Anti‐viral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia‐recombinant virus expressing LCMV‐WE nucleoprotein or glycoprotein

Abstract

The viral antigen specificity of primary cytotoxic T cell responses (CTL) of H‐2^b, H‐2^k, H‐2^q, H‐2^s, H‐2^f and some H‐2‐recombinant mice against lymphocytic choriomeningitis virus (LCMV‐WE isolate) as well as the specificity of some CTL clones and T cell lines was defined on target cells infected with vaccinia‐recombinant virus expressing nucleoprotein (Np) or glycoprotein (Gp). Np was recognized together with H‐2^q (D^q), H‐2^d (DL^d), H‐2^s and H‐2^b (D^b). Gp specificity was restricted to H‐2^f and H‐2^b (K^b and D^b); H‐2^k‐restricted CTL anti‐LCMV responses were neither Gp nor Np specific. The anti‐viral protective immunity induced by vaccinia‐Gp or vaccinia‐Np recombinants was evaluated in mice. In vivo protection was T cell mediated by class I restricted Ly‐2 T cells; it correlated well with the CTL specificity defined in vitro. Some of the CTL‐nonresponder H‐2 allele plus Np or H‐2 plus Gp combinations were, however, protected to variable and low degrees by vaccinia‐recombinant viruses, indicating that anti‐viral protection is a more sensitive readout for CTL activity than the in vitro assay. For example, B10.D2 H‐2^d mice generated measurable CTL responses only to Np; after immunization with a vaccinia‐Np recombinant, LCMV titers were 10⁴ times lower in spleens than in vaccinia‐primed controls. Although vaccinia‐Gp‐immunized BALB/c mice revealed no CTL activity in vitro, they nevertheless had 10² times lower LCMV titers in spleens than controls. Anti‐viral protection, particularly in low‐responder combinations, was usually short‐lived and diminished after 3 weeks. In a high‐responder situation, protection was of a longer duration (> 8 weeks). Vaccination with vaccinia‐Np or Gp recombinants protected mice against lethal T cell‐mediated lymphocytic choriomeningitis induced by LCMV or prevented the local footpad swelling reaction; these in vivo effects were H‐2 dependent and followed the identical roles established for CTL recognition in vitro.