NUCLEIC-ACID VACCINATION PRIMES HEPATITIS-B VIRUS SURFACE ANTIGEN-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN NONRESPONDER MICE

The efficiency of different vaccination techniques to prime in vivo ma jor histocompatibility complex class I-restricted murine cytotoxic T-l ymphocyte (CTL) precursors to hepatitis B virus small surface antigen (HBsAg) was investigated. Mice were immunized either by injection of a low dose of recombinant HBsAg protein preparations (native HBsAg part icles or denatured HBsAg monomers) without adjuvants, by infection wit h recombinant vaccinia virus carrying an HBsAg-encoding gene, or by in tramuscular transfer of plasmid DNA encoding HBsAg under appropriate p romoter control, In H-2(d) mice, an L(d)-restricted, S-28-39-specific CTL response was efficiently primed by all alternative vaccination tec hniques tested, but the most potent priming of class I-restricted CTL to HBsAg in vivo was observed with DNA immunization, Priming of anti-H BsAg CTL in H-2(b) mice was not detectable after infection with a reco mbinant vaccinia virus or after injection with exogenous recombinant H BsAg preparations, After DNA immunization, however, both K-b- and D-b- restricted CTL reactivity to HBsAg emerged in H-2(b) mice, Hence, nucl eic acid immunization revealed class I-restricted CTL responsiveness t o HBsAg in a mouse strain previously considered to be a nonresponder a t the CTL level. These results demonstrate that the simple technique o f nucleic acid immunization not only is extremely efficient but also r eveals an extended spectrum of potentially immunogenic epitopes of pro tein antigens.