Evaluating the Infectivity, Safety, and Immunogenicity of Recombinant Live-Attenuated RSV Vaccines RSV ΔNS2/Δ1313/I1314L or RSV 276 in RSV-Seronegative Infants 6 to 24 Months of Age

Inclusion Criteria

• In good health based on review of the medical record, history, and physical examination, without evidence of chronic disease.
• Parent/guardian willing and able to provide written informed consent as described in the protocol.
• Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening from a sample collected no more than 42 days prior to inoculation.
• Growing normally for age (i.e., not downwardly crossing two major centiles on a standard growth chart) in the six months prior to enrollment AND
• If less than 1 year of age: current height and weight above the 5th percentile
• If 1 year of age or older: current height and weight above the 3rd percentile for age.
• Received routine immunizations appropriate for age (as per national Center for Disease Control Advisory Committee on Immunization Practices).
• Expected to be available for the duration of the study.
• If born to an HIV-infected woman, participant must not have been breastfed and must have documentation of 2 negative HIV nucleic acid (RNA or DNA) test results from samples collected on different dates with both collected when greater than or equal to 4 weeks of age and at least one collected when greater than or equal to 16 weeks of age, and no positive HIV nucleic acid (RNA or DNA) test; or 2 negative HIV antibody tests, both from samples collected at greater than or equal to 24 weeks of age.

Exclusion Criteria

• Known or suspected HIV infection or impairment of immunological functions.
• Receipt of immunosuppressive therapy, including any systemic, including either nasal or inhaled, corticosteroids within 28 days of enrollment. Note: Cutaneous (topical) steroid treatment is not an exclusion.
• Any receipt of bone marrow/solid organ transplant.
• Major congenital malformations (such as congenital cleft palate) or cytogenetic abnormalities.
• Previous receipt of a licensed or investigational RSV vaccine (or placebo in any International Maternal Pediatric Adolescent AIDS Clinical Trials Network RSV study) or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV IG or RSV mAb).
• Any previous anaphylactic reaction.
• Any previous vaccine-associated adverse reaction that was Grade 3 or above. Note: if grading is not possible, determine if the reaction was considered severe or life threatening; if so, it is exclusionary.
• Any known hypersensitivity to any study product component.
• Heart disease. Note: Participants with cardiac abnormalities documented to be clinically insignificant and requiring no treatment may be enrolled.
• Lung disease, including any history of reactive airway disease or medically diagnosed wheezing.
• Member of a household that contained, or would contain, an infant who is less than 6 months of age at the enrollment date through Day 28.
• Member of a household that contained another child/other children who was/were, or was/were scheduled to be, enrolled in IMPAACT 2018 AND the date of enrollment to IMPAACT 2018 would not be concurrent with the other participant(s) living in the household (i.e., all eligible children from the same household must be enrolled on the same date).
• Member of a household that contained another child who was, or was scheduled to be, enrolled in another study evaluating an intranasal live-attenuated RSV vaccine, AND there has been or would be an overlap in residency during that other child's participation in the study's Acute Phase (Days 0 to 28).
• Member of a household that contained an immunocompromised individual, including, but not limited to:
• a person who was greater than or equal to 6 years of age with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell count less than 300 cells/mm^3. CD4 T lymphocyte count must have been measured within 6 months prior to enrollment for individuals with detectable virus or within 12 months prior to enrollment for individuals wit