A subunit approach to the development of a respiratory syncytial virus (
RSV) vaccine was investigated. It involved the production, in Escherichia coli, of an RSV (Long)
G protein fragment (G2Na) as a C-terminal fusion partner to an
albumin binding region (BB) of
streptococcal protein G. G2Na incorporated
amino acid residues 130-230 and was specifically recognized by murine anti-RSV-A polyclonal serum. In mice, intraperitoneal immunization with
BBG2Na induced high anti-RSV-A serum ELISA titers and low to moderate neutralization activity. The immune response induced by
BBG2Na demonstrated a potent protective efficacy against upper and lower respiratory tract RSV-A
infection. The immunogenicity and protective efficacy of
BBG2Na was maintained for at least 47 and 48 weeks, respectively, and was as potent and durable as live RSV-A administered in a similar fashion. Intramuscular immunization of cotton rats with
BBG2Na protected lungs from both homologous and heterologous virus challenge. In contrast to mice, however, cotton rat nasal tracts were not protected after
BBG2Na immunization. Consistent with antibody-mediated protection, virus was cleared within 24 hr from the lungs of BBG2Na-immunized mice. The anti-RSV-A
antibodies induced in mice were exclusively of the
IgG1 isotype and were detected in the serum, lungs, and nasal tracts. Passive transfer of these
antibodies prevented acute, and eliminated chronic, RSV-A lung
infection in normal and immunodeficient mice, respectively, confirming that such
antibodies are important and sufficient for BBG2Na-induced pulmonary protection. Our results clearly demonstrate that
BBG2Na contains an important immunogenic domain of the RSV
G protein. The prokaryotic origin of this
protein indicates that glycosylation of the RSV
G protein is not necessary for protective efficacy. Thus,
BBG2Na has potential as an RSV
subunit vaccine.