Homologous and heterologous glycoproteins induce protection against Junin virus challenge in guinea pigs

Tacaribe virus (TACV) is an arenavirus that is genetically and: antigenical ly closely related to Junin virus (JUNV), the aetiological agent of Argenti ne haemorrhagic fever (AHF). It is well established that TACV protects expe rimental animals fully against an otherwise lethal challenge with JUNV. To gain information on the nature of the antigens involved in cross-protection , recombinant vaccinia viruses were constructed that express the glycoprote in precursor (VV-GTac) or the nucleocapsid protein (VV-N) of TACV. TACV pro teins expressed by vaccinia virus were indistinguishable from authentic vir us proteins by gel electrophoresis. Guinea pigs inoculated with VV-GTac or VV-N elicited antibodies that immunoprecipitated authentic TACV proteins. A ntibodies generated by VV-GTac neutralized TACV infectivity, Levels of anti bodies after priming and boosting with recombinant vaccinia virus were comp arable to those elicited in TACV infection. To evaluate the ability of reco mbinant vaccinia virus to protect against experimental AHF, guinea pigs wer e challenged with lethal doses of JUNV. Fifty per cent of the animals immun ized with VV-GTac survived, whereas all animals inoculated with VV-N or vac cinia virus died. Having established that the heterologous glycoprotein pro tects against JUNV challenge, a recombinant vaccinia virus was constructed that expresses JUNV glycoprotein precursor (VV-GJun). The size and reactivi ty to monoclonal antibodies of the vaccinia virus-expressed and authentic J UNV glycoproteins were indistinguishable. Seventy-two per cent of the anima ls inoculated with two doses of VV-GJun survived lethal JUNV challenge. Pro tection with either VV-GJun or VV-GTac occurred in the presence of low or u ndetectable levels of neutralizing antibodies to JUNV.