DCVC H1 HA mRNA Vaccine for Flu

Not currently recruiting at 1 trial location

Overseen By Patricia L. Winokur

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunosuppressants, Corticosteroids, Chemotherapy, others

Disqualifiers: Immunosuppressive conditions, Neoplastic disease, Psychiatric illness, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

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 by evaluating its safety and effectiveness in triggering an immune response in healthy adults. Participants will receive two doses of the experimental DCVC H1 HA mRNA vaccine, while another group will receive a standard flu shot for comparison. The trial seeks healthy individuals who have not experienced flu symptoms or received a flu shot in the past 90 days. 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. However, certain medications like corticosteroids and high-dose inhaled steroids should not be taken within 30 days before the study vaccination. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mRNA vaccines, such as the DCVC H1 HA mRNA vaccine, have been well-tolerated in past studies. These studies generally find that mRNA vaccines can cause mild side effects, including pain at the injection site, fatigue, or mild fever. These side effects are usually temporary.

The DCVC H1 HA mRNA vaccine is currently being tested in an early phase study, which primarily focuses on ensuring safety. The study begins with low doses and only increases them if no safety concerns arise. This careful approach ensures that any side effects are manageable and understood before progressing to higher doses. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the DCVC H1 HA mRNA vaccine for flu because it utilizes cutting-edge mRNA technology, which is different from the traditional inactivated virus vaccines like Fluzone Quadrivalent. The mRNA vaccine works by instructing cells to produce a protein that triggers an immune response, potentially offering more precise protection against flu strains. Additionally, the mRNA platform allows for quicker updates to the vaccine to match circulating flu strains, which could lead to more effective and timely flu prevention. Unlike standard flu shots that use killed virus particles, this mRNA vaccine could offer a novel and adaptable approach to flu vaccination.

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

Research into mRNA vaccines, such as the DCVC H1 HA mRNA vaccine, shows they can trigger strong immune responses. This trial will test different doses of the DCVC H1 HA mRNA vaccine, with participants receiving either 10 mcg, 25 mcg, or 50 mcg doses. The vaccine uses mRNA technology, which has succeeded in other vaccines, to teach the body how to fight the flu virus. The goal is for the vaccine to help the immune system recognize and attack the flu virus more effectively. Early research suggests that mRNA vaccines might offer broader and longer-lasting protection against the flu compared to traditional vaccines. However, specific data on the effectiveness of the DCVC H1 HA mRNA vaccine in people is still being collected. While promising, this vaccine is still under study for its effectiveness. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Healthy adults aged 18-49 with stable blood pressure, not pregnant or breastfeeding, and without significant health conditions can join. They must agree to use contraception and avoid sperm donation for specified periods around vaccination. Exclusions include drug abuse, liver disease, immune disorders, recent corticosteroid use, severe reactions to vaccines, certain heart conditions, psychiatric hospitalization within the past 5 years.

Inclusion Criteria

I can follow the study's procedures and attend all visits.

I agree not to donate sperm and to use contraception for 90 days after my last vaccine dose.

Provide written informed consent prior to initiation of any study procedure

Exclusion Criteria

I have had Guillain-Barré Syndrome in the past.

Has a positive urine toxicology screen

I have a history of heart inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of DCVC H1 HA mRNA vaccine administered 28 days apart

4 weeks

2 visits (in-person)

Safety Evaluation

Safety Review Committee evaluates safety data to determine dose escalation

1 week

Follow-up

Participants are monitored for safety and immunogenicity after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• DCVC H1 HA mRNA vaccine
• Quadrivalent Recombinant Seasonal Influenza Vaccine

Trial Overview The trial is testing a new mRNA vaccine (DCVC H1 HA) against H1N1 influenza in healthy adults. Participants will receive varying doses (10 mcg up to an optimal dose determined by safety outcomes) compared with a standard quadrivalent flu vaccine. The study aims to find the safest effective dose.

How Is the Trial Designed?

Group I: Arm 3 Experimental Treatment 2 Interventions

Healthy adults, 18 to 49 years of age will receive 50 mcg of DCVC H1 HA mRNA vaccine administered intramuscularly to the upper arm/deltoid at days 1 and 29. A safety evaluation will occur to ensure the safety data support proceeding to the optimal dose group. N = 20

Group II: Arm 2 Experimental Treatment 2 Interventions

Healthy adults, 18 to 49 years of age will receive 25 mcg of DCVC H1 HA mRNA vaccine administered intramuscularly to the upper arm/deltoid at days 1 and 29. A dose escalation safety evaluation will occur to ensure the safety data support proceeding to the higher dose group. N = 10

Group III: Arm 1 Experimental Treatment 2 Interventions

Healthy adults, 18 to 49 years of age will receive 10 mcg of DCVC H1 HA mRNA Vaccine administered intramuscularly to the upper arm/deltoid at days 1 and 29. A dose escalation safety evaluation will occur to ensure the safety data support proceeding to the higher dose group. N = 10

Group IV: Arm 4 Active Control 3 Interventions

Healthy adults, 18 to 49 years of age will receive 60 mcg of Licensed quadrivalent inactivated influenza vaccine (IIV4), Fluzone Quadrivalent, administered intramuscularly to the upper arm/deltoid once. 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 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]

An mRNA lipid nanoparticle vaccine targeting the hemagglutinin glycoprotein from the highly pathogenic H5 clade 2.3.4.4b avian influenza virus has been developed and shown to be immunogenic in both mice and ferrets.

The vaccine effectively prevents illness and death in ferrets after exposure to the H5N1 virus, indicating its potential as a protective measure against this strain of avian influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus. Furey, C., Ye, N., Kercher, L., et al.[2023]

A combined mRNA-LNP vaccine targeting four different influenza A antigens was shown to effectively induce strong immune responses in mice after just one dose, demonstrating its potential for a universal influenza vaccine.

The quadrivalent formulation provided protection against various influenza viruses, including a challenging H1N1 strain, with minimal side effects, indicating its efficacy and safety at a low antigen dose of 125 ng per component.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses. McMahon, M., O'Dell, G., Tan, J., et al.[2023]

A new influenza virus vaccine candidate using nucleoside-modified mRNA encoding the hemagglutinin (HA) stalk has shown promise in inducing strong antibody responses in mice, rabbits, and ferrets.

Immunization with this HA mRNA vaccine not only generated antibodies against the HA stalk but also provided protection against various strains of influenza, indicating its potential as a broadly protective vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. Pardi, N., Parkhouse, K., Kirkpatrick, E., et al.[2020]

In a 6-week study involving 169 patients with mild to moderate asthma, fluticasone propionate (FP) at 2 x 250 micrograms/day was found to be significantly more effective than flunisolide (FLUN) at 2 x 500 micrograms/day, with 79% of FP patients showing improvement compared to 57% for FLUN (p = 0.02).

FP demonstrated greater efficacy in reducing symptoms like dyspnea and cough, particularly in patients with lower lung function (FEV1), while both treatments were generally well-tolerated and deemed safe by the majority of participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Controlled clinical comparative evaluation of fluticasone powder inhalation versus flunisolide dose aerosol in patients with mild to moderate asthma]. Bergmann, KC.[2021]

In a trial involving 106 chronic-progressive patients, Cop 1 showed a lower confirmed progression rate on the disability scale compared to placebo, with 20.4% of Cop 1 patients progressing versus 29.5% in the placebo group over two years.

The study found significant differences in unconfirmed progression rates and progression of 0.5 EDSS units, indicating that Cop 1 may help slow disease progression in chronic-progressive patients, although overall survival curves were not significantly different.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Bornstein, MB., Miller, A., Slagle, S., et al.[2019]

Influenza vaccination is associated with a significantly lower risk of developing ventricular arrhythmia (VA) in patients with chronic obstructive pulmonary disease (COPD), based on a study of 18,658 patients over 12 years.

Patients with specific health conditions (CHA2DS2-VASc scores of 2-3) who received one or more influenza vaccinations showed even greater reductions in VA risk, suggesting that vaccination could be a beneficial preventive measure for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza Vaccination and the Risk of Ventricular Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease: A Population-Based Longitudinal Study. Chen, CC., Lin, CH., Hao, WR., et al.[2021]

The IMPACT trial, involving 10,355 patients, showed that the combination therapy of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) significantly reduced the rate of moderate or severe exacerbations in patients with symptomatic COPD compared to other combinations.

Patients using FF/UMEC/VI reported clinically meaningful improvements in health-related quality of life and symptoms, as measured by the St George's Respiratory Questionnaire and other assessments, over 52 weeks, indicating its efficacy as a once-daily treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Inhaler Triple Therapy and Health-Related Quality of Life in COPD: The IMPACT Study. Tabberer, M., Jones, CE., Kilbride, S., et al.[2022]

The corrected hypercapnic ventilation response (CHCVR) is a more reliable measure of chemosensitivity in patients with poor lung function, such as those with chronic obstructive pulmonary disease (COPD), compared to the standard hypercapnic ventilation response (HCVR).

In a study involving 34 COPD patients and 19 patients with low FEV1 due to small stature, CHCVR demonstrated high sensitivity (86%) and specificity (100%), indicating it is a valuable tool for assessing respiratory function in ventilation-limited patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypercapnic ventilation response in patients with lung disease: improved accuracy by correcting for ventilation ability. Jones, RL., Neary, JM., Man, GC., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05945485

NCT05945485 | A Study to Evaluate the Safety and ... This study is designed to assess the safety and immunogenicity of two doses of DCVC H1 HA mRNA vaccine administered 28 days apart. Eligible participants will be ...

2. niaidcivics.org niaidcivics.org/clinical-studies/

Clinical Studies Description: This clinical trial will assess the safety and immunogenicity of two doses of an mRNA-LNP vaccine, DCVC H1 HA mRNA Vaccine, developed by the Duke ...

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

Universal Influenza Vaccine Technology Landscape Vaccine candidates profiled in the Landscape are designed to provide broader and more durable protection against seasonal and pandemic influenza, compared with ...

4. withpower.com withpower.com/trial/phase-1-influenza-human-6-2023-5ed63

DCVC H1 HA mRNA Vaccine for Flu The research does not provide direct evidence about the effectiveness of the DCVC H1 HA mRNA vaccine for flu, but it does suggest that influenza vaccination in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11206352/

Brief Insights into mRNA Vaccines: Their Successful ... A mRNA vaccine is a type of vaccine that induces an immune response. Antigen-encoding mRNA is delivered via vaccine carriers into the immune ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10790309/

A multivalent nucleoside-modified mRNA vaccine against ... Here, we generated a nucleoside-modified mRNA-LNP vaccine expressing HA antigens from all known influenza virus subtypes and found that this ...

7. synapse.patsnap.com synapse.patsnap.com/drug/cb51d2b2d43d484892dee6117b3d16d0

DCVC H1 HA mRNA vaccine(National Institute of Allergy ... A Phase 1, Comparator-Controlled, Dosage-Escalation Study to Evaluate the Safety and Immunogenicity of Two Doses of DCVC H1 HA mRNA-LNP in Healthy Adults.