Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B.
The respiratory syncytial virus (RSV) is a serious pediatric pathogen for which there is currently no clinically approved vaccine. This report describes the design and testing of a new RSV vaccine construct (rSV-RSV-F), created by the recombination of an RSV F sequence with the murine parainfluenza virus-type 1 (Sendai virus, SV) genome. SV was selected as the vaccine backbone for this study, because it has previously been shown to elicit high-magnitude, durable immune activities in animal studies and has advanced to human safety trials as a xenogenic vaccine for human parainfluenza virus-type 1 (hPIV-1). Cells infected with the recombinant SV expressed RSV F protein, but F was not incorporated into progeny SV virions. When cotton rats were inoculated with the vaccine, high-titer RSV-binding and neutralizing antibodies as well as interferon-gamma-producing T-cells were induced. Most striking was the protection against intra-nasal RSV challenge conferred by the vaccine. The rSV-RSV-F construct was also tested as a mixture with a second SV construct expressing the RSV G protein, but no clear advantage was demonstrated by combining the two vaccines. As a final analysis, the efficacy of the rSV-RSV-F vaccine was tested against an array of RSV isolates. Results showed that neutralizing and protective responses were effective against RSV isolates of both A and B subtypes. Together, experimental results encourage promotion of this recombinant SV construct as a vaccine candidate for the prevention of RSV in humans.
Department of Infectious Diseases, St. Jude Children's Research Hospital, 332N. Lauderdale, Memphis, TN 38105, United States.
Xiaoyan
X
Zhan
Julia L
JL
Hurwitz
Sateesh
S
Krishnamurthy
Toru
T
Takimoto
Kelli
K
Boyd
Ruth A
RA
Scroggs
Sherri
S
Surman
Allen
A
Portner
Karen S
KS
Slobod
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000473:pathology / Q000821:virology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology*; D029082:Sendai virus / Q000235:genetics / Q000276:immunology*; D016205:Sigmodontinae; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; C116204:attachment protein G; D007371:Interferon-gamma