FORMULATION OF THE PURIFIED FUSION PROTEIN OF RESPIRATORY SYNCYTIAL VIRUS WITH THE SAPONIN QS-21 INDUCES PROTECTIVE IMMUNE-RESPONSES IN BALB C MICE THAT ARE SIMILAR TO THOSE GENERATED BY EXPERIMENTAL-INFECTION/

The feasibility of employing a vaccine composed of the purified fracti on 21 of Quillaja saponaria (QS-21) and the fusion (F) protein of resp iratory syncytial virus (RSV) to induce protective immune responses in the lower respiratory tract of Balb/c mice was examined. Our goal was to compare focal and systemic immune responses with those induced fol lowing immunization with the protein adsorbed to aluminium hydroxide ( F/ALOH) adjuvant or by experimental infection. Sera from mice vaccinat ed with the QS-21 formulation (F/QS-21) contained elevated anti-F prot ein IgG antibody titres that were dependent on the dose of QS-21 emplo yed. Similar to the immune responses generated by experimental infecti on, the sera from mice vaccinated with F/QS-21 possessed greater capac ity to neutralize virus infectivity that was associated with the gener ation of heightened complement-fixing IgG2a antibody titres. In contra st, vaccination with F/ALOH elicited systemic immune responses that we re characterized by a predominance of protein-specific antibodies of t he IgG1 subclass and lower neutralizing antibody titres. The capacity of F/QS-21 to facilitate local pulmonary immune responses was also exa mined and found to be similar to those induced by experimental infecti on. After virus challenge, a 90-fold increase in the number of F prote in-specific antibody-secreting cells was observed and associated with the clearance of virus from the infected lungs. Moreover, elevated lev els of antigen-dependent killer cell activity were detected and appear ed to be mediated by class I major histocompatibility complex restrict ed CD8+ T cells. Additional characterization of the pulmonary immune r esponse was performed on the cellular infiltrates obtained after bronc hoalveolar lavage and on formalin-fixed lung tissue. The local protect ive immune responses induced after challenge of the groups immunized w ith F/QS-21 Or infectious virus were significantly different from thos e elicited in naive control mice injected with adjuvant alone, or in m ice immunized with F/ALOH. The cellularity of the lavage fluids from t he former groups was characterized by a significantly greater percenta ge of lymphocytes and less neutrophils. In similar fashion histologica l evaluation of the lungs from mice immunized with F/QS-21 or infectio us virus revealed significantly elevated local immune responses after challenge. In conclusion, the results suggest that formulation with F/ QS-21 alters the qualitative and quantitative nature of the immune res ponse to the F glycoprotein when compared with the traditional alumini um-based adjuvants.