TY - JOUR
T1 - Live respiratory syncytial virus (RSV) vaccine candidate containing stabilized temperature-sensitivity mutations is highly attenuated in RSV-seronegative infants and children
AU - Buchholz, Ursula J.
AU - Cunningham, Coleen K.
AU - Muresan, Petronella
AU - Gnanashanmugam, Devasena
AU - Sato, Paul
AU - Siberry, George K.
AU - Rexroad, Vivian
AU - Valentine, Megan
AU - Perlowski, Charlotte
AU - Schappell, Elizabeth
AU - Thumar, Bhagvinji
AU - Luongo, Cindy
AU - Barr, Emily
AU - Aziz, Mariam
AU - Yogev, Ram
AU - Spector, Stephen A.
AU - Collins, Peter L.
AU - McFarland, Elizabeth J.
AU - Karron, Ruth A.
N1 - Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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 10 5.3 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 log 10 PFU/mL by culture and 2.9 log 10 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.
AB - 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 10 5.3 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 log 10 PFU/mL by culture and 2.9 log 10 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.
KW - Pediatric vaccine
KW - Recombinant live-attenuated vaccine
KW - Respiratory syncytial virus
KW - Respiratory virus infection
KW - Reverse genetics
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U2 - 10.1093/infdis/jiy066
DO - 10.1093/infdis/jiy066
M3 - Article
C2 - 29509929
AN - SCOPUS:85050745387
SN - 0022-1899
VL - 217
SP - 1338
EP - 1346
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -