b-30-muramyl-dipeptide and Orthomyxoviridae-Infections

We examined the characterization of the antiviral T lymphocytes elicited by immunization with a novel liposome vaccine (MDP-virosome) constructed with synthetic muramyldipeptide; [6-0-(2-tetradecylhexadecanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutamine] , cholesterol, influenza virus haemagglutinin and neuraminidase. The haemagglutinin glycoprotein first appeared to induce a significant subtype-specific cytotoxic activity through its arrangement on the inner and outer surfaces of the MDP-virosome. Splenocytes of BALB/c mice immunized with the virosome vaccine containing H3 haemagglutinin and N2 neuraminidase from human Hong Kong virus markedly lysed H3N2 virus-infected target cells, but not those infected with virus possessing a different subtype such as H1N1 surface antigens. Exposure of these splenic lymphocytes to virus antigen in vitro further enhanced their cytotoxic activity. The cytotoxic lymphocytes 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 spleen cells suggested that the MDP-virosome vaccination is able to protect against influenza virus infection through enhanced cellular immune responses.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Adjuvants, Immunologic; Animals; Cytotoxicity, Immunologic; Hemagglutinins, Viral; Histocompatibility Antigens Class II; Immunity, Cellular; Influenza Vaccines; Liposomes; Lung; Lymphocyte Subsets; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Orthomyxoviridae Infections; T-Lymphocytes, Cytotoxic

A synthetic muramyldipeptide (MDP) and two analogues, B30-MDP and MDP-Lys(L18), augmented serum interferon (IFN) production in mice by the inducers lipopolysaccharide (LPS) and polyinosinic acid:polycytidylic acid (poly I:C), and also augmented immune IFN production induced by purified protein derivative (PPD) in mycobacteria-sensitized mice. These compounds were most effective when administered to mice one day before the interferon inducer. By contrast, IFN production in mice by either oral tilorone or virus infection was not enhanced with these compounds. Since LPS and poly I:C are well known as early-type IFN inducers, and tilorone and virus infection are late-type inducers, we presume that MDP and its analogues are able to augment only early-type IFN production. This enhancing effect may be mediated by macrophage activation. In vivo antiviral activity of MDP and its analogues was further tested in mice infected with vaccinia virus (VV) using early-type inducers. When mice previously treated with MDP or its analogues were stimulated for IFN production with a low dose of LPS, protective activity against VV infection was markedly enhanced.

Topics: Acetylmuramyl-Alanyl-Isoglutamine; Animals; Cell Line; Female; Interferon Inducers; Interferon-gamma; Interferons; Lipopolysaccharides; Macrophage Activation; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Poly I-C; Tilorone; Vaccinia