H1ssF-3928 Vaccine for Influenza

No longer recruiting at 1 trial location

Overseen By Emmanuel Walter

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunosuppressive condition, Neoplastic disease, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new mRNA vaccine for the flu to determine its safety and effectiveness at different doses. Healthy volunteers will receive either the new vaccine or a standard flu shot to compare immune responses. The trial seeks participants who are in good health, have received at least one flu shot in the past five years, and have no ongoing health issues. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding how it works in people.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications. However, any changes in chronic prescription medication should not have occurred in the 60 days prior to enrollment, unless they are due to a change of healthcare provider or insurance. You can continue taking chronic or as-needed medications if they pose no additional risk to your safety or the study's assessments.

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

Research shows that the H1ssF-3928 mRNA vaccine is undergoing testing to ensure its safety for humans. In this early phase, researchers assess how well participants tolerate the vaccine and monitor for any side effects. Previous studies have shown that mRNA vaccines, like those for COVID-19, are generally well-tolerated. Most reactions, if they occur, are mild, such as soreness at the injection site or a slight fever.

The trial is carefully designed to start with a low dose, increasing to higher doses only if no safety issues arise. This gradual approach helps minimize risks. The goal is to find the safest dose that remains effective. As this is an early-stage trial, safety is the top priority, and only healthy adults participate. This allows for close monitoring and management of any side effects that might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the H1ssF-3928 mRNA vaccine for influenza because it uses cutting-edge mRNA technology, which is different from traditional flu vaccines that typically use inactivated or live attenuated viruses. This mRNA vaccine works by instructing cells to produce a protein found on the influenza virus, triggering an immune response without using the actual virus. The potential for rapid production and efficient adaptation to emerging flu strains makes this vaccine particularly promising compared to existing options like the Quadrivalent Influenza Vaccine (IIV4). Additionally, the different dosage arms being tested could help determine the most effective and safe dose, offering a tailored approach to flu prevention.

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

Research shows that the H1ssF-3928 mRNA-LNP vaccine is designed to help the body fight the flu. This vaccine uses mRNA, a small piece of genetic material, to instruct cells to produce a part of the flu virus, enabling the immune system to recognize and combat the virus. Similar mRNA vaccines have demonstrated a strong immune response. Although data on this specific vaccine is limited, it employs the same mRNA technology as the COVID-19 vaccines, which have proven effective. This trial includes various treatment arms to evaluate different dosages of the H1ssF-3928 mRNA vaccine and compares it with a licensed Quadrivalent Influenza Vaccine (IIV4). Early studies focus on confirming the vaccine's safety and its ability to boost immunity. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Healthy adults aged 18-49, with stable blood pressure and pulse, a BMI of 18 to <35 kg/m^2, who've had an influenza vaccine in the last five seasons. Women must not be pregnant or breastfeeding and agree to contraception. Excludes those with immune conditions, recent drug abuse, psychiatric hospitalization, or certain medication use.

Inclusion Criteria

Body mass index (BMI) of 18 kg/m^2 (inclusive) to <35 kg/m^2 at screening

Provide written informed consent prior to initiation of any study procedure

I have had a flu shot in the last 5 years.

Exclusion Criteria

Has a positive urine toxicology screen

My lab results show mild abnormalities.

I have not been sick or had a fever in the last 3 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of H1ssF 3928 mRNA Vaccine at varying doses (10 mcg, 25 mcg, 50 mcg) or a licensed quadrivalent influenza vaccine (IIV4)

1 day

1 visit (in-person)

Safety Monitoring

Participants are monitored for reactogenicity and adverse events through Day 8, with specific focus on sentinel subgroups

8 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events of special interest (AESIs)

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VRC H1ssF-3928 mRNA-LNP

Trial Overview The trial is testing a new mRNA-LNP flu vaccine called H1ssF_3928 at different doses (10 mcg, 25 mcg, and 50 mcg) against a licensed quadrivalent flu vaccine. It's an open-label study where healthy volunteers receive one dose intramuscularly to evaluate safety and immune response.

How Is the Trial Designed?

Group I: Arm 4, Optimal Dose Experimental Treatment 2 Interventions

10 healthy adult volunteer subjects from 18-49 years of age will receive the selected optimal dose of the H1ssF\_3928 mRNA Vaccine, administered intramuscularly once. The optimal dosing group will be selected based on safety outcomes from the 10 mcg, 25 mcg, and 50 mcg dosing groups. For the optimal dose, the highest dose with no identified safety concerns as determined by the Safety Review Committee (SRC) will be selected. N =10

Group II: Arm 3, High Dose Experimental Treatment 2 Interventions

10 healthy adult volunteer subjects from 18-49 years of age are split into two subgroups. The sentinel subgroup includes 2 vaccine recipients who will receive 50 mcg of the H1ssF\_3928 mRNA Vaccine, administered intramuscularly once. The sentinel subgroup is observed for 8 days to monitor any early vaccine related adverse events. After the observation period, the remaining participants will receive the same dosage, 50 mcg of the H1ssF 3928 mRNA vaccine administered intramuscularly once. N = 10

Group III: Arm 2, Medium Dose Experimental Treatment 2 Interventions

10 healthy adult volunteer subjects from 18-49 years of age are split into two subgroups. The sentinel subgroup includes 2 vaccine recipients who will receive 25 mcg of the H1ssF\_3928 mRNA Vaccine, administered intramuscularly once. The sentinel subgroup is observed for 8 days to monitor any early vaccine related adverse events. After the observation period, the remaining participants will receive the same dosage, 25 mcg of the H1ssF 3928 mRNA vaccine administered intramuscularly once. N = 10

Group IV: Arm 1, Low Dose Experimental Treatment 2 Interventions

10 healthy adult volunteer subjects from 18-49 years of age are split into two subgroups. The sentinel subgroup includes 2 vaccine recipients who will receive 10 mcg of the H1ssF\_3928 mRNA Vaccine, administered intramuscularly once. The sentinel subgroup is observed for 8 days to monitor any early vaccine related adverse events. After the observation period, the remaining participants will receive the same dosage, 10 mcg of the H1ssF 3928 mRNA vaccine administered intramuscularly once. N = 10

Group V: Arm 5, IIV4 Active Control 1 Intervention

10 healthy adult volunteer subjects from 18-49 years of age will receive licensed Quadrivalent Influenza Vaccine (IIV4), administered intramuscularly once. Subjects receiving IIV4 will be followed for safety, but only their immune responses will be compared to those of participants receiving H1ssF\_3928 mRNA Vaccine. N=10

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 quadrivalent mRNA-1010 vaccine demonstrated strong humoral immunogenicity, eliciting higher hemagglutination inhibition (HAI) titers against influenza A strains compared to a standard inactivated vaccine, indicating its potential effectiveness in preventing influenza.

No significant safety concerns were reported during the trial, although mild adverse reactions were more common with mRNA-1010, suggesting it is generally safe for use in healthy adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis. Lee, IT., Nachbagauer, R., Ensz, D., et al.[2023]

The novel combined mRNA vaccine AR-CoV/IAV, which targets both COVID-19 and influenza A, successfully generated strong immune responses in mice, producing protective antibodies and cellular immunity against both viruses.

Immunization with AR-CoV/IAV effectively protected mice from severe outcomes associated with coinfection of influenza A and SARS-CoV-2 variants, demonstrating the potential of this vaccine platform for preventing respiratory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational development of a combined mRNA vaccine against COVID-19 and influenza. Ye, Q., Wu, M., Zhou, C., et al.[2023]

A quadrivalent mRNA vaccine targeting four seasonal influenza virus strains was shown to induce strong antibody responses in mice, with effective protection against illness even at low doses (as low as 1 μg per antigen).

The mRNA vaccine demonstrated the ability to prevent weight loss and protect against morbidity and mortality from influenza, highlighting its potential as a promising alternative to traditional influenza vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection. Kackos, CM., DeBeauchamp, J., Davitt, CJH., et al.[2023]

The study developed a lipid nanoparticle-encapsulated mRNA vaccine targeting a consensus hemagglutinin (HA) sequence, which showed strong immunogenicity and protective efficacy against various H1N1 influenza viruses in mice after two doses.

The H1c-mRNA-LNP vaccine induced robust antibody responses and both Th1 and Th2 cellular immune responses, with a stronger Th1 response, suggesting it could be a promising candidate for a broadly protective influenza vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an mRNA vaccine against a panel of heterologous H1N1 seasonal influenza viruses using a consensus hemagglutinin sequence. Ma, N., Xia, ZW., Zhang, ZG., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05755620

NCT05755620 | A Study to Evaluate the Safety and ... The primary objective of this study is to assess the safety of a single dose of VRC H1ssF 3928 mRNA-LNP vaccine administered IM in healthy adults, 18-49 yrs, ...

2. nih.gov nih.gov/news-events/news-releases/clinical-trial-mrna-universal-influenza-vaccine-candidate-begins

Clinical trial of mRNA universal influenza vaccine ... This Phase 1 trial will test the experimental vaccine, known as H1ssF-3928 mRNA-LNP, for safety and its ability to induce an immune response.

3. trialx.com trialx.com/clinical-trials/listings/280521/a-study-to-evaluate-the-safety-and-immunogenicity-of-a-single-dose-of-h1ssf-3928-mrna-lnp-in-healthy-adults/

A Study to Evaluate the Safety and Immunogenicity ... The primary objective of this study is to assess the safety of a single dose of VRC H1ssF 3928 mRNA-LNP vaccine administered IM in healthy ...

4. niaidcivics.org niaidcivics.org/clinical-studies/

Clinical Studies The primary objective of this study is to assess the safety and immunogenicity of a single dose of the VRC H1ssF 3928 mRNA-LNP vaccine administered ...

5. ivr.cidrap.umn.edu ivr.cidrap.umn.edu/universal-influenza-vaccine-technology-landscape

Universal Influenza Vaccine Technology Landscape Styles 2025 evaluated immunogenicity and efficacy in the presence of pre-existing immunity of an influenza virus chimeric HA (cH8/1 and cH5/1) vaccine prime- ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05755620/a-study-to-evaluate-the-safety-and-immunogenicity-of-a-single-dose-of-h1ssf-3928-mrna-lnp-in-healthy-adults

A Study to Evaluate the Safety and Immunogenicity ... This study is designed to assess the safety and immunogenicity of one dose of H1ssF 3928 mRNA Vaccine. Eligible participants will be sequentially enrolled into ...