H1ssF-3928 Vaccine for Influenza

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

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a Phase 1, single-site, open-label, comparator-controlled dose escalating study of an intramuscularly (IM) administered mRNA-LNP vaccine encoding for (Vaccine Research Center) VRC H1ssF 3928 of up to 50 healthy adult volunteers aged 18 to 49 years, inclusive. 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 dosing groups (10 mcg, 25 mcg, and 50 mcg, selected optimal dose) to receive the H1ssF 3928 mRNA Vaccine at the specified dose. A separate group of 10 participants will receive licensed quadrivalent influenza vaccine (IIV4). 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. Dosing of H1ssF 3928 mRNA Vaccine will commence at the lowest dose (10 mcg) and only escalate to the next highest dose if safety concerns are not identified. Up to ten subjects will be enrolled per dosing cohort. Reactogenicity and adverse event (AE) information through Day 7 and clinical laboratory results through Day 8 from the first three dosing groups will guide the selection of an optimal dose group to include 10 subjects who will receive the optimal dose of mRNA-LNP. 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, at doses of 10 mcg, 25 mcg, and 50 mcg.

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.

How is the H1ssF-3928 vaccine for influenza different from other treatments?

The H1ssF-3928 vaccine is unique because it uses a lipid nanoparticle-encapsulated mRNA platform to encode a consensus full-length hemagglutinin (HA) sequence, aiming to provide broad protection against various H1N1 influenza strains. This approach is different from traditional vaccines that target specific strains, as it can potentially overcome issues of antigenic mismatch due to viral mutations. ^{1 2 3 4 5}

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

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]

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]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection. [2023]

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

Immunogenicity and efficacy of flagellin-fused vaccine candidates targeting 2009 pandemic H1N1 influenza in mice. [2021]

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

Development of an mRNA vaccine against a panel of heterologous H1N1 seasonal influenza viruses using a consensus hemagglutinin sequence. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Rational development of a combined mRNA vaccine against COVID-19 and influenza. [2023]

5. England 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. [2023]