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

50 Participants Needed

Trial Summary

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 data supports the idea that Nasal Spray Vaccine for Flu is an effective treatment?

The available research does not provide any data on the effectiveness of the Nasal Spray Vaccine for Flu. Instead, it focuses on treatments for allergic rhinitis and hay fever, such as the P-FN12-based vaccine and other immunotherapies. Therefore, there is no information here to support the effectiveness of the Nasal Spray Vaccine for Flu. ^{1 2 3 4 5}

What safety data exists for the nasal spray flu vaccine?

The nasal spray flu vaccine, known as FluMist or LAIV, has been shown to be generally safe and well-tolerated in healthy individuals aged 5-49 years. Common side effects include abdominal pain, chills, cough, diarrhea, headache, irritability, lethargy, muscle aches, otitis media, rhinitis, sinusitis, sore throat, and vomiting. The vaccine has been licensed in the U.S. since 2003 and was updated to a quadrivalent formulation in 2012. Concerns about effectiveness led to a temporary recommendation against its use in 2016-17 and 2017-18, but it was recommended again for the 2018-19 season. Studies have shown genetic and phenotypic stability of the vaccine during manufacturing, and no transmission to close contacts was detected in previous studies. ^{6 7 8 9 10}

Is the nasal spray vaccine FluMist a promising treatment for the flu?

Yes, FluMist, a nasal spray vaccine, is a promising treatment for the flu. It is effective in preventing influenza and is well tolerated in healthy people aged 5 to 49. The nasal spray method is less painful than a shot, making it more appealing, especially for children. ^{6 7 9 10 11}

What is the purpose of this trial?

The goals of this study are to better understand the human immune response to influenza vaccines, specifically the live attenuated (weakened) influenza vaccine given as a nasal spray. Better understanding why this vaccine does not work as well in adults as it does in children may help design better influenza vaccines.

Research Team

Daniel Graciaa, MD, MPH, MSc

Principal Investigator

Emory University

Eligibility Criteria

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

I understand the study and can agree to participate.

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.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States 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. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[Effect and safety analysis of Allergovit standardized mite allergen immunotherapy in patients with allergic rhinitis]. [2014]

3. China pubmed.ncbi.nlm.nih.gov

[Safety analysis of Allergovit immunotherapy in patients of allergic rhinitis]. [2014]

4. England pubmed.ncbi.nlm.nih.gov

Pollinex Quattro Tree: allergy vaccine. [2019]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Immunovac-VP4 vaccine used in complex allergen-specific immunotherapy of patients with hay fever]. [2020]

6. 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]

7. 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]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Genetic stability of live, cold-adapted influenza virus components of the FluMist/CAIV-T vaccine throughout the manufacturing process. [2008]

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

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

10. 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]

11. Netherlands 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. [2015]