Mucosal and Systemic Immunity After Viral Challenge of Healthy Volunteers Vaccinated With Inactivated Influenza Vaccine Via the Intranasal Versus Intramuscular Route

NCT03845231 | Completed Phase 2 FDA Drug

• 2 other identifiers: 19005819-I-0058
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Influenza (flu) is a contagious respiratory virus that makes humans sick. Usually its symptoms are mild, but they can be dangerous. Researchers want to see if one way of giving the flu vaccine is more effective than another. Objective: To compare the body s ability to fight infection when a flu vaccine is given in the nose versus the arm. Eligibility: Healthy, nonsmoking adults ages 18 55. They must be willing to stay in isolation for at least 9 days. They must not have had the flu vaccine since September 1, 2018. Design: Participants must be willing to use birth control or abstinence from visit 1 until 8 weeks after getting the flu virus. Participants will have at least 3 clinic visits over about a month. Visits may include: Medical history Physical exam Blood and urine tests Nasal samples collected Heart and lung function tests At the first visit, participants will get either: Flu vaccine as injection in an arm muscle plus salt water sprays in the nose OR flu vaccine as sprays in the nose plus salt water injection in an arm Within the next few months, participants will stay in an isolation room for at least 9 days. They will be with up to 20 participants. Those who test positive for recreational drugs will leave the study. Participants will: Repeat study tests Answer questions about flu symptoms Have the flu virus sprayed into their nose once Be monitored by a medical team Participants will have at least 2 follow-up visits and repeat study tests.

Conditions

Influenza

Keywords

Human Challenge; Vaccine; Immune Response; Challenge Study; Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• Influenza infection

  The main focus of the study will be to characterize the mucosal and systemic immunologic correlates of protection from influenza infection in each of the two cohorts.

  1 yr

Study Arms (2)

unvaccinated

OTHER

will receive no Flucelvax vaccination and will receive human challenge virus

Other: Human Challenge virus

Vaccinated

EXPERIMENTAL

will receive Flucelvax vaccination and human challenge virus

Biological: Flucelvax(R); Other: Human Challenge virus

Interventions

Flucelvax(R) BIOLOGICAL

Cohort 1 will receive IM quadrivalent IIV (Flucelvax (R)) at the standard dose of 15 micrograms HA per strain (60 micrograms HA total).

Vaccinated

Human Challenge virus OTHER

A dose of 10\^7 50% tissue culture infective dose (TCID50) of human challenge virus will be administered intranasally to all participants using a nasal sprayer.

Vaccinated; unvaccinated

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Greater than or equal to 18 and less than or equal to 55 years of age.
• Non-smoker.
• Have not received influenza vaccination of any type (whether licensed or unlicensed experimental vaccine) on or after September 1, 2018. Participants who enroll in our study must be informed of the Centers for Disease Control and Prevention (CDC) recommendation to receive seasonal influenza vaccination annually. Enrollees accept that half of study participants will receive licensed approved vaccination per the usual route, and half will receive it by an unapproved route with unknown efficacy and side effects. Enrollees should not plan to receive seasonal influenza vaccination from another source from enrollment through the final study visit (Phase 2, Day 56).
• Willingness to remain in isolation for the duration of viral shedding (at a minimum 9 days) and to comply with all study requirements.
• A male subject is eligible for the study if he meets one of the following criteria, beginning at least 4 weeks prior to enrollment and continuing until 8 weeks after administration of the human challenge virus:
• Is infertile, including history of successful vasectomy.
• Agrees to practice abstinence.
• A female participant is eligible for this study if she is not pregnant or breastfeeding and meets one of the following criteria, beginning at least 4 weeks prior to enrollment and continuing until 8 weeks after administration of the human challenge virus::
• infertile, including postmenopausal status, (as defined by no menses for greater than or equal to 1 year) or history of hysterectomy.
• Agrees to practice abstinence.
• Agrees that, with heterosexual intercourse with a fertile male partner, she will use an acceptable form of contraception and her male partner will use a condom with spermicide. Acceptable effective methods of female contraception include the following: bilateral tubal ligation, implant of levonorgestrel, injectable progestogen, intrauterine device oral contraceptive pills and diaphragm with spermicide.
• Willing to have samples stored for future research.
• HIV uninfected with a negative test within 60 days of Phase 2, Day 0.
• Agrees not to use IN medications (including but not limited to nasal
• sprays, sinus rinses), over-the-counter medications (including but not

You may not qualify if:

• Presence of self-reported or medically documented significant medical condition including but not limited to:
• Chronic pulmonary disease (e.g., asthma, emphysema).
• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
• Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
• Immunosuppression, immune deficiency (such as IgA deficiency) or ongoing malignancy.
• Neurological and neurodevelopmental conditions (e.g., Bell s palsy, cerebral palsy, epilepsy, stroke, seizures).
• Postinfectious or postvaccine neurological sequelae including Guillain Barre syndrome.
• Individual with body mass index less than or equal to 18 and greater than or equal to 40.
• Have close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:
• Persons greater than or equal to 65 years of age.
• Children less than or equal to 5 years of age.
• Residents of nursing homes.
• Persons of any age with significant chronic medical conditions such as:
• Chronic pulmonary disease (e.g., severe asthma, chronic obstructive pulmonary disease).
• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ainai A, Tamura S, Suzuki T, Ito R, Asanuma H, Tanimoto T, Gomi Y, Manabe S, Ishikawa T, Okuno Y, Odagiri T, Tashiro M, Sata T, Kurata T, Hasegawa H. Characterization of neutralizing antibodies in adults after intranasal vaccination with an inactivated influenza vaccine. J Med Virol. 2012 Feb;84(2):336-44. doi: 10.1002/jmv.22273.

  PMID: 22170556 BACKGROUND

• Gould VMW, Francis JN, Anderson KJ, Georges B, Cope AV, Tregoning JS. Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre. Front Microbiol. 2017 May 17;8:900. doi: 10.3389/fmicb.2017.00900. eCollection 2017.

  PMID: 28567036 BACKGROUND

• Flannery B, Chung JR, Belongia EA, McLean HQ, Gaglani M, Murthy K, Zimmerman RK, Nowalk MP, Jackson ML, Jackson LA, Monto AS, Martin ET, Foust A, Sessions W, Berman L, Barnes JR, Spencer S, Fry AM. Interim Estimates of 2017-18 Seasonal Influenza Vaccine Effectiveness - United States, February 2018. MMWR Morb Mortal Wkly Rep. 2018 Feb 16;67(6):180-185. doi: 10.15585/mmwr.mm6706a2.

  PMID: 29447141 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Matthew J Memoli, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2019
• First Posted: February 19, 2019
• Study Start: April 29, 2019
• Primary Completion: December 20, 2019
• Study Completion: October 28, 2020
• Last Updated: November 10, 2020

Record last verified: 2020-11-06

Locations

US (1)