Live Attenuated Influenza Vaccine for Flu

Overseen By David LaFon, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alabama at Birmingham

Must not be taking: Immune suppressing medications

Disqualifiers: Immunocompromising, Asthma, Diabetes, Pregnancy, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

25 Participants Needed

Trial Summary

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-suppressing medications, you may not be eligible to participate.

What data supports the effectiveness of the drug FluMist Quadrivalent Nasal Product for preventing the flu?

Clinical trials have shown that the live attenuated influenza vaccine (FluMist) is effective in preventing influenza, with a protective efficacy of 92% in young children and significant protection against strains not contained in the vaccine. It is well tolerated in healthy individuals aged 5-49 years and offers a convenient intranasal administration without the need for injections. ^{1 2 3 4 5}

Is the live attenuated influenza vaccine (FluMist) safe for humans?

FluMist, a live attenuated influenza vaccine, is generally well tolerated in healthy individuals aged 5-49 years, with common side effects including mild symptoms like cough and sore throat. Studies have shown it to be safe, with no transmission detected to close contacts, and it has been safely tested in immunocompromised ferrets, suggesting potential safety in similar human populations. ^{1 2 5 6 7}

What makes the FluMist Quadrivalent Nasal Product unique compared to other flu treatments?

FluMist Quadrivalent is unique because it is a nasal spray vaccine that contains live, weakened viruses, unlike most flu vaccines which are injections with inactivated (killed) viruses. It also covers four strains of the flu virus, including both B lineages, reducing the risk of mismatch with circulating strains. ^{8 9 10 11 12}

What is the purpose of this trial?

The purpose of this study is to develop a nasal model for influenza infection using the live attenuated influenza vaccine (LAIV). The investigators will administer LAIV to healthy adult volunteers in order to simulate influenza infection, and obtain nasal specimens to measure influenza virus and inflammatory/immune responses. In a subset of participants, cystic fibrosis transmembrane conductance regulator (CFTR) function will also be evaluated via measurement of nasal potential difference (NPD)

Eligibility Criteria

Healthy adults aged 18-49 who haven't had the flu vaccine for the current season can join. They must be able to consent to participate. People with chronic health issues, recent respiratory infections, heart failure, Guillain-Barre syndrome, pregnancy, egg allergies or contact with immunocompromised individuals cannot join.

Inclusion Criteria

I have not received the flu vaccine for 2019-2020.

I am able to understand and sign the consent form.

I have not received the flu vaccine for 2019-2020.

Exclusion Criteria

You have smoked cigarettes in the last 6 months.

I have a heart condition other than just high blood pressure.

I have asthma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive the live attenuated influenza vaccine (LAIV) to simulate influenza infection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for influenza virus replication and inflammatory response

2 days

1 visit (in-person)

Treatment Details

Interventions

• Flumist Quadrivalent Nasal Product

Trial Overview The study is testing a nasal spray flu vaccine called Flumist Quadrivalent to develop a model of influenza infection. Participants will receive this live vaccine and researchers will collect nasal samples to study virus presence and immune responses.

Participant Groups

Group I: open label Experimental Treatment 1 Intervention

FLUMIST QUADRIVALENT 0.2 mL dose supplied in a single-dose pre-filled intranasal sprayer

Flumist Quadrivalent Nasal Product is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as FluMist Quadrivalent for:

• Prevention of influenza A and B viruses in individuals aged 2 through 49 years

Approved in European Union as Fluenz Tetra for:

• Prevention of influenza A and B viruses in individuals aged 2 through 49 years

Approved in Canada as FluMist for:

• Prevention of influenza A and B viruses in individuals aged 2 through 49 years

Approved in Japan as FluMist for:

• Prevention of influenza A and B viruses in individuals aged 2 through 49 years

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

In a study of 197 healthy children aged 9 to 36 months, 80% of those who received the live attenuated influenza vaccine (LAIV) shed at least one vaccine strain, indicating effective viral replication and immune response.

Despite high shedding rates, the probability of transmitting the vaccine strain to unvaccinated contacts was very low at 0.58%, and no significant safety concerns or adverse events were reported in either the vaccinated or placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine. Vesikari, T., Karvonen, A., Korhonen, T., et al.[2011]

FluMist is an effective intranasal vaccine for preventing influenza A and B, showing good tolerance in healthy individuals aged 5-49 years based on clinical trials.

The vaccine offers a painless alternative to traditional injections, although barriers such as patient eligibility, cost, and insurance coverage may affect its acceptance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination for the pediatric patient: a focus on the new intranasal, cold-adapted, live attenuated vaccine. Ellis, JM., Reilly, JC., Salazar, JC.[2021]

The cold adapted live attenuated influenza vaccine (CAIV-T, FluMist) has shown a high protective efficacy of 92% against culture-confirmed influenza in young children over a two-year study, demonstrating its effectiveness as a preventive measure.

In adults, CAIV-T not only induced a broad immune response even when the vaccine strain did not match the epidemic strain but also effectively reduced febrile upper respiratory illnesses and days missed from work, highlighting its overall effectiveness in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of live attenuated influenza virus vaccine in the US. Belshe, RB.[2005]

The live attenuated influenza vaccine (LAIV) is administered intranasally and is effective in preventing influenza in children and adolescents aged 2 to under 18 years, eliciting a strong immune response.

LAIV is well tolerated and has a safety profile comparable to placebo, supported by clinical trials and the administration of over 39 million doses, contributing to herd immunity against seasonal influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Live attenuated influenza vaccine (Fluenz™): a guide to its use in the prevention of seasonal influenza in children in the EU. Scott, LJ., Carter, NJ., Curran, MP.[2021]

The quadrivalent live attenuated influenza vaccine (LAIV4) was reintroduced as a recommended option for the 2018-19 influenza season after being previously sidelined due to concerns about its effectiveness against certain influenza strains.

The decision to reinstate LAIV4 was based on a thorough review of data and methodology, indicating that it could be a suitable vaccination choice for specific populations, despite past effectiveness issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update: ACIP Recommendations for the Use of Quadrivalent Live Attenuated Influenza Vaccine (LAIV4) - United States, 2018-19 Influenza Season. Grohskopf, LA., Sokolow, LZ., Fry, AM., et al.[2019]

The live attenuated influenza vaccine (LAIV; FluMist) was found to be safe for use in immunocompromised ferrets, showing no adverse effects after administration.

Immunocompromised ferrets demonstrated antibody responses to the vaccine that were comparable to those of healthy control ferrets, suggesting that LAIV could be an effective alternative for preventing influenza in immunocompromised patients, such as those undergoing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Live attenuated influenza vaccine is safe and immunogenic in immunocompromised ferrets. Huber, VC., McCullers, JA.[2013]

The live attenuated influenza vaccine (LAIV) tested in ferrets was found to be significantly less virulent than the wild-type H1N1 virus, indicating a strong safety profile.

The LAIV induced strong immune responses and effectively protected ferrets from symptoms and lesions associated with H3N2 influenza virus infection, demonstrating its efficacy as a vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a candidate live attenuated influenza vaccine prepared in Changchun BCHT (China) for safety and efficacy in ferrets. Shen, Z., Bowen, RA., Ge, P., et al.[2018]

Influenza vaccines are crucial for protecting high-risk groups, and trained nurses play a key role in ensuring these individuals receive their vaccinations.

Nurses are responsible for auditing high-risk populations and ordering the necessary vaccine doses in advance, highlighting the importance of proactive healthcare measures in the spring and summer for effective vaccination in the autumn.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination. Cook, R.[2019]

A short 2-minute training session significantly improved the quality of face-mask ventilation (FMV) among 26 local healthcare providers in Togo, reducing mask leak from 89.7% to 45.4% after training and further to 18.3% with additional feedback.

The training also increased the percentage of breaths within the recommended peak inspiratory pressure (PIP) range, demonstrating that brief training can effectively enhance critical ventilation skills in low-resource settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a short training on neonatal face-mask ventilation performance in a low resource setting. Mazza, A., Cavallin, F., Cappellari, A., et al.[2018]

The inactivated influenza vaccine (IIV) showed a moderate effectiveness of 47% against hospitalization due to influenza-associated acute respiratory infections in individuals aged 50 and older in rural Thailand during 2010-2011, based on a study of 1545 patients.

Despite this effectiveness, vaccination coverage was low, with only 5% of influenza-positive patients and 9% of control patients having received the vaccine, indicating a need for increased vaccination efforts in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of the 2010 and 2011 Southern Hemisphere trivalent inactivated influenza vaccines against hospitalization with influenza-associated acute respiratory infection among Thai adults aged ≥ 50 years. Dawood, FS., Prapasiri, P., Areerat, P., et al.[2021]

Community pharmacies, like Walgreens, play a crucial role in providing influenza vaccinations, especially in medically underserved areas (MUAs), where they administered over one-third of all flu shots during the 2009-10 season.

In states with high populations in MUAs, pharmacies provided an even greater percentage of vaccinations, reaching up to 77.1%, highlighting their importance in improving access to immunizations for vulnerable communities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacy provision of influenza vaccinations in medically underserved communities. Murphy, PA., Frazee, SG., Cantlin, JP., et al.[2012]

The study predicts that using quadrivalent influenza vaccines (QIVs) instead of trivalent vaccines (TIVs) could prevent 16% more cases of influenza B lineage infections in the U.S. from 2000-2013, particularly benefiting the elderly and young seniors.

Even with varying levels of cross-protection between B lineages, the QIV could lead to significant reductions in influenza cases, suggesting that routine vaccination with QIV could greatly enhance public health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective public health impact of a quadrivalent influenza vaccine in the United States. Crépey, P., de Boer, PT., Postma, MJ., et al.[2018]

References

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

A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine. [2011]

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

Influenza vaccination for the pediatric patient: a focus on the new intranasal, cold-adapted, live attenuated vaccine. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Current status of live attenuated influenza virus vaccine in the US. [2005]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Live attenuated influenza vaccine (Fluenz™): a guide to its use in the prevention of seasonal influenza in children in the EU. [2021]

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

Update: ACIP Recommendations for the Use of Quadrivalent Live Attenuated Influenza Vaccine (LAIV4) - United States, 2018-19 Influenza Season. [2019]

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

Live attenuated influenza vaccine is safe and immunogenic in immunocompromised ferrets. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Evaluation of a candidate live attenuated influenza vaccine prepared in Changchun BCHT (China) for safety and efficacy in ferrets. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Influenza vaccination. [2019]

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

Effect of a short training on neonatal face-mask ventilation performance in a low resource setting. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Effectiveness of the 2010 and 2011 Southern Hemisphere trivalent inactivated influenza vaccines against hospitalization with influenza-associated acute respiratory infection among Thai adults aged ≥ 50 years. [2021]

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

Pharmacy provision of influenza vaccinations in medically underserved communities. [2012]

12. England pubmed.ncbi.nlm.nih.gov

Retrospective public health impact of a quadrivalent influenza vaccine in the United States. [2018]