Correlates of Immunity to Influenza as Determined by Challenge of Children with Live, Attenuated Influenza Vaccine

Autor: John J. Treanor, Margaret E. Ackerman, Eric P. Brown, Wendy Wieland-Alter, Peter F. Wright, Catherine J. Luke, Natalia A. Ilyushina, Yael Rosenberg-Hasson, Ruth I. Connor, Sinthujan Jegaskanda, Anne G. Hoen, Kanta Subbarao, Brenda C. Haynes
Rok vydání: 2016
Předmět:
Zdroj: Open Forum Infectious Diseases
ISSN: 2328-8957
Popis: There are 2 distinct approaches to the prevention of influenzal illness. Live, attenuated influenza vaccines (LAIVs) are reassortants between internal protein genes from attenuated master strains and contemporary wild-type hemagglutinin (HA) and neuraminidase (NA) genes representing circulating influenza viruses. Live, attenuated influenza vaccines are delivered by large-particle aerosol spray into the upper respiratory tract where they replicate and mimic many aspects of the pathogenesis of wild-type influenza infection. Inactivated influenza vaccines (IIVs) are given intramuscularly and contain purified, inactivated, and structurally disrupted virus particles enriched for HA and NA and standardized to HA content. The use of LAIV as an experimental challenge to predict protection against subsequent infection afforded by different approaches to vaccination has been reported for both polio and influenza [1–3]. An earlier paper by our group demonstrated decreased shedding in children immunized with seasonal LAIV, compared with IIV, following challenge with LAIV 1 month after the initial vaccination [4]. In children challenged with LAIV after IIV, 10 of 15 shed 1 or more of the influenza virus strains in the trivalent vaccine with 21 of 45 possible strains recovered. In contrast, when LAIV recipients were challenged with LAIV, 1 of 11 shed virus—although that child shed all 3 strains after both vaccinations. The current study included quantitative, strain-specific virus shedding and multiple measurements of mucosal and systemic immunity at the time of, and after, each vaccine dose. Data from this study allowed us to examine the following: (1) correlations between measurements of systemic and mucosal immunity, (2) patterns of immunity induced by LAIV and IIV, and (3) correlates of protection upon LAIV challenge. With the limitations of a relatively small sample size and the short duration between vaccination and challenge, we demonstrated different patterns of immunity induced by the 2 vaccines. However, none of the standard measures of either systemic or mucosal immunity predicted the comparative efficacy of the 2 vaccines in limiting virus shedding on subsequent LAIV challenge.
Databáze: OpenAIRE