THE PULMONARY IMMUNE-RESPONSE OF BALB C MICE VACCINATED WITH THE FUSION PROTEIN OF RESPIRATORY SYNCYTIAL VIRUS/

We have investigated the efficacy of vaccination with the purified fus ion (F) protein of respiratory syncytial virus (RSV) on aluminium hydr oxide adjuvant in Balb/c mice. The purpose of the study was to define the role of the local pulmonary mononuclear cell(PMC) infiltrate in th e clearance of virus from the lower respiratory tract. Balb/c mice imm unized with F protein were able to inhibit the replication of virus in the lungs as early as 4 days after intranasal challenge. In contrast, unimmunized mice required 8 days. Examination of humoral immune mecha nisms demonstrated that vaccination with the purified protein induced moderate titres of serum neutralizing antibody. In addition, immunizat ion induced low to moderate levels of antigen-dependent killer cell ac tivity. To examine the immunological events responsible for virus clea rance in vivo, PMC infiltrates were isolated after virus challenge and tested directly for protective capacity. After virus challenge, the F protein-immune mice were able to recall the cytolytic cells to the pu lmonary tissues. The results further suggested that the local antigen- dependent killer activity was mediated by cytolytic T cells of the CD8 phenotype. Adoptive transfer studies were also conducted to identify further the role the PMC infiltrate had in protective immunity. Adopti ve transfer of F protein-educated PMC into naive syngeneic recipients suggested that the pulmonary infiltrates contained the cellular consti tuents necessary for protective immunity. Both humoral and cellular im mune elements were present. Moreover, protection was observed in the a bsence of any overt morbidity. Thus the results suggested that vaccina tion with the F protein on aluminium hydroxide adjuvant induced the fo rmation of a local protective immune response in the lungs of Balb/c m ice that was not associated with heightened disease.