Mutant forms of the F protein of human respiratory syncytial (RS) virus induce a cytotoxic T lymphocyte response but not a neutralizing antibody response and only transient resistance to RS virus infection

Abstract

Vaccinia virus (vv) recombinants expressing either wild-type (VA-F) or mutant forms (VA-FT, VA-FR47, VA-FS1 to VA-FS6) of the fusion (F) protein of respiratory syncytial (RS) virus were examined for their ability to elicit antibody, cytotoxic T lymphocytes (CTL) and protection against RS virus infection in BALB/c mice. Cells infected with the VA-F and VA-FT recombinants expressed the F protein on their surface and mice vaccinated with these recombinants developed RS virus neutralizing antibodies. The VA-FR47 recombinant expressed a mutant form of the F protein (with six amino acid changes from the wild-type) in which both proteolytic processing of the F0 precursor and its transport to the cell surface were inhibited. These mutants induced transient protection against RS virus infection although they did not induce RS virus neutralizing antibodies, or antibodies detectable by ELISA. All the vv recombinants were able to induce an RS virus-specific, MHC class I restricted CTL response. Vaccination of mice with a second set of vv recombinants expressing mutant forms of the F protein showed that the replacement Phe to Ser at amino acid 237 either alone or in combination with others abolished the neutralizing antibody response but did not affect priming of CTLs. These results demonstrate that long-term protection against RS virus infection in mice vaccinated with recombinant vv expressing the F protein is more dependent upon the induction of an antibody rather than a CTL response.