Study to Evaluate the Safety of 1 New 6:2 Influenza Virus Reassortant in Adults for the 2017-2018 Season

This prospective annual release study is designed to evaluate the safety of 1 new influenza virus vaccine strain to be included in FluMist Quadrivalent for the 2017-2018 influenza season.

This prospective, randomized, double-blind, placebo-controlled release study will enroll approximately 300 healthy adults 18 to 49 years of age (not yet reached their 50th birthday). Eligible participants will be randomly assigned in a 4:1 fashion to receive a single dose of monovalent vaccine or placebo by intranasal spray. Randomization will be stratified by site. This study will be conducted at 2 sites in the United States of America. Each participant will receive 1 dose of investigational product on Day 1. The duration of study participation for each participant is the time from study vaccination through 180 days after study vaccination.

Eligibility Criteria:
Key Inclusion Criteria:

* Age 18 through 49 years
* Written informed consent
* Participant available by telephone
* Ability to understand and comply with the requirements of the protocol, as judged by the Investigator

Key Exclusion Criteria:

* Concurrent enrollment in another clinical study up to 180 days after receipt of investigational product (Day 181)
* History of hypersensitivity to any component of the vaccine, including egg or egg protein or serious, life threatening, or severe reactions to previous influenza vaccinations
* Any condition for which the inactivated influenza vaccine is indicated, including chronic disorders of the pulmonary or cardiovascular systems (example \[eg\], asthma), chronic metabolic diseases (eg, diabetes mellitus), renal dysfunction, or hemoglobinopathies that required regular medical follow-up or hospitalization during the preceding year
* Acute febrile (greater than \[\>\] 100.0 degrees Fahrenheit \[F\] oral or equivalent) and/or clinically significant respiratory illness (example, cough or sore throat) within 14 days to randomization
* Any known immunosuppressive condition or immune deficiency diseases, including human immunodeficiency virus infection, or ongoing immunosuppressive therapy
* History of Guillain-Barre syndrome
* Receipt of any investigational agent within 30 days prior to randomization, or expected receipt through 30 days after the dose of investigational product (use of licensed agents for indications not listed in the Package Insert is permitted)
* Receipt of any non-study vaccine within 30 days prior to randomization, or expected receipt through 30 days after receipt of investigational product
* Expected receipt of antipyretic or analgesic medication on a daily or every other day basis from randomization through 14 days after receipt of investigational product
* Administration of intranasal medications within 14 days prior to randomization, or expected receipt through 14 days after administration of investigational product
* Receipt of influenza antiviral therapy or influenza antiviral agents within 48 hours prior to investigational product administration or expected receipt of influenza antiviral therapy or influenza antiviral agents through 14 days after receipt of investigational product