TY - JOUR
T1 - Live-attenuated respiratory syncytial virus vaccine with deletion of RNA synthesis regulatory protein M2-2 and cold passage mutations is overattenuated
AU - Cunningham, Coleen K.
AU - Karron, Ruth
AU - Muresan, Petronella
AU - McFarland, Elizabeth J.
AU - Perlowski, Charlotte
AU - Libous, Jennifer
AU - Thumar, Bhagvanji
AU - Gnanashanmugam, Devasena
AU - Moye, Jack
AU - Schappell, Elizabeth
AU - Barr, Emily
AU - Rexroad, Vivian
AU - Aziz, Mariam
AU - Deville, Jaime
AU - Rutstein, Richard
AU - Yang, Lijuan
AU - Luongo, Cindy
AU - Collins, Peter
AU - Buchholz, Ursula
N1 - Funding Information:
Financial support. This work was supported by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, funded by the National Institute of Allergy and Infectious Diseases (NIAID) with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH), all components of the National Institutes of Health (NIH; UM1AI068632 [IMPAACT LOC], UM1AI068616 [IMPAACT SDMC], and UM1AI106716 [IMPAACT LC]), and by the NICHD (HHSN275201800001I). R.A.K., B.T., and E.S. were supported by NIAID contract (HHSN272200900010C). This work also received support from Sanofi Pasteur Inc. through a Cooperative Research And Development Agreement (CRADA) with the NIAID. L.Y., C.L., P.L.C., and U.J.B. were supported by the Intramural Program of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. This publication resulted in part from research supported by the Duke University Center for AIDS Research (CFAR), an NIH-funded program (5P30 AI064518), to C.K.C. and the Colorado Clinical and Translational Science Award (CTSA) from the National Center for Advancing Translational Science (NCATS; UL1 TR001082) to E.J.M.
Publisher Copyright:
© The Author(s) 2019.
PY - 2019/6/3
Y1 - 2019/6/3
N2 - Background. The live respiratory syncytial virus (RSV) candidate vaccine LIDcpδM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. Methods. RSV-seronegative children aged 6-24 months received a single intranasal dose of 105 plaque-forming units (PFU) of LIDcpδM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. Results. Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log10 PFU/mL by quantitative culture and 4.5 log10 copies/mL by polymerase chain reaction; 45% had =4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%).
AB - Background. The live respiratory syncytial virus (RSV) candidate vaccine LIDcpδM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations. Methods. RSV-seronegative children aged 6-24 months received a single intranasal dose of 105 plaque-forming units (PFU) of LIDcpδM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed. Results. Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log10 PFU/mL by quantitative culture and 4.5 log10 copies/mL by polymerase chain reaction; 45% had =4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%).
KW - Immunogenicity
KW - Live-attenuated viral vaccine
KW - Neutralizing antibodies
KW - Pediatric RSV vaccine
KW - RNA regulatory protein M2-2
KW - Respiratory syncytial virus
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U2 - 10.1093/ofid/ofz212
DO - 10.1093/ofid/ofz212
M3 - Article
C2 - 31211158
AN - SCOPUS:85068513984
SN - 2328-8957
VL - 6
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 6
M1 - ofz212
ER -