Sendai virus-based RSV vaccine protects against RSV challenge in an in vivo maternal antibody model.
Respiratory syncytial virus (RSV) is the cause of significant morbidity and mortality among infants, and despite decades of research there remains no licensed vaccine. SeVRSV is a Sendai virus (SeV)-based live intranasal vaccine that expresses the full length RSV fusion (F) gene. SeV is the murine counterpart of human parainfluenza virus type 1. Given that the target population of SeVRSV is young infants, we questioned whether maternal antibodies typical of this age group would inhibit SeVRSV vaccine efficacy. After measuring SeV- and RSV-specific serum neutralizing antibody titers in human infants, we matched these defined titers in cotton rats by the passive transfer of polyclonal or monoclonal antibody products. Animals were then vaccinated with SeVRSV followed by a 3 month rest period to allow passively transferred antibodies to wane. Animals were finally challenged with RSV to measure the de novo vaccine-induced immune responses. Despite the presence of passively-transferred serum neutralizing antibodies at the time of vaccination, SeVRSV induced immune responses that were protective against RSV challenge. The data encourage advancement of SeVRSV as a candidate vaccine for the protection of children from morbidity and mortality caused by RSV.
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA.
Bart G
BG
Jones
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA.
Robert E
RE
Sealy
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA.
Sherri L
SL
Surman
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA.
Allen
A
Portner
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
Charles J
CJ
Russell
Novartis Vaccines, Cambridge, MA, USA.
Karen S
KS
Slobod
Novartis Vaccines, Cambridge, MA, USA.
Philip R
PR
Dormitzer
Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA; Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TN, USA; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.
John
J
DeVincenzo
Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address: julia.hurwitz@stjude.org.
Julia L
JL
Hurwitz
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007116:Immunization, Passive; D007223:Infant; D007231:Infant, Newborn; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D022261:Respiratory Syncytial Virus Vaccines / Q000276:immunology*; D012136:Respiratory Syncytial Viruses; D029082:Sendai virus / Q000276:immunology*; D016205:Sigmodontinae
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022261:Respiratory Syncytial Virus Vaccines
Maternal antibody model; Neutralizing antibodies; Protective immunity; Respiratory syncytial virus vaccine; Sendai virus