune response.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot receive any licensed flu vaccines during the study. If you are on certain treatments like systemic immunosuppressive medications, you may need to stop them before enrolling.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken certain vaccines or immunosuppressive medications recently. It's best to discuss your specific medications with the study team.

Is the FluMos-v2 vaccine generally safe for humans?

The safety data for various influenza vaccines, including Flublok Quadrivalent and Invivac, show that most adverse reactions are mild and not serious. However, some individuals may experience allergic reactions, and a few serious cases like Guillain-Barré syndrome have been reported. Overall, these vaccines are considered safe for most people. ^{1 2 3 4 5}

Is the FluMos-v2 flu vaccine generally safe for humans?

The safety data for various influenza vaccines, including Flublok Quadrivalent and others, show that most adverse events are non-serious, though some serious allergic reactions have been reported. These reactions may occur in people with a predisposition to allergies, and ongoing safety monitoring is important to understand the risks and benefits. ^{1 2 3 4 5}

How is the FluMos-v2 treatment different from other flu treatments?

The FluMos-v2 treatment is unique because it is designed to target both the spike protein of the SARS-CoV-2 Delta variant and the conserved influenza M2 domain, potentially offering protection against both COVID-19 and influenza simultaneously. ^{6 7 8 9 10}

How does the FluMos-v2 treatment differ from other flu treatments?

The FluMos-v2 treatment is unique because it is designed to target both the spike protein of the SARS-CoV-2 Delta variant and the conserved influenza M2 domain, potentially offering protection against both COVID-19 and influenza. This dual-target approach is different from traditional flu vaccines, which typically focus only on influenza strains. ^{6 7 8 9 10}

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

The research on a T-cell-based influenza vaccine, MVA-NP+M1, shows that boosting T-cell responses can provide protection against influenza, which suggests that similar approaches like FluMos-v2 might also be effective. Additionally, studies on bivalent vaccines that protect against both COVID-19 and influenza demonstrate that targeting conserved influenza proteins can effectively reduce viral loads, indicating potential effectiveness for FluMos-v2. ^{6 11 12 13 14}

What data supports the effectiveness of the treatment VRC-FLUMOS0116-00-VP (FluMos-v2) for influenza?

The study on a recombinant VSV-based bivalent vaccine shows that similar vaccine platforms can effectively protect against influenza by inducing strong immune responses and reducing viral loads in animal models. This suggests that the FluMos-v2 treatment may also be effective in providing protection against influenza. ^{6 11 12 13 14}

Who Is on the Research Team?

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

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Healthy adults aged 18-50 who've had a flu shot since 2018 can join this trial. They must be in good health, not pregnant or breastfeeding, and agree to avoid the standard flu vaccine for the study duration. People with poorly controlled thyroid disease, hypertension, autoimmune diseases, bleeding disorders, recent receipt of other vaccines or blood products are excluded.

Inclusion Criteria

Available for clinic visits for 40 weeks after enrollment, including through the 2023-2024 influenza season

I have received a flu shot at least once between 2018 and the 2022-2023 season.

Able and willing to complete the informed consent process

Exclusion Criteria

I have a bleeding disorder or often have issues with bleeding or bruising.

I have received specific experimental flu vaccines, except if I was in certain groups of the VRC 316 study.

I do not have a spleen or my spleen does not work properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the FluMos-v2 vaccine at Day 0 and Week 16

16 weeks

2 vaccination visits, 9-10 follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

9-10 follow-up visits, 4 mandatory FNA visits, 1 optional FNA visit

Extension

Participants are evaluated through the influenza season for additional safety and immunogenicity data

40 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VRC-FLUMOS0116-00-VP (FluMos-v2)

Trial Overview The trial is testing FluMos-v2, an experimental hexavalent influenza vaccine designed to protect against multiple strains of flu. Participants will receive two shots four months apart and have follow-up visits including temperature monitoring and blood draws over ten months.

How Is the Trial Designed?

Group I: Group 3 Experimental Treatment 1 Intervention

180 mcg of FluMos-v2 on Day 0 and Week16

Group II: Group 2 Experimental Treatment 1 Intervention

180 mcg of FluMos-v2 on Day 0 and Week16

Group III: Group 1 Experimental Treatment 1 Intervention

60 mcg of FluMos-v2 on 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+

Published Research Related to This Trial

The MVA-NP+M1 influenza vaccine was found to be safe and well-tolerated in a study involving 30 older adults (ages 50-85), with significant boosts in T cell responses observed after vaccination.

Unlike traditional seasonal influenza vaccines, MVA-NP+M1 generated similar immune responses in both older and younger individuals, suggesting it may effectively address the reduced immune response often seen in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. Antrobus, RD., Lillie, PJ., Berthoud, TK., et al.[2022]

ID Biomedical is developing a trivalent nasal influenza vaccine called FluINsure, which is designed to provide protection against multiple strains of the flu virus.

FluINsure is currently undergoing phase II clinical trials, indicating that it is in the testing phase to evaluate its safety and efficacy in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technology evaluation: FluINsure, ID Biomedical. Munoz, FM.[2019]

The A/H5N2 live attenuated influenza vaccine was found to be safe and well tolerated in a phase I clinical trial with 40 healthy volunteers, showing no increased rates of adverse events.

The vaccine demonstrated strong immunogenicity, with 96.6% of participants showing an immune response and significant seroconversion rates (37.9% and 48.3%) four weeks after the second dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical testing of pre-pandemic live attenuated A/H5N2 influenza candidate vaccine in adult volunteers: results from a placebo-controlled, randomized double-blind phase I study. Rudenko, L., Kiseleva, I., Stukova, M., et al.[2022]

The study developed three bivalent vaccine candidates using recombinant vesicular stomatitis virus (rVSV) that effectively target both SARS-CoV-2 Delta variant and influenza viruses, inducing strong immune responses in animal models.

Immunization with these rVSV-based vaccines provided significant protection against infections from the SARS-CoV-2 Delta variant and lethal H1N1 and H3N2 influenza viruses, demonstrating their potential efficacy in reducing respiratory viral loads.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Recombinant VSV-Based Bivalent Vaccine Effectively Protects against Both SARS-CoV-2 and Influenza A Virus Infection. Ao, Z., Ouyang, MJ., Olukitibi, TA., et al.[2022]

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]

In the first year after the high-dose trivalent inactivated influenza vaccine (TIV-HD) was licensed for adults aged 65 and older, 606 reports were made to the Vaccine Adverse Event Reporting System (VAERS), with only 8.2% involving serious events, indicating a generally favorable safety profile.

While no new serious safety concerns were identified, there was a notable increase in reported gastrointestinal events after TIV-HD compared to the standard dose vaccine, suggesting the need for further investigation into this potential association.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlicensure safety surveillance for high-dose trivalent inactivated influenza vaccine in the Vaccine Adverse Event Reporting System, 1 July 2010-31 December 2010. Moro, PL., Arana, J., Cano, M., et al.[2013]

The Integrated Vaccine Surveillance System (IVSS) successfully monitored adverse events following influenza vaccination in a pilot study with 605 adult participants, demonstrating that real-time data collection is feasible and effective.

Of the 545 participants who reported their experiences, 62% reported at least one adverse event, with 85% of these being mild symptoms, indicating a generally favorable safety profile for the 2008 seasonal influenza vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active surveillance for influenza vaccine adverse events: the integrated vaccine surveillance system. Newes-Adeyi, G., Greece, J., Bozeman, S., et al.[2013]

In a safety surveillance study of the Vaxigrip and Intanza 15 µg influenza vaccines during the 2016/17 season, 1.8% of Vaxigrip recipients and 2.1% of Intanza recipients reported suspected adverse reactions within 7 days, indicating a generally low incidence of side effects.

The safety profiles of both vaccines remained consistent with previous years, with no significant increase in adverse reactions, suggesting that both vaccines are safe for use in the population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report from enhanced safety surveillance of two influenza vaccines (Vaxigrip and Intanza 15 μg) in two European countries during influenza season 2016/17 and comparison with 2015/16 season. Chabanon, AL., Bricout, H., Ballandras, C., et al.[2019]

The recombinant hemagglutinin quadrivalent influenza vaccine (RIV4) was approved for use in individuals 18 years and older, showing a safety profile similar to standard-dose vaccines, with 95% of reported adverse events being non-serious.

Among the serious adverse events reported, there were 10 cases of Guillain-Barré syndrome, highlighting the importance of ongoing safety monitoring, although the overall incidence of serious reactions appears low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of quadrivalent recombinant influenza vaccine: Reports to the vaccine adverse event reporting system. Woo, EJ., Moro, PL.[2021]

The virosomal influenza vaccine (Invivac) demonstrated high efficacy, with 76 to 99% of subjects with low pre-vaccination antibody levels achieving protective immunity after vaccination, based on data from 14 clinical studies involving 2865 participants.

The vaccine was found to be safe, with acceptable rates of mild and transient local and systemic reactions, making it suitable for both healthy adults and those with chronic illnesses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virosomal influenza vaccine: a safe and effective influenza vaccine with high efficacy in elderly and subjects with low pre-vaccination antibody titers. de Bruijn, IA., Nauta, J., Gerez, L., et al.[2005]

Vero cell culture-derived whole-virus influenza vaccines have shown broad cross-clade protection against pandemic potential viruses, demonstrating safety and immunogenicity in over 10,000 individuals across various age groups and risk categories.

These vaccines can be produced at low antigen doses without needing adjuvants and are already licensed for both prepandemic and pandemic use, with ongoing research into next-generation vaccine development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vero cell culture-derived pandemic influenza vaccines: preclinical and clinical development. Barrett, PN., Portsmouth, D., Ehrlich, HJ.[2013]

The study developed novel influenza vaccine candidates using Ebola glycoprotein technology, which effectively targeted dendritic cells and induced strong antibody responses in mice against influenza proteins.

Vaccination with these candidates (rVSV-EΔM-tM2e and rVSV-EΔM-HM2e) provided significant protection to mice against influenza H1N1 and H3N2, suggesting their potential as universal vaccine options for various influenza strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and characterization of influenza M2 ectodomain and/or hemagglutinin stalk-based dendritic cell-targeting vaccines. Olukitibi, TA., Ao, Z., Azizi, H., et al.[2023]

The new Russian influenza vaccine 'Grifor' is designed using advanced technology to present both external and internal antigens effectively, showing promising antigenic activity in preclinical studies.

Preclinical trials demonstrated that 'Grifor' is safe, with no adverse effects observed in experimental animals, including no significant changes in body weight, blood parameters, or immune response, supporting its progression to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development and preclinical study of new generation virosomal split influenza vaccine "Grifor"]. Mel'nikov, SIa., Zverev, VV., Korovkin, SA., et al.[2020]

The engineered trivalent virus-like particle (VLP) vaccine elicited strong immune responses in mice and ferrets, producing hemagglutination-inhibition (HAI) antibodies against both homologous and heterologous influenza strains, indicating broad protection.

Mice vaccinated with the VLP vaccine showed higher levels of influenza-specific CD8+ T cell responses compared to those receiving a standard trivalent inactivated vaccine, and ferrets demonstrated significant protection against disease after being challenged with the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets. Ross, TM., Mahmood, K., Crevar, CJ., et al.[2021]

Citations

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

A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Technology evaluation: FluINsure, ID Biomedical. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical testing of pre-pandemic live attenuated A/H5N2 influenza candidate vaccine in adult volunteers: results from a placebo-controlled, randomized double-blind phase I study. [2022]

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

A Recombinant VSV-Based Bivalent Vaccine Effectively Protects against Both SARS-CoV-2 and Influenza A Virus Infection. [2022]

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]

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

Postlicensure safety surveillance for high-dose trivalent inactivated influenza vaccine in the Vaccine Adverse Event Reporting System, 1 July 2010-31 December 2010. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Active surveillance for influenza vaccine adverse events: the integrated vaccine surveillance system. [2013]

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

Report from enhanced safety surveillance of two influenza vaccines (Vaxigrip and Intanza 15 μg) in two European countries during influenza season 2016/17 and comparison with 2015/16 season. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of quadrivalent recombinant influenza vaccine: Reports to the vaccine adverse event reporting system. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Virosomal influenza vaccine: a safe and effective influenza vaccine with high efficacy in elderly and subjects with low pre-vaccination antibody titers. [2005]

11. England pubmed.ncbi.nlm.nih.gov

Vero cell culture-derived pandemic influenza vaccines: preclinical and clinical development. [2013]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Development and characterization of influenza M2 ectodomain and/or hemagglutinin stalk-based dendritic cell-targeting vaccines. [2023]

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

[Development and preclinical study of new generation virosomal split influenza vaccine "Grifor"]. [2020]

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

A trivalent virus-like particle vaccine elicits protective immune responses against seasonal influenza strains in mice and ferrets. [2021]