Study On The Preparation Of RSV Recombinant Protein Vaccine And Evaluation Its Immunogenicity And Protective Efficacy

Respiratory syncytial virus (RSV), an important pathogen of the lower respiratory tract, is responsible for severe illness both in new born and young children and in elderly people. Early studies in the 1960s showed that children vaccinated with a formalin-inactivated RSV(FI-RSV) vaccine suffered from more severe disease on subsequent exposure to the virus as compared to unvaccinated controls. These early trials resulted in the hospitalization of 80% of vaccinees and two deaths. The enhanced severity of disease is thought to result from excessive induction of a type 2 helper T-cell like (Th2) immune response with pulmonary eosinophilia and increased production of IL-4 and IL-5 cytokines, inadequate levels of serum neutralizing antibodies, lack of local immunity and immune complex deposition.Previous studies in mice indicated that G protein immunization resulted in IgG1 antibody and Th2-type response and failed to induce IgG2a, Th1 and MHC I-restricted CD8~+T cell response. Eosinophilia in mice can be prevented along with down regulation of pulmonary Th2 cytokines if RSV-specific CD8~+T cells are activated before or at the same time as CD4~+ T cells. These results suggest that CD8~+T cells may play an important role in clearing RSV, downregulation of Th2 cytokine responses and controlling Th2-driven pathology during RSV infection.An ideal RSV vaccine should be capable of inducing humoral immune (antibody) and cellular immune (CTLs), as well as a balanced Th1/Th2 response, which are important to the safety and protective efficacy. We engineered a fusion protein G: 125-225-F/M2:81-95, termed G1F/M2, consisting of an antibody epitope G:125-225(G1) fragment from RSV-A G protein and a CD8~+ T cell epitope (M2:81-95) from RSV-M2 protein. The aim was to develop a safe and effective RSV vaccine.