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Clinical Trial
. 2019 Aug 16;69(5):777-785.
doi: 10.1093/cid/ciy1003.

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  1 , Justin R Ortiz  2 , Mohammed Z Rahman  3 , Min Z Levine  4 , Larisa Rudenko  5 , Peter F Wright  6 , Jacqueline M Katz  4 , Len Dally  7 , Mustafizur Rahman  3 , Irina Isakova-Sivak  5 , Natalia A Ilyushina  8 , Victoria Matyushenko  5 , Alicia M Fry  4 , Stephen E Lindstrom  4 , Joseph S Bresee  4 , W Abdullah Brooks  9 , Kathleen M Neuzil  2
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Clinical Trial

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 et al. Clin Infect Dis. .

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.

Keywords: Bangladesh; children; clinical trials; influenza vaccine.

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Figures

Figure 1.
Figure 1.
Participant flow. Abbreviation: LAIV, live, attenuated influenza vaccine. a1 specimen not collected and 1 invalid result. bExclusions due to invalid results.
Figure 2.
Figure 2.
Post-vaccination 4-fold rises, by assays and influenza vaccine strains. All data points shown are the proportion (%) out of 150. Risk difference is defined as the difference between LAIV and the placebo. Abbreviations: HAI, hemagglutination inhibition assay; IgA, immunoglobulin A assay; IgG, immunoglobulin G assay; LAIV, live, attenuated influenza vaccine; MN, microneutralization assay.
Table 3.
Table 3.
Correlations Among Post-Vaccination Immunoassays Achieving 4-Fold Rise in Titer and Any Vaccine Virus Detections in LAIV Recipients Aged 24 Through 59 Months
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