Elsevier

The Journal of Pediatrics

Volume 136, Issue 2, February 2000, Pages 168-175
The Journal of Pediatrics

Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine,☆☆,

https://doi.org/10.1016/S0022-3476(00)70097-7Get rights and content

Abstract

Objective: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. Study design: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. Results: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. Conclusions: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza. (J Pediatr 2000;136:168-75)

Section snippets

Vaccine and Placebo

Trivalent cold-adapted influenza vaccine was supplied by Aviron (Mountain View, Calif), frozen in single-dose intranasal applicators described below. In year 1, the vaccine contained 106.7 median tissue culture infective doses per dose, and in year 2, reported here, the vaccine contained 107.0 median tissue culture infective doses per dose of each of the 3 attenuated strains that matched the antigens as recommended for the trivalent inactivated influenza vaccine by the Food and Drug

RESULTS

The results of year 1 of this efficacy field trial have been reported previously.14 For context, the efficacy results from year 1 are summarized in Table I along with year 2 results. In September of 1997, 1358 of the original study group of 1602 children (85%) were revaccinated with a single dose of live attenuated influenza vaccine or placebo by nasal spray. There were no statistically significant differences between age, sex, race, day-care enrollment, or household compositions of vaccine and

DISCUSSION

Live attenuated influenza vaccine provided high efficacy, 92%, over 2 years against culture-confirmed influenza. This interval included a year in which the influenza strains selected for inclusion in the vaccine did not closely match the circulating predominant strain, influenza A/Sydney/5/97. Influenza A/Sydney/5/97 was found to be significantly different from influenza A/Nanchang/933/95 (an influenza A/Wuhan/359/95–like virus) when tested by ferret antisera.19 The late emergence of influenza

Acknowledgements

We thank the clinic coordinators, referring pediatricians, and parents who assisted with this study. Study personnel contributing to this study include Joan Cannon, Frances Newman, Peter Wright, Judi Thompson, Sharon Tollefson, Jane Baker, Thomas Boyce, Edie Sannella, Shanita Coleman-Dockery, Elizabeth Budd, Annamay Zindahl, Marty Spalding, William Blackwelder, Connie Turner, Kirti Patel, Mike Pichichero, Diane O’Brien, Rosalyn Battaglia, Bernard Readmond, Eliza Sindall, Debra Campbell, Susan

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  • Cited by (0)

    Supported by the National Institutes of Health, Bethesda, Maryland, and Aviron, Mountain View, California.

    ☆☆

    Reprint requests: Robert B. Belshe, MD, Saint Louis University Health Sciences Center, Division of Infectious Diseases, 3635 Vista Ave, FDT-8N, St Louis, MO 63110.

    0022-3476/2000/$12.00 + 0  9/21/102916

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