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

  • End date
    Mar 19, 2022
  • participants needed
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 15 November 2020
Rani S Athota, Ph.D.
Primary Contact
National Institutes of Health Clinical Center (9.7 mi away) Contact
tubal ligation
nasal spray
influenza vaccination
viral shedding
flu symptoms



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.


To compare the body s ability to fight infection when a flu vaccine is given in the nose versus the arm.


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.


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.


The high morbidity and mortality associated with both pandemic and seasonal influenza and the threat of new potentially pandemic strains emerging makes influenza an important infectious disease and public health problem. Public health agencies must continue attempts to reduce the public health impact of this important virus.

Currently, influenza vaccination is the cornerstone of prophylaxis and the most effective method available to reduce the impact of influenza on the population. Current vaccines target the major surface protein, hemagglutinin (HA), and are standardized by stimulation of serum anti-HA antibodies as the primary correlate of protection. Measurements of serum antibodies to HA have become the gold standard for evaluating vaccines. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) both define protective titers as a hemagglutination inhibition (HAI) titer of greater than or equal to 40. Recent vaccine effectiveness has been limited and, in some populations, estimated at as low as 10%. Improved methods of vaccination must be developed, but limited information regarding the true correlates of protection is available. Correlates of protection in the systemic circulation may be less informative than those located in the nasopharyngeal mucosa, which is the site of exposure to and infection with influenza virus.

This study is designed to characterize the mucosal and systemic immunologic correlates of protection from influenza infection in persons vaccinated and unvaccinated against influenza. Half of participants will receive current licensed quadrivalent inactivated influenza vaccine (IIV) administered via the intramuscular (IM) route at the standard dose, prior to challenge with influenza virus. The other half will receive no vaccination prior to challenge. Immunologic response and clinical outcomes in the human challenge model will be determined to characterize the two cohorts. In the vaccinated cohort, mucosal and systemic immune responses induced by IM administration of quadrivalent IIV will also be carefully explored. The thoughtful study of mucosal immunity to influenza is expected to identify novel correlates of protection. By administering quadrivalent IIV and then infecting participants with human challenge virus, we can evaluate in detail the immunologic responses after immunization and subsequent virus exposure. This controlled setting offers the ideal environment to query these responses and to identify targets of mucosal stimulation for future vaccine strategies. In addition, the detailed characterization of the mucosal and systemic immune responses after vaccination and challenge will represent a true advance in understanding influenza immunity.

Treatment FluCelVax, Human Challenge virus
Clinical Study IdentifierNCT03845231
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on15 November 2020

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