Influence of administration dose and route on the immunogenicity and protective efficacy of BBG2Na, a recombinant respiratory syncytial virus subunitvaccine candidate

The immunogenicity and protective efficacy of BBG2Na, a novel recombinant r espiratory syncytial virus subunit vaccine candidate, was assessed in BALB/ c mice under various conditions of dose, administration route and number of immunisations. A single intra-peritoneal (i.p.) dose of 2 mu g, or two dos es of 0.2 mu g, were sufficient to induce elevated RSV-A serum antibodies a nd sterilising lung protective immunity. Serum antibody titres were signifi cantly boosted following second immunisations, but not a third. Of three ro utes of immunisation, i.p. induced the highest RSV-A antibody titres, follo wed in efficacy by the intramuscular (i.m.) and subcutaneous (s.c.) routes. Nonetheless, all three routes induced comparable and sterilising lung prot ection. In contrast, upper respiratory tract protection was observed only a fter i.p. vaccination, although significant viral titre reductions were evi dent following i.m. or s.c. immunisations. Interestingly, Pepscan analyses indicated that antibody epitope usage was highest in i.p. and lowest in i.m . immunised mice, respectively. Nonetheless, all routes resulted in antibod y responses to known lung protective epitopes (protectopes). Thus, the prev ention of serious lower respiratory tract disease, the principle goal of a RSV vaccine, but not URT infection, is dose dependent but unlikely to be in fluenced by the route of BBG2Na administration. (C) 2000 Elsevier Science L td. All rights reserved.