TY - JOUR
T1 - 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
AU - Lewis, Kristen D.C.
AU - Ortiz, Justin R.
AU - Rahman, Mohammed Z.
AU - Levine, Min Z.
AU - Rudenko, Larisa
AU - Wright, Peter F.
AU - Katz, Jacqueline M.
AU - Dally, Len
AU - Rahman, Mustafizur
AU - Isakova-Sivak, Irina
AU - Ilyushina, Natalia A.
AU - Matyushenko, Victoria
AU - Fry, Alicia M.
AU - Lindstrom, Stephen E.
AU - Bresee, Joseph S.
AU - Brooks, W. Abdullah
AU - Neuzil, Kathleen M.
N1 - Funding Information:
This work was supported by funding from the Bill & Melinda Gates Foundation, which provides financial support to PATH's Influenza Vaccine Project (grant number OPP48805). Serum Institute of India, Ltd., donated the study vaccine and placebo.
Funding Information:
Financial support. This work was supported by funding from the Bill & Melinda Gates Foundation, which provides financial support to PATH’s Influenza Vaccine Project (grant number OPP48805). Serum Institute of India, Ltd., donated the study vaccine and placebo. Potential conflicts of interest. J. R. O., K. M. N., M. Z. R., and M. R. report a grant from the Centers for Disease Control and Prevention. J. M. K. has 2 patents issued: “Preparation and use of recombinant influenza A virus M2 construct vaccine” and “An effective vaccine against pandemic strains of influenza viruses.” All other authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Publisher Copyright:
© 2018 The Author(s) 2018.
PY - 2019/8/16
Y1 - 2019/8/16
N2 - Background: 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. Clinical Trials Registration: NCT01625689.
AB - Background: 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. Clinical Trials Registration: NCT01625689.
KW - Bangladesh
KW - children
KW - clinical trials
KW - influenza vaccine
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U2 - 10.1093/cid/ciy1003
DO - 10.1093/cid/ciy1003
M3 - Article
C2 - 30481272
AN - SCOPUS:85069633537
SN - 1058-4838
VL - 69
SP - 777
EP - 785
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 5
M1 - ciy1003
ER -