LAIV for Flu

(LAIV Trial)

Overseen By Anoma Nellore, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Reactive airway disease, Allergy to LAIV, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how the Live Attenuated Flu Vaccine (LAIV) affects the immune system, particularly by identifying early biomarkers of long-lasting protection. Researchers seek to determine if this nasal spray vaccine can better prepare the body for a subsequent flu shot. This study offers a chance to enhance the understanding of flu vaccines. Individuals who have not received a flu vaccine in the past year and are generally healthy, without conditions like asthma or allergies to the vaccines, may be suitable candidates. As an Early Phase 1 trial, this research focuses on understanding the vaccine's effects in people, providing participants a unique opportunity to contribute to groundbreaking flu vaccine research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it requires participants to be healthy without an immunocompromising condition, which might imply that certain medications affecting the immune system could be excluded.

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

Previous studies have shown that the Live Attenuated Flu Vaccine (LAIV), also known as FluMist, is safe for most people. This vaccine contains live but weakened flu viruses and is designed to help the body build protection against the flu without causing illness.

Research shows that the vaccine is generally well-tolerated. Some individuals might experience mild side effects like a runny nose or sore throat, which usually resolve quickly. People with severe allergies to eggs or other ingredients in the flu vaccine should not receive the LAIV. Additionally, it is not recommended for certain age groups or individuals with specific health conditions.

The vaccine has been used in other countries with safety results similar to regular flu shots. Overall, LAIV is considered safe for healthy individuals who meet the criteria for its use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Live Attenuated Flu Vaccine (LAIV) because it offers a unique approach compared to traditional flu vaccines. Unlike standard flu shots, which use inactivated virus particles, LAIV uses a weakened form of the live virus that helps stimulate a stronger immune response. This can potentially provide broader protection against different strains of the flu. Additionally, LAIV is administered as a nasal spray, making it needle-free and more appealing for those who are needle-averse, such as young children.

What evidence suggests that the Live Attenuated Flu Vaccine (LAIV) might be an effective treatment for flu?

Research shows that the Live Attenuated Flu Vaccine (LAIV), administered to participants in this trial, can help prevent the flu. Studies have found that its effectiveness ranges from 0 to 50%, depending on factors such as the type of flu and the population studied. In everyday situations, LAIV has been about 43% effective compared to not getting vaccinated. This indicates that while LAIV can offer protection, its effectiveness varies. The vaccine uses a weakened form of the flu virus to help the body build defenses against the actual flu. ^{6 7 8 9 10}

Who Is on the Research Team?

Anoma Nellore, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for healthy individuals who haven't had a flu vaccine in the past year and have no history of reactive airway disease or allergies to live or inactivated flu vaccines. They should not have an immunocompromising condition like cancer, autoimmune diseases, organ transplants, or be on steroids.

Inclusion Criteria

No history of allergy to IIV

I consider myself healthy and do not have conditions like cancer, autoimmune diseases, or organ transplants.

You did not get the flu shot last year.

Exclusion Criteria

You cannot consider yourself to be in good health.

You have had an allergic reaction to the live attenuated influenza vaccine (LAIV) or the inactivated influenza vaccine (IIV).

I have a history of asthma or similar lung conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Live Attenuated Influenza Vaccine (LAIV) and are monitored for immune response, followed by an intramuscular influenza vaccination

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood tests to assess T-bet expressing Flu-specific B cell subtypes

7 days

What Are the Treatments Tested in This Trial?

Interventions

• Live Attenuated Flu Vaccine (LAIV)

Trial Overview The study tests if T-bet expressing B cells after receiving the Live Attenuated Flu Vaccine (LAIV) can predict long-lasting antibody responses. Participants will first receive LAIV and then the intramuscular flu vaccine to assess immune protection from both vaccinations.

How Is the Trial Designed?

Group I: Treatment Group Experimental Treatment 1 Intervention

Live Attenuated Flu Vaccine (LAIV) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Flumist for:

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

Approved in European Union as Fluenz Tetra for:

• Prevention of influenza A and B in children and adolescents from 24 months to less than 18 years of age

Approved in Canada as Flumist Quadrivalent for:

• Prevention of influenza A and B in individuals 2 years through 59 years of age

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

FluMist, a live-attenuated influenza vaccine, maintains genetic and phenotypic stability during its manufacturing process, ensuring that critical mutations for cold adaptation, temperature sensitivity, and attenuation are preserved.

Full genome sequencing of multiple influenza strains showed that all vaccine intermediates retained their essential characteristics, confirming the vaccine's safety and efficacy in providing protection against influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic stability of live, cold-adapted influenza virus components of the FluMist/CAIV-T vaccine throughout the manufacturing process. Buonagurio, DA., Bechert, TM., Yang, CF., et al.[2008]

In a study involving 10,169 children and adolescents over four influenza seasons, the live attenuated influenza vaccine (LAIV) showed a vaccine effectiveness (VE) of 69% against influenza A(H1N1)pdm09, which is comparable to the 79% effectiveness of the inactivated influenza vaccine (IIV).

The study found no significant differences in effectiveness between LAIV and IIV for most influenza types, suggesting that both vaccines are effective options for preventing influenza in children aged 2 to 17 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Live Attenuated vs Inactivated Influenza Vaccines in Children During the 2012-2013 Through 2015-2016 Influenza Seasons in Alberta, Canada: A Canadian Immunization Research Network (CIRN) Study. Buchan, SA., Booth, S., Scott, AN., et al.[2019]

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 live attenuated influenza vaccine (LAIV) is effective in protecting children aged ≤71 months against influenza, showing superior efficacy compared to the trivalent inactivated influenza vaccine (TIV) in several studies, particularly in younger children.

LAIV is generally well tolerated, with mild to moderate side effects, but it is not recommended for children under 24 months due to an increased risk of wheezing and hospitalization in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Live attenuated influenza vaccine (FluMist®; Fluenz™): a review of its use in the prevention of seasonal influenza in children and adults. Carter, NJ., Curran, MP.[2022]

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]

An improved live attenuated influenza vaccine (LAIV) for mice has been developed that significantly enhances safety, achieving a 10,000-fold increase in safety while maintaining the same attenuating mutations as the human version.

This modified vaccine shows a trade-off with a 20-fold decrease in protective efficacy, indicating a balance between safety and effectiveness for high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single Mutation at PB1 Residue 319 Dramatically Increases the Safety of PR8 Live Attenuated Influenza Vaccine in a Murine Model without Compromising Vaccine Efficacy. Cox, A., Dewhurst, S.[2021]

Live attenuated influenza vaccines (LAIVs) are considered more effective than inactivated vaccines because they stimulate a broader range of immune responses, including antibodies and cell-mediated immunity.

Current research is focused on developing new LAIV approaches, with ongoing evaluations of their safety and effectiveness in humans, indicating a promising future for these vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity and infectivity of new live attenuated influenza vaccines. Isakova-Sivak, I., Rudenko, L.[2022]

In a study of 344 subjects aged 5-49 years, the incidence of vaccine virus shedding after receiving the live attenuated influenza vaccine (LAIV) was highest in younger age groups, with 44% of 5-8 year-olds shedding the virus compared to only 17% of 18-49 year-olds, indicating that younger individuals may have a stronger response to the vaccine.

The shedding of the vaccine virus was generally short-lived and occurred at low levels, peaking on day 2 post-vaccination, which supports guidelines that LAIV recipients should only avoid contact with severely immunosuppressed individuals for 7 days after vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shedding and immunogenicity of live attenuated influenza vaccine virus in subjects 5-49 years of age. Block, SL., Yogev, R., Hayden, FG., et al.[2022]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7319054/

Successes and Failures of the Live-attenuated Influenza ... Live-attenuated influenza vaccine (LAIV) studies have found effectiveness ranging from 0–50%. Using mathematical models we show that this can be the result of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X25002439

Real-world effectiveness of influenza vaccination in ... Compared to unvaccinated children, LAIV-4 had an overall effectiveness of 43 % (95 % CI, 32 %–53 %), while IIV effectiveness was 54 % (95 % CI, ...

3. cdc.gov cdc.gov/mmwr/volumes/74/wr/mm7406a2.htm

Interim Estimates of 2024–2025 Seasonal Influenza ... Effectiveness against influenza A(H3N2) was 51% (IVY) against influenza-associated hospitalization but was not statistically significant in the ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/14760584.2025.2536087

a systematic literature review and network meta-analysis Real-world studies generally report moderate VE against influenza (approximately 40–60%) [Citation32], which is expected due to antigenic drift. This results in ...

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/302147

Effectiveness of Live, Attenuated Intranasal Influenza Virus ... Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated.

6. cdc.gov cdc.gov/vaccine-safety/vaccines/flu.html

Influenza (Flu) Vaccine Safety CDC and FDA monitor the safety of flu vaccines. FDA must license the vaccine, and it must be appropriate for the recipient's age and health ...

7. fda.gov fda.gov/files/Package-Insert-FluMist-Quadrivalent.pdf

Package Insert - FluMist Quadrivalent Data on safety and shedding of vaccine virus after ... FluMist and FluMist Quadrivalent contain live attenuated influenza viruses that must infect and replicate.

8. flumist.com flumist.com/

FluMist® (Influenza Vaccine Live, Intranasal) | Nasal Spray Flu ... Important Safety Information. You should not get FLUMIST if you have a severe allergy to its components, eggs or other flu vaccines; or are 2 ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5861790/

Influenza vaccines: Evaluation of the safety profile - PMC The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods.

10. cdc.gov cdc.gov/flu/vaccine-types/nasalspray.html

Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray ... Data from other countries have demonstrated protection from LAIV to be similar to that of standard-dose, egg-based inactivated flu vaccine in ...