Nasal Spray Vaccine for Flu

(PRISM Trial)

Overseen By Daniel Graciaa, MD, MPH, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Immune modifiers, Systemic steroids

Disqualifiers: Impaired immunity, Asthma, HIV, 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: 3

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a nasal spray flu vaccine, focusing on why it appears less effective in adults than in children. Understanding this difference could lead to improved flu vaccines in the future. Participants will receive a single dose of the live, weakened influenza vaccine, known as the Live Attenuated Influenza Vaccine (LAIV). It suits those who haven't recently had the flu or a flu shot and don't have serious health issues like severe heart or lung disease. Individuals with asthma or certain immune conditions should not participate. As a Phase 4 trial, this study involves an FDA-approved vaccine and aims to understand its benefits for more patients.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using immune-modifying drugs or have had a change in medication for chronic conditions in the past 3 months, you may be excluded from the trial.

What is the safety track record for the Live Attenuated Influenza Vaccine?

Research has shown that the live attenuated influenza vaccine (LAIV), administered as a nasal spray, is generally safe for most people. The CDC recommends this flu vaccine for everyone aged six months and older. Studies have found that both children and adults usually tolerate LAIV well.

Safety data indicate that common side effects are mild and may include a runny nose or sore throat, which typically resolve on their own. The vaccine is not suitable for individuals with severe allergies to its ingredients or to eggs.

The vaccine is widely used and has a strong safety record, supported by years of data. It is already approved for preventing flu in different age groups, providing a good level of safety evidence for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the live attenuated influenza vaccine (LAIV) nasal spray because it offers a needle-free alternative to traditional flu shots, making it more appealing for those who are needle-averse. Unlike standard flu vaccines that use inactivated virus, this nasal spray uses a weakened form of the live virus to stimulate a stronger immune response. This delivery method could potentially provide broader and longer-lasting protection against the flu, while also simplifying the vaccination process, especially for children and those who prefer to avoid injections.

What is the effectiveness track record for the live attenuated influenza vaccine?

Studies have shown that the nasal spray flu vaccine, known as the live attenuated influenza vaccine (LAIV), works moderately well. From 2010 to 2023, it was about 49% to 51% effective, preventing about half of the flu cases in the groups studied. In children, the nasal spray works about as well as other flu vaccines. However, it has not been as effective in adults. Researchers continue to study why this occurs. ^{5 6 7 8 9}

Who Is on the Research Team?

Daniel Graciaa, MD, MPH, MSc

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals who want to help researchers understand the immune response to flu vaccines, particularly the nasal spray vaccine that's weaker and works differently in adults compared to children. Specific eligibility criteria are not provided.

Inclusion Criteria

Participants of childbearing potential must agree to use effective birth control for the duration of the study. A negative urine pregnancy test must be documented prior to vaccination.

I understand the study and can agree to participate.

Exclusion Criteria

Body Mass Index (BMI) > 35

I haven't had a fever or cold symptoms, nor taken fever reducers in the last 72 hours.

I have a condition that weakens my immune system, but skin cancers or cured solid tumors don't apply.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of the live attenuated influenza vaccine (LAIV) as a nasal spray

1 day

1 visit (in-person)

Follow-up

Participants are monitored for immune response and safety, with biologic samples collected from blood and nose

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Live Attenuated Influenza Vaccine

Trial Overview The study focuses on the live attenuated influenza vaccine given as a nasal spray. It aims to reveal why this flu vaccine's effectiveness varies between adults and children by studying participants' immune responses.

How Is the Trial Designed?

Group I: Live Attenuated Influenza Vaccine Experimental Treatment 1 Intervention

Participants receiving a single dose of the live attenuated influenza vaccine (LAIV).

Live Attenuated Influenza Vaccine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as FluMist for:

• Prevention of influenza disease caused by influenza A subtype viruses and type B viruses in persons 2 through 49 years of age

Approved in European Union as Fluenz Tetra for:

• Prevention of influenza disease in children and adolescents

Approved in Canada as FluMist for:

• Prevention of influenza disease caused by influenza A subtype viruses and type B viruses in persons 2 through 49 years of age

Approved in Japan as FluMist for:

• Prevention of influenza disease caused by influenza A subtype viruses and type B viruses in persons 2 through 49 years of age

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Boston University

Collaborator

Trials

494

Recruited

9,998,000+

Published Research Related to This Trial

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]

In the 2013-2014 influenza season, 12.7 million doses of the quadrivalent live attenuated influenza vaccine (LAIV4) were distributed, with 95% of the 779 reports to VAERS being non-serious, indicating a favorable safety profile for healthy individuals aged 2-49 years.

The analysis revealed no concerning patterns in serious adverse events, but highlighted the need for better education and screening regarding vaccine administration, especially for individuals for whom LAIV4 is not recommended, such as pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-licensure surveillance of quadrivalent live attenuated influenza vaccine United States, Vaccine Adverse Event Reporting System (VAERS), July 2013-June 2014. Haber, P., Moro, PL., Cano, M., et al.[2015]

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]

A study involving 425 patients over three years showed that Allergovit standardized dust mite immunotherapy significantly improved quality of life and reduced nasal symptoms in individuals with allergic rhinitis.

The treatment was found to be safe, with low rates of local reactions (3.15%) and systemic reactions (0.90%), indicating it can be a reliable option for managing allergic rhinitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect and safety analysis of Allergovit standardized mite allergen immunotherapy in patients with allergic rhinitis]. Zhao, X., Wu, H., Lin, L., et al.[2014]

Pollinex Quattro (PQ) Tree is a novel allergy vaccine that has been shown to be effective and safe for treating seasonal rhinitis in both children and adults, based on various clinical trials since its development in 1999.

This allergy immunotherapy requires only four pre-seasonal injections, offering a shorter treatment course while providing similar efficacy and safety compared to traditional grass allergy formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pollinex Quattro Tree: allergy vaccine. Gawchik, SM., Saccar, CL.[2019]

The bacterial therapeutic vaccine Immunovac-VP4, administered before allergen-specific immunotherapy (ASIT), significantly improved clinical and immunological outcomes in 69 patients with hay fever and asthma, leading to an 8.5 times lower incidence of acute respiratory infections compared to the control group.

After 7 years, 90% of patients reported prolonged remission from symptoms, indicating that the use of natural ligands of Toll-like receptors in immunotherapy could be a promising strategy for treating allergic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunovac-VP4 vaccine used in complex allergen-specific immunotherapy of patients with hay fever]. Poddubikova, AM., Kostinov, MP.[2020]

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]

The peptide P-FN12, targeting the histamine H4 receptor, was developed into a vaccine that significantly reduced allergic symptoms in a rat model of allergic rhinitis, demonstrating its potential as a novel treatment.

The vaccine not only decreased levels of allergen-specific IgE but also shifted the immune response from a Th2-dominant profile to a Th1-dominant profile, suggesting a mechanism for its efficacy in reducing allergic inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P-FN12, an H4R-Based Epitope Vaccine Screened by Phage Display, Regulates the Th1/Th2 Balance in Rat Allergic Rhinitis. Wang, Y., Sha, J., Wang, H., et al.[2020]

FluMist is a safe and effective intranasal influenza vaccine approved by the FDA, which may be more acceptable for children compared to traditional injections.

While it offers benefits in vaccination, there is a concern about the shedding of live virus, which could pose risks to individuals with weakened immune systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Demystifying FluMist, a new intranasal, live influenza vaccine. Mossad, SB.[2019]

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]

In a study of 256 patients with allergic rhinitis, Allergovit immunotherapy demonstrated a high safety profile, with only 4.45% experiencing local side effects and 0.31% experiencing systemic side effects, both of which were mild.

The results suggest that Allergovit is a safe and feasible treatment option for allergic rhinitis, although adjustments to the treatment schedule may be necessary for better individualization in practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety analysis of Allergovit immunotherapy in patients of allergic rhinitis]. Chen, J., Xiang, J., Kong, W., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6005581/

The safety and efficacy of quadrivalent live attenuated ... Quadrivalent live attenuated influenza vaccine did not meet its primary efficacy endpoint as only a single infection by a vaccine‐matched strain was detected.

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

a systematic literature review and network meta-analysis For the 2010–11 to 2016–17 and 2017–18 to 2022–23 time periods, the pooled estimates of LAIV aVE were 49% (95% CI: 39, 57) and 51% (95% CI: 39, 60), ...

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

Real-world effectiveness of influenza vaccination in ... Conclusions. An overall moderate, comparable effectiveness of LAIV-4 and IIV in preventing influenza/ILI among Italian children was observed.

4. flumisthcp.com flumisthcp.com/about-flumist/vaccine-effectiveness-and-efficacy

Vaccine Effectiveness | For HCPs In the study among controls: 48% QIV, 13% aQIV, 10% QIV-HD, 8% QIVc, 8% LAIV (trivalent and quadrivalent), 2% TIV, and 12% unknown.

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

Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray ... Because of limited use, there have been no effectiveness estimates in the United States since LAIV was recommended again in the 2018-2019 ...

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

Package Insert - FluMist Quadrivalent Data on safety and shedding of vaccine virus after administration of FluMist in immunocompromised persons are limited to 173 persons with HIV infection and 10 ...

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

Influenza (Flu) Vaccine Safety CDC recommends annual flu vaccination for everyone ages 6 months and older with any flu vaccine licensed by FDA that is appropriate for the recipient's age and ...

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. ema.europa.eu ema.europa.eu/en/documents/product-information/fluenz-tetra-epar-product-information_en.pdf

Fluenz Tetra, INN-influenza-vaccine-(live-attenuated,-nasal) Safety data regarding use of Fluenz Tetra are based on data from Fluenz Tetra clinical studies in 2,231 children and adolescents 2 to 17 years of age, Fluenz ...