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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new flu vaccine called FluMos-v2 in healthy adults. Researchers aim to determine if this vaccine can protect against multiple flu virus strains, unlike current vaccines that target only one strain. Participants will receive two shots of the vaccine in their upper arm and must track their temperature and any skin changes at the injection site for a week after each shot. Healthy adults who haven't experienced serious vaccine reactions and are willing to attend multiple clinic visits over 10 months might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the FluMos-v2 vaccine aims to protect against several types of the flu virus. It is currently undergoing tests to ensure safety for healthy adults. In earlier studies, the vaccine was generally well-tolerated, with most people experiencing only mild side effects. Some reported temporary soreness at the injection site or a slight fever, common reactions to many vaccines.

This trial is in an early stage, so researchers focus primarily on assessing its safety. Although detailed information from past trials is limited, early-stage trials are conducted with great care and close monitoring to ensure safety. Participants in this study will receive careful observation, with several follow-up visits to check for any side effects. These early trials are crucial for ensuring a new treatment's safety before further testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about FluMos-v2 because it represents a new approach to flu vaccination. Unlike traditional flu vaccines, which typically use inactivated or weakened viruses, FluMos-v2 is a mosaic nanoparticle vaccine designed to target multiple strains of the influenza virus simultaneously. This means it could potentially offer broader protection against the flu, reducing the need for annual vaccine updates. Additionally, the trial is testing different dosages, exploring whether a higher dose might provide even stronger immunity. If successful, FluMos-v2 could simplify and enhance flu prevention strategies, making them more effective across various flu seasons.

What evidence suggests that this trial's treatments could be effective for influenza?

Research has shown that current flu vaccines are effective against only one strain of the virus. The new experimental vaccine, FluMos-v2, which trial participants will receive, aims to protect against multiple strains. Early studies suggest that FluMos-v2 might be more effective because it targets several types of flu viruses simultaneously. This could offer broader protection than traditional vaccines. Although still under testing, the goal is to reduce severe flu cases and deaths worldwide by covering more virus types. ^{1 2 6 7 8}

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

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 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]

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 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]

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 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]

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]

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 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]

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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05968989?term=NCT05968989

Study Details | NCT05968989 | Trial to Evaluate the Safety, ... Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Mosaic Hexavalent Influenza Vaccine VRC-FLUMOS0116-00-VP (FluMos-v2) in Healthy Adults.

2. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=001614-I&&query=Mosaic%2018

Protocol Details Current vaccines work well against single strains of flu virus. But no single vaccine works well against all flu viruses that can cause illness. Objective: To ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06863142

Study Details | NCT06863142 | Evaluating the Dose, Safety ... This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of mosaic hexavalent influenza vaccine VRC- ...

4. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=002293-I&&query=

002293-I FluMos-v2 is an experimental flu vaccine; ALFQ is an experimental adjuvant. ... -- Receipt of the mosaic hexavalent influenza vaccine VRC-FLUMOS0116-00-VP (FluMos ...

5. trialx.com trialx.com/clinical-trials/listings/297383/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/

Clinical Research Trial Listing ( Influenza Prevention This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of mosaic hexavalent influenza vaccine.

6. niaid.nih.gov niaid.nih.gov/clinical-trials/experimental-influenza-vaccine-flumos-v2-study

Experimental Influenza Vaccine (FluMos-v2) Study | NIAID The primary purpose of this study is to see if the experimental influenza (flu) vaccine called the FluMos-v2 vaccine is safe, and to determine ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06863142/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

Evaluating the Dose, Safety, Tolerability, and ... This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of mosaic hexavalent influenza vaccine VRC- ...

8. trialx.com trialx.com/clinical-trials/listings/248959/trial-to-evaluate-the-safety-tolerability-and-immunogenicity-of-a-mosaic-hexavalent-influenza-vaccine-vrc-flumos0116-00-vp-flumos-v2-in-healthy-adults/

Clinical Research Trial Listing ( Influenza ) ( NCT05968989 ) This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of the mosaic hexavalent ...