mRNA Vaccine for Flu

Recruiting at 17 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Immune-modifying drugs

Disqualifiers: Influenza, Malignancy, Immunodeficient, Neurological, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 1 day

843 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this study is to assess the safety and immune response of GlaxoSmithKlines (GSK) messenger RNA (mRNA)-based multivalent vaccine (GSK4382276A) candidate against influenza, administered in healthy younger adults (YA) and older adults (OA).

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immune-modifying drugs, you may need to stop them at least 3 months before the study. It's best to discuss your specific medications with the trial investigator.

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 immune-modifying drugs or have had recent vaccinations, you may need to discuss this with the study team.

What safety data exists for the mRNA flu vaccine?

The interim analysis of a phase 1/2 clinical trial for the mRNA-based seasonal influenza vaccine, mRNA-1010, showed no safety concerns. Solicited adverse reactions were dose-dependent and more frequent compared to the active comparator. These findings support the continued development of mRNA-1010. ^{1 2 3 4 5}

Is the mRNA flu vaccine generally safe for humans?

In a clinical trial of the mRNA flu vaccine (mRNA-1010), no safety concerns were identified, although some mild reactions were more common with the vaccine than with a standard flu shot. This suggests the vaccine is generally safe for humans. ^{1 2 3 4 5}

Is the treatment GSK4382276A a promising treatment for flu?

Yes, mRNA vaccines, like GSK4382276A, show promise for flu treatment because they can quickly adapt to new virus strains, boost immune responses, and provide broad protection against different types of flu viruses. ^{1 6 7 8 9}

How is the mRNA vaccine GSK4382276A different from other flu treatments?

The mRNA vaccine GSK4382276A is unique because it targets internal proteins of the influenza virus, inducing a strong T cell response that provides broad protection against various strains, unlike traditional vaccines that focus on surface proteins and may vary in effectiveness each year. ^{6 7 8 9 10}

What data supports the idea that mRNA Vaccine for Flu (also known as: GSK4382276A, GSK4382276A) is an effective treatment?

The available research shows that mRNA vaccines for flu are effective because they can quickly produce a strong immune response. In ferrets, the mRNA vaccine boosted immune cells that help fight off the flu, and in mice, it provided full protection against flu symptoms. The vaccine also worked well in very young and very old mice, which is important because these groups are often more vulnerable to the flu. Additionally, the mRNA vaccine was as effective as a licensed flu vaccine in pigs, suggesting it could be a strong alternative to current flu vaccines. ^{6 7 8 11 12}

What data supports the effectiveness of the mRNA vaccine treatment GSK4382276A for flu?

Research shows that mRNA vaccines can boost immune responses and provide protection against various strains of the flu virus in animals like ferrets and mice. These vaccines are designed to quickly adapt to new virus strains, making them a promising option for flu prevention. ^{6 7 8 11 12}

Are You a Good Fit for This Trial?

This trial is for healthy adults, both young and older, who are interested in participating in a study to evaluate the immune response and safety of various mRNA-based flu vaccine formulations. Specific health criteria must be met to join.

Inclusion Criteria

Written informed consent obtained from the participant prior to performance of any study-specific procedure

Participants who can and will comply with the requirements of the protocol, independently or with the assistance of a caregiver

Body mass index (BMI) >=18 kg/m² and <=35 kg/m²

Exclusion Criteria

Hypersensitivity to latex

Concurrent participation in another clinical study involving investigational interventions

I have ongoing seizures or neurological issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 1 dose of the study intervention or active comparator intramuscularly on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including solicited and unsolicited adverse events

26 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GSK4382276A

Trial Overview The trial is testing multiple mRNA flu vaccine formulations against influenza. Participants will receive one of several new vaccine candidates or an existing comparator vaccine to assess their immune responses and safety profiles.

How Is the Trial Designed?

Group I: Flu mRNA_YA_Group 5 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group II: Flu mRNA_YA_Group 4 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group III: Flu mRNA_YA_Group 3 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group IV: Flu mRNA_YA_Group 2 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group V: Flu mRNA_YA_Group 1 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group VI: Flu mRNA_OA_Group 5 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group VII: Flu mRNA_OA_Group 4 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group VIII: Flu mRNA_OA_Group 3 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group IX: Flu mRNA_OA_Group 2 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group X: Flu mRNA_OA_Group 1 Experimental Treatment 1 Intervention

Eligible participants receive 1 dose of study intervention at Day 1 intramuscularly.

Group XI: YA_Active Comparator Group 1 Active Control 1 Intervention

Eligible participants receive 1 dose of an active comparator at Day 1 intramuscularly.

Group XII: OA_Active Comparator Group 2 Active Control 1 Intervention

Eligible participants receive 1 dose of an active comparator at Day 1 intramuscularly.

Group XIII: YA_Active Comparator Group 3 Active Control 1 Intervention

Eligible participants receive 1 dose of an active comparator at Day 1 intramuscularly.

Group XIV: OA_Active Comparator Group 4 Active Control 1 Intervention

Eligible participants receive 1 dose of an active comparator at Day 1 intramuscularly.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

A novel mRNA vaccine targeting conserved proteins of the H1N1 influenza virus successfully induced broadly reactive T cells in both naïve and influenza-experienced ferrets, suggesting its potential effectiveness in diverse populations.

The booster vaccination significantly enhanced protection against a different strain of influenza (H7N9), indicating that this mRNA vaccine strategy could provide robust immunity against evolving influenza viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets. van de Ven, K., Lanfermeijer, J., van Dijken, H., 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]

A new quadrivalent influenza vaccine using a bicistronic self-amplifying mRNA platform successfully induced antibodies against both hemagglutinin (HA) and neuraminidase (NA), enhancing immune responses compared to traditional vaccines that focus only on HA.

The inclusion of NA in the vaccine not only improved protection against antigenically drifted strains but also provided greater overall protection in ferrets against the A(H3N2) virus, highlighting the potential for broader immunity with this innovative vaccine approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Self-amplifying mRNA seasonal influenza vaccines elicit mouse neutralizing antibody and cell-mediated immunity and protect ferrets. Cheung, M., Chang, C., Rathnasinghe, R., et al.[2023]

mRNA vaccines for influenza have been shown to induce strong and long-lasting immunity in both very young and very old mice, demonstrating their potential effectiveness across age groups.

These vaccines not only provide protection against influenza A virus but also target multiple viral antigens, suggesting they could serve as cross-protective vaccines, similar in efficacy to licensed vaccines in larger animals like pigs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Petsch, B., Schnee, M., Vogel, AB., et al.[2021]

mRNA vaccines have shown promising results in providing specific protection against viral infections in animal studies, indicating their potential for use in human clinical trials.

These vaccines combine the safety and simplicity of subunit vaccines with the immunological benefits of live viral vaccines, allowing for precise control over their immunogenic profile and the ability to induce strong immune responses without the complications associated with traditional vaccine production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Messenger RNA-based vaccines: progress, challenges, applications. Kramps, T., Probst, J.[2021]

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]

A post-marketing surveillance study from 2005 to 2019 identified 36 safety signals for the influenza vaccine, including 7 that were not previously labeled, highlighting the need for ongoing monitoring of vaccine safety.

Specific adverse events, such as application site disorders, were more common with quadrivalent and cell-based vaccines, while trivalent and egg-based vaccines showed a broader range of adverse events, indicating different safety profiles among vaccine types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing surveillance study on influenza vaccine in South Korea using a nationwide spontaneous reporting database with multiple data mining methods. Lee, H., Hong, B., Kim, S., et al.[2023]

Cardiac complications, particularly myopericarditis, were the most frequently reported severe adverse events associated with mRNA COVID-19 vaccines, with systemic reactions being more common after the second dose.

Despite the higher number of reported adverse effects following the Pfizer vaccine, the review concluded that the overall benefits of mRNA vaccines in controlling the COVID-19 pandemic significantly outweigh the risks of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Adverse Events Related to COVID-19 mRNA Vaccines; a Systematic Review. SeyedAlinaghi, S., Karimi, A., Pashaei, Z., et al.[2022]

The 2009 AS03 adjuvanted pandemic vaccine was found to have a good safety profile, with a 7% reporting rate of health events among 6242 healthcare workers, compared to 4.3% for the seasonal trivalent influenza vaccine (TIV) in 7645 participants.

While the pandemic vaccine had more local reactions (1% vs. 0.03%), it did not show any clustering of serious adverse events during a six-month follow-up, indicating it is generally safe for use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short and long-term safety of the 2009 AS03-adjuvanted pandemic vaccine. De Serres, G., Gariépy, MC., Coleman, B., et al.[2021]

A review of 531 reports of adverse events following influenza vaccination over three seasons found that while 6% were serious, most were not directly linked to the vaccine, indicating a generally safe profile for influenza vaccines.

The most common adverse events included injection site inflammation, headache, myalgia, and pyrexia, with extensive limb swelling reported in 26 cases, but no new unknown side effects were identified, supporting the safety of influenza vaccinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Reported adverse events following influenza vaccination]. van Balveren-Slingerland, L., Rümke, HC., Kant, AC.[2018]

mRNA vaccines that encode for influenza hemagglutinin (HA) antigens from all known subtypes and lineages can stimulate a broad immune response.

These mRNA vaccines are effective in generating cross-reactive and protective immunity against various strains of the influenza virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiplexing mRNAs builds a "broad-immunity wall" against the flu. Catanzaro, NJ., Martinez, DR.[2023]

The mRNA-lipid nanoparticle vaccine has been shown to provide protection against 20 different lineages of the influenza virus, indicating its broad efficacy.

This innovative vaccine approach utilizes lipid nanoparticles to deliver mRNA, which instructs cells to produce viral proteins, prompting an immune response that can recognize and combat multiple influenza strains.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influenza universe in an mRNA vaccine. Kelvin, AA., Falzarano, D.[2023]

Citations

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

A universal influenza mRNA vaccine candidate boosts T cell responses and reduces zoonotic influenza virus disease in ferrets. [2023]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Self-amplifying mRNA seasonal influenza vaccines elicit mouse neutralizing antibody and cell-mediated immunity and protect ferrets. [2023]

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

Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. [2021]

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

Messenger RNA-based vaccines: progress, challenges, applications. [2021]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Post-marketing surveillance study on influenza vaccine in South Korea using a nationwide spontaneous reporting database with multiple data mining methods. [2023]

8. Iran pubmed.ncbi.nlm.nih.gov

Safety and Adverse Events Related to COVID-19 mRNA Vaccines; a Systematic Review. [2022]

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

Short and long-term safety of the 2009 AS03-adjuvanted pandemic vaccine. [2021]

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

[Reported adverse events following influenza vaccination]. [2018]

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

Multiplexing mRNAs builds a "broad-immunity wall" against the flu. [2023]

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

The influenza universe in an mRNA vaccine. [2023]