PMID- 24204744
OWN - NLM
STAT- MEDLINE
DCOM- 20140826
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 10
DP  - 2013
TI  - Safety and immunogenicity of a live attenuated RSV vaccine in healthy 
      RSV-seronegative children 5 to 24 months of age.
PG  - e77104
LID - 10.1371/journal.pone.0077104 [doi]
LID - e77104
AB  - 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.
FAU - Malkin, Elissa
AU  - Malkin E
AD  - Clinical Development, MedImmune, Gaithersburg, Maryland, United States of 
      America.
FAU - Yogev, Ram
AU  - Yogev R
FAU - Abughali, Nazha
AU  - Abughali N
FAU - Sliman, Joseph
AU  - Sliman J
FAU - Wang, C Kathy
AU  - Wang CK
FAU - Zuo, Fengrong
AU  - Zuo F
FAU - Yang, Chin-Fen
AU  - Yang CF
FAU - Eickhoff, Mark
AU  - Eickhoff M
FAU - Esser, Mark T
AU  - Esser MT
FAU - Tang, Roderick S
AU  - Tang RS
FAU - Dubovsky, Filip
AU  - Dubovsky F
LA  - eng
SI  - ClinicalTrials.gov/NCT00767416
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20131029
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antibodies, Viral)
RN  - 0 (MEDI-559)
RN  - 0 (Respiratory Syncytial Virus Vaccines)
RN  - 0 (Vaccines, Attenuated)
SB  - IM
MH  - Antibodies, Viral/blood/*immunology
MH  - Child, Preschool
MH  - Cohort Studies
MH  - Cough/chemically induced
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Nasal Obstruction/chemically induced
MH  - Respiratory Syncytial Virus Infections/blood/*immunology/prevention & control
MH  - Respiratory Syncytial Virus Vaccines/administration & dosage/adverse 
      effects/*immunology
MH  - Respiratory Syncytial Viruses/*immunology
MH  - Time Factors
MH  - Treatment Outcome
MH  - Vaccination/methods
MH  - Vaccines, Attenuated/administration & dosage/adverse effects/immunology
PMC - PMC3812203
COIS- 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.
EDAT- 2013/11/10 06:00
MHDA- 2014/08/27 06:00
PMCR- 2013/10/29
CRDT- 2013/11/09 06:00
PHST- 2013/05/21 00:00 [received]
PHST- 2013/08/28 00:00 [accepted]
PHST- 2013/11/09 06:00 [entrez]
PHST- 2013/11/10 06:00 [pubmed]
PHST- 2014/08/27 06:00 [medline]
PHST- 2013/10/29 00:00 [pmc-release]
AID - PONE-D-13-21547 [pii]
AID - 10.1371/journal.pone.0077104 [doi]
PST - epublish
SO  - PLoS One. 2013 Oct 29;8(10):e77104. doi: 10.1371/journal.pone.0077104. 
      eCollection 2013.