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Randomized Controlled Trial
. 2013 Oct 29;8(10):e77104.
doi: 10.1371/journal.pone.0077104. eCollection 2013.

Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age

Elissa Malkin  1 , Ram Yogev, Nazha Abughali, Joseph Sliman, C Kathy Wang, Fengrong Zuo, Chin-Fen Yang, Mark Eickhoff, Mark T Esser, Roderick S Tang, Filip Dubovsky
Affiliations
Randomized Controlled Trial

Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age

Elissa Malkin et al. PLoS One. .

Abstract

Despite substantial morbidity associated with respiratory syncytial virus (RSV) infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs) and adverse events (AEs) collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34) and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%); most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%). Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding). There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory illnesses in the vaccine group warrants expanded safety studies.

Trial registration: ClinicalTrials.gov NCT00767416.

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Conflict of interest statement

Competing Interests: Elissa Malkin, Joseph Sliman, Roderick Tang, and Chin-Fen Yang were employees of MedImmune during the conduct of the study. Mark Eickhoff, Mark Esser, Kathy Wang, Fengrong Zuo, and Filip Dubovsky are employees of MedImmune and receive stock/stock options from AstraZeneca. Ram Yogev received research funding from MedImmune for the conduct of the study and has been paid for lectures, including service on the Speakers Bureau for MedImmune. Nazha Abughali received research funding from MedImmune for the conduct of the study. All authors confirm that this does not alter their adherence to all PLOS ONE policies on sharing data and materials. MedImmune funded the study and was involved in the study design, data collection and analysis, decision to publish, and preparation of the manuscript.

Figures

Figure 1
Figure 1. Subject disposition (CONSORT flowchart).
Figure 2
Figure 2. Proportion of MEDI-559 recipients who shed vaccine-type virus, stratified by study visit.
See this image and copyright information in PMC

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