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

Kristen D.C. Lewis, Justin R. Ortiz, Mohammed Z. Rahman, Min Z. Levine, Larisa Rudenko, Peter F. Wright, Jacqueline M. Katz, Len Dally, Mustafizur Rahman, Irina Isakova-Sivak, Natalia A. Ilyushina, Victoria Matyushenko, Alicia M. Fry, Stephen E. Lindstrom, Joseph S. Bresee, W Abdullah Brooks, Kathleen M. Neuzil

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numberciy1003
Pages (from-to)777-785
Number of pages9
JournalClinical Infectious Diseases
Volume69
Issue number5
DOIs
StatePublished - Aug 16 2019

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Virus Shedding
Bangladesh
Influenza Vaccines
Preschool Children
Attenuated Vaccines
Randomized Controlled Trials
Placebos
Immunoglobulin A
Vaccines
Immunoassay
Enzyme-Linked Immunosorbent Assay
H1N1 Subtype Influenza A Virus
Hemagglutination
Reverse Transcription
Antibody Formation
Immunoglobulin G
Clinical Trials
Polymerase Chain Reaction
Serum
Research

Keywords

  • Bangladesh
  • children
  • clinical trials
  • influenza vaccine

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

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. / Lewis, Kristen D.C.; Ortiz, Justin R.; Rahman, Mohammed Z.; Levine, Min Z.; Rudenko, Larisa; Wright, Peter F.; Katz, Jacqueline M.; Dally, Len; Rahman, Mustafizur; Isakova-Sivak, Irina; Ilyushina, Natalia A.; Matyushenko, Victoria; Fry, Alicia M.; Lindstrom, Stephen E.; Bresee, Joseph S.; Brooks, W Abdullah; Neuzil, Kathleen M.

In: Clinical Infectious Diseases, Vol. 69, No. 5, ciy1003, 16.08.2019, p. 777-785.

Research output: Contribution to journalArticle

Lewis, KDC, Ortiz, JR, Rahman, MZ, Levine, MZ, Rudenko, L, Wright, PF, Katz, JM, Dally, L, Rahman, M, Isakova-Sivak, I, Ilyushina, NA, Matyushenko, V, Fry, AM, Lindstrom, SE, Bresee, JS, Brooks, WA & Neuzil, KM 2019, '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', Clinical Infectious Diseases, vol. 69, no. 5, ciy1003, pp. 777-785. https://doi.org/10.1093/cid/ciy1003
Lewis, Kristen D.C. ; Ortiz, Justin R. ; Rahman, Mohammed Z. ; Levine, Min Z. ; Rudenko, Larisa ; Wright, Peter F. ; Katz, Jacqueline M. ; Dally, Len ; Rahman, Mustafizur ; Isakova-Sivak, Irina ; Ilyushina, Natalia A. ; Matyushenko, Victoria ; Fry, Alicia M. ; Lindstrom, Stephen E. ; Bresee, Joseph S. ; Brooks, W Abdullah ; Neuzil, Kathleen M. / 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. In: Clinical Infectious Diseases. 2019 ; Vol. 69, No. 5. pp. 777-785.
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abstract = "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.",
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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.

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

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