Human antibody responses to mature and immature forms of viral envelope inrespiratory syncytial virus infection: Significance for subunit vaccines

A number of antibodies generated during human respiratory syncytial virus ( RSV) infection have been cloned by the phage library approach. Antibodies r eactive with an immunodominant epitope on the F glycoprotein of this virus have a high affinity for affinity-purified F antigen. These antibodies, how ever, have a much lower affinity for mature F glycoprotein on the surface o f infected cells and are nonneutralizing. In contrast, a patent neutralizin g antibody has a high affinity for mature F protein but a much lower affini ty for purified F protein or F protein in viral lysates. The data indicate that at least two F protein immunogens are produced during natural RSV infe ction: immature F, found in viral lysates, and mature F, found on infected cells or virions. Binding studies with polyclonal human immunoglobulin G su ggest that the antibody responses to the two immunogens are of similar magn itudes. Competitive binding studies suggest that overlap between the respon ses is relatively limited. A mature envelope with an antigenic configuratio n different from that of the immature envelope has an evolutionary advantag e in that the infecting virus is less subject to neutralization by the humo ral response to the immature envelope that inevitably arises following lysi s of infected cells. Subunit vaccines may be at a disadvantage because they most often resemble immature envelope molecules and ignore this aspect of viral evasion.