CHARACTERISTICS OF CYTOTOXIC T-LYMPHOCYTES DIRECTED TO INFLUENZA-VIRUS HEMAGGLUTININ ELICITED BY IMMUNIZATION WITH MURAMYLDIPEPTIDE-INFLUENZA LIPOSOME VACCINE

We examined the characterization of the antiviral T lymphocytes elicit ed by immunization with a novel liposome vaccine (MDP-virosome) constr ucted with synthetic muramyldipeptide;[6-O-(2-tetradecyl-hexadecanoyl) -N-acetylmuramyl-L-alanyl-D-isoglutamine], cholesterol, influenza vir us haemagglutinin and neuraminidase. The haemagglutinin glycoprotein f irst appeared to induce a significant subtype-specific cytotoxic activ ity through its arrangement on the inner and outer surfaces of the MDP -virosome. Splenocytes of BALB/c mice immunized with the virosome vacc ine containing H3 haemagglutinin and N2 neuraminidase from human Hong Kong virus markedly lysed H3N2 virus-infected target cells, but not th ose infected with virus possessing a different subtype such as H1N1 su rface antigens. Exposure of these splenic lymphocytes to virus antigen in vitro further enhanced their cytotoxic activity. The cytotoxic lym phocytes generated by the MDP-virosome vaccine expressed Thy 1 and CD4 antigens on their cell surface, and these activities were restricted by class II histocompatibility gene products. The marked reduction of pulmonary virus titres in infected mice caused by transferred immune s pleen cells suggested that the MDP-virosome vaccination is able to pro tect against influenza virus infection through enhanced cellular immun e responses.