Immunogenicity and Viral Shedding of Russian-Backbone, Seasonal, Trivalent, Live, Attenuated Influenza Vaccine in a Phase II, Randomized, Placebo-Controlled Trial among Preschool-Aged Children in Urban Bangladesh
JournalClinical Infectious Diseases
PublisherOxford University Press
MetadataShow full item record
AbstractBackground: We evaluated a Russian-backbone, live, attenuated influenza vaccine (LAIV) for immunogenicity and viral shedding in a randomized, placebo-controlled trial among Bangladeshi children. Methods: Healthy children received a single, intranasal dose of LAIV containing the 2011–2012 recommended formulation or placebo. Nasopharyngeal wash (NPW) specimens were collected on days 0, 2, 4, and 7. Reverse transcription polymerase chain reactions and sequencing identified the influenza virus (vaccine or wild-type). On days 0 and 21, blood specimens were collected to assess immunogenicity using hemagglutination inhibition, microneutralization, and immunoglobulin A (IgA) and G enzyme-linked immunosorbent assays (ELISAs); NPW specimens were also collected to assess mucosal immunogenicity using kinetic IgA ELISA. Results: We enrolled 300 children aged 24 through 59 months in the immunogenicity and viral shedding analyses. Among children receiving LAIV, 45% and 67% shed A/H3N2 and B vaccine strains, respectively. No child shed A/H1N1 vaccine strain. There were significantly higher day 21 geometric mean titers (GMTs) for the LAIV, as compared to the placebo groups, in all immunoassays for A/H3N2 and B (log10 titer P < .0001; GMT Ratio >2.0). Among immunoassays for A/H1N1, only the mucosal IgA GMT was significantly higher than placebo at day 21 (log10 titer P = .0465). Conclusions: Children vaccinated with LAIV had serum and mucosal antibody responses to A/H3N2 and B, but only a mucosal IgA response to A/H1N1. Many children shed A/H3N2 and B vaccine strains, but none shed A/H1N1. More research is needed to determine the reason for decreased LAIV A/H1N1 immunogenicity and virus shedding.
SponsorsThis study was approved by the icddr,b (Dhaka, Bangladesh), the Western Institutional Review Boards (Olympia, WA), the Committee for the Protection of Human Subjects at Dartmouth College (Hanover, NH), and CDC Human Subject Research Determination Review. The trial followed International Conference on Harmonization Good Clinical Practice guidelines and was registered with ClinicalTrials.gov (NCT01625689).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85069633537&doi=10.1093%2fcid%2fciy1003&partnerID=40&md5=f1ff09d4834ddba38008990b5dc617e7; http://hdl.handle.net/10713/10522
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