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J Infect Dis. 2018 Apr 11;217(9):1338-1346. doi: 10.1093/infdis/jiy066.

Live Respiratory Syncytial Virus (RSV) Vaccine Candidate Containing Stabilized Temperature-Sensitivity Mutations Is Highly Attenuated in RSV-Seronegative Infants and Children.

Author information

1
RNA Viruses Section, Laboratory of Infectious Diseases, Bethesda.
2
Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina.
3
Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
4
Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda.
5
Maternal Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda.
6
Johns Hopkins Hospital.
7
FHI 360, Durham, North Carolina.
8
Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
9
Department of Pediatric Infectious Diseases, Aurora, Colorado.
10
Mucosal and Vaccine Research Program Colorado, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
11
Rush University Medical Center, Chicago, Illinois.
12
Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
13
Clinical Trials Unit, International Maternal Pediatric Adolescent AIDS Clinical Trials Group, University of California, San Diego, California.

Abstract

Background:

Respiratory syncytial virus (RSV) is the most important viral cause of severe respiratory illness in young children and lacks a vaccine. RSV cold-passage/stabilized 2 (RSVcps2) is a modification of a previously evaluated vaccine candidate in which 2 major attenuating mutations have been stabilized against deattenuation.

Methods:

RSV-seronegative 6-24-month-old children received an intranasal dose of 105.3 plaque-forming units (PFU) of RSVcps2 (n = 34) or placebo (n = 16) (International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1114 and companion protocol CIR285). RSV serum neutralizing antibody titers before and 56 days after vaccination, vaccine virus infectivity (defined as vaccine virus shedding detectable in nasal wash and/or a ≥4-fold rise in serum antibodies), reactogenicity, and genetic stability were assessed. During the following RSV transmission season, participants were monitored for respiratory illness, with serum antibody titers measured before and after the season.

Results:

A total of 85% of vaccinees were infected with RSVcps2 (median peak titer, 0.5 log10 PFU/mL by culture and 2.9 log10 copies/mL by polymerase chain reaction analysis); 77% shed vaccine virus, and 59% developed a ≥4-fold rise in RSV-serum neutralizing antibody titers. Respiratory tract and/or febrile illness occurred at the same rate (50%) in the vaccine and placebo groups. Deattenuation was not detected at either of 2 stabilized mutation sites.

Conclusions:

RSVcps2 was well tolerated and moderately immunogenic and had increased genetic stability in 6-24-month-old RSV-seronegative children.

Clinical Trials Registration:

NCT01852266 and NCT01968083.

PMID:
29509929
PMCID:
PMC5894088
DOI:
10.1093/infdis/jiy066
[Indexed for MEDLINE]
Free PMC Article

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