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.

Zhan X, Hurwitz JL, Krishnamurthy S, Takimoto T, Boyd K, Scroggs RA, Surman S, Portner A, Slobod KS
Vaccine. 2007 25 (52): 8782-93

PMID: 18037543 · PMCID: PMC2238687 · DOI:10.1016/j.vaccine.2007.10.038

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.

MeSH Terms (20)

Amino Acid Sequence Animals Antibodies, Viral Enzyme-Linked Immunosorbent Assay Female Humans Interferon-gamma Lung Molecular Sequence Data Neutralization Tests Respiratory Syncytial Viruses Respiratory Syncytial Virus Infections Sendai virus Sigmodontinae T-Lymphocytes Vaccines, Synthetic Viral Envelope Proteins Viral Fusion Proteins Viral Plaque Assay Viral Vaccines

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