Influenza Vaccine for Flu

Overseen By Sokratis Apostolidis, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Pennsylvania

Must not be taking: Immunosuppressants

Disqualifiers: Febrile illness, Active malignancy, 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 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

75 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial excludes people using immunosuppressing medications, so if you are on these, you would need to stop taking them to participate.

Is the influenza vaccine generally safe for humans?

The influenza vaccine, including various forms like Fluzone Quadrivalent and Afluria Quadrivalent, has been studied for safety in different groups, including pregnant women, older adults, and children. Most reported side effects are mild, such as injection site reactions, fever, and headache, with serious events being rare. Overall, the vaccine is considered safe based on these studies. ^{1 2 3 4 5}

How is the influenza vaccine treatment different from other flu treatments?

The influenza vaccine is unique because it includes a quadrivalent formulation, which means it protects against four different strains of the flu virus, including two influenza A subtypes and two B types. This broader protection helps reduce the risk of the vaccine not matching the dominant circulating B strain, offering better protection compared to trivalent vaccines that only cover three strains. ^{4 6 7 8 9}

What is the purpose of this trial?

Better understanding of the immune responses to influenza vaccination is needed in order to understand situations of poor vaccine response. Adults will receive influenza vaccination and then have peripheral blood drawn at pre-defined intervals in order to study the lymphocyte responses.

Research Team

E.John Wherry, PhD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults who can consent and need a flu shot as part of their regular health care. It's not for those with a fever, cancer, on drugs that suppress the immune system, who've donated blood recently or had a flu shot in the last 6 months, or have allergies to flu vaccines.

Inclusion Criteria

I live at home, can make my own decisions, and need a flu shot.

Exclusion Criteria

You have donated blood in the last 60 days.

I have received the flu vaccine in the last 6 months.

I currently have cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one intramuscular dose of seasonal quadrivalent inactivated influenza vaccine

1 day

1 visit (in-person)

Follow-up

Participants have peripheral blood drawn at pre-defined intervals to study lymphocyte responses

4-8 weeks

Treatment Details

Interventions

• Influenza vaccination

Trial Overview The study involves giving participants an influenza vaccine and then taking samples of their blood at set times afterwards to analyze how their immune cells respond to the vaccination.

Participant Groups

Group I: Influenza vaccination cohort Experimental Treatment 1 Intervention

Adults will receive one intramuscular dose of seasonal quadrivalent inactivated influenza vaccine, as indicated for standard of care.

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

Approved in European Union as Influenza Vaccination for:

• Prevention of influenza A and B infections in individuals aged 6 months and older

Approved in United States as Influenza Vaccination for:

• Prevention of influenza A and B infections in individuals aged 6 months and older

Approved in Canada as Influenza Vaccination for:

• Prevention of influenza A and B infections in individuals aged 6 months and older

Approved in Japan as Influenza Vaccination for:

• Prevention of influenza A and B infections in individuals aged 6 months and older

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

The high-dose quadrivalent influenza vaccine (QIV-HD) was approved for individuals 65 years and older, and a review of 2,122 adverse event reports showed that 95.1% were non-serious, aligning with findings from prelicensure trials.

No new safety concerns were identified, with the most common serious events being Guillain-Barré syndrome and local reactions, suggesting that QIV-HD is a safe option for preventing influenza in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. Woo, EJ., Moro, PL.[2022]

A new active surveillance system called SICOVA was developed in Mexico to monitor adverse events (AEs) following quadrivalent influenza vaccination, involving 2013 participants over three influenza seasons.

The overall adverse event rate was 9.09%, with most AEs being mild and not requiring medical visits, confirming the established safety profile of the Fluzone® Quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved post-marketing safety surveillance of quadrivalent inactivated influenza vaccine in Mexico using a computerized, SMS-based follow-up system. Betancourt-Cravioto, M., Cervantes-Powell, P., Tapia-Conyer, R., et al.[2022]

The Fluzone® Quadrivalent (IIV4) vaccine was monitored for safety in pregnant women, with 239 exposure reports collected from August 2013 to September 2019, showing no new safety concerns related to maternal or neonatal outcomes.

Among the reported outcomes, over 85% of neonates were full-term births, and all infants with available information had normal APGAR scores, indicating that the vaccine is safe for use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry. Ledlie, S., Gandhi-Banga, S., Shrestha, A., et al.[2022]

The quadrivalent influenza vaccine S-IIV4 demonstrated noninferior immunogenicity compared to the US-licensed C-IIV4 in a study involving 2,247 children aged 6-59 months, indicating it effectively stimulates the immune response against influenza strains.

S-IIV4 was associated with lower rates of fever (5.8%) compared to C-IIV4 (8.4%), suggesting improved safety in terms of febrile reactions, with no reports of febrile convulsions in either vaccine group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6-59 months of age: A phase 3, randomized, noninferiority study. Statler, VA., Albano, FR., Airey, J., et al.[2019]

The quadrivalent influenza vaccine AdimFlu-S showed strong immunogenicity in a study of 174 healthy children aged 3 to 17, achieving high seroprotection rates above 96.4% for all vaccine strains.

The vaccine was well tolerated with no serious adverse events reported over a 6-month follow-up period, indicating it is a safe option for improving protection against different influenza B lineages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in healthy subjects aged 3 to 17 years old: A phase III, open label, single-arm study. Chang, CY., Cho, CY., Lai, CC., et al.[2021]

VaxigripTetra™ (IIV4) is a quadrivalent influenza vaccine that has been shown to be immunogenic and well tolerated in individuals aged 3 years and older, based on phase III clinical trial results.

The addition of a second B strain in IIV4 enhances the immune response without compromising the response to the other three strains or affecting safety, potentially leading to greater protection against influenza-related illnesses compared to trivalent vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quadrivalent inactivated influenza vaccine (VaxigripTetra™). Gresset-Bourgeois, V., Leventhal, PS., Pepin, S., et al.[2018]

The D-QIV vaccine, which includes two A and two B influenza strains, has shown to be highly immunogenic in large trials involving healthy adults and children, meeting and exceeding vaccine licensure criteria.

D-QIV was well tolerated across all age groups and demonstrated superior immune responses against the additional B strain compared to traditional trivalent vaccines, potentially offering better protection against circulating influenza viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inactivated quadrivalent split-virus seasonal influenza vaccine (Fluarix® quadrivalent): a review of its use in the prevention of disease caused by influenza A and B. McKeage, K.[2022]

In a pilot study involving 385 children and adolescents, the most common adverse event following the Fluenz Tetra nasal vaccine was nasal congestion, reported by 43.4% of participants, indicating that while side effects occurred, they were generally mild.

No serious adverse events or hospitalizations were reported, suggesting that the Fluenz Tetra vaccine is safe for use in children, with no significant safety concerns identified during the 2014/2015 influenza season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Intranasal Quadrivalent Live Attenuated Influenza Vaccine (QLAIV) in Children and Adolescents: A Pilot Prospective Cohort Study in England. McNaughton, R., Lynn, E., Osborne, V., et al.[2018]

The Fluzone Intradermal (ID) vaccine was found to be as immunogenic as the standard intramuscular (IM) vaccine, showing no significant differences in antibody responses for all three viral strains tested.

While the ID vaccine had higher rates of local reactions like erythema and swelling compared to the IM vaccine, it was well-tolerated overall, with no serious adverse events reported, indicating it can be safely used for annual revaccination in adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age. Gorse, GJ., Falsey, AR., Johnson, CM., et al.[2013]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. [2022]

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

Improved post-marketing safety surveillance of quadrivalent inactivated influenza vaccine in Mexico using a computerized, SMS-based follow-up system. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in children 6-59 months of age: A phase 3, randomized, noninferiority study. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in healthy subjects aged 3 to 17 years old: A phase III, open label, single-arm study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Quadrivalent inactivated influenza vaccine (VaxigripTetra™). [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Inactivated quadrivalent split-virus seasonal influenza vaccine (Fluarix® quadrivalent): a review of its use in the prevention of disease caused by influenza A and B. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Safety of Intranasal Quadrivalent Live Attenuated Influenza Vaccine (QLAIV) in Children and Adolescents: A Pilot Prospective Cohort Study in England. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age. [2013]