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Journal of General Virology (2000), 81, 1273-1281.
© 2000 Society for General Microbiology


Animal: RNA Viruses

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

Nora López1, Luis Scolaro2, Carlos Rossi,1,3, Rodrigo Jácamo1, Nélida Candurra2, Carlos Pujol2, Elsa B. Damonte2 and María T. Franze-Fernández1

Centro de Virología Animal, Serrano 669, 1414 Buenos Aires, Argentina1
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428 Buenos Aires, Argentina2
Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina3

Author for correspondence: María Franze-Fernández. Fax +54 11 4825 1863. e-mail mtff{at}cevan.sld.ar

Tacaribe virus (TACV) is an arenavirus that is genetically and antigenically closely related to Junin virus (JUNV), the aetiological agent of Argentine haemorrhagic fever (AHF). It is well established that TACV protects experimental 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 glycoprotein precursor (VV–GTac) or the nucleocapsid protein (VV–N) of TACV. TACV proteins expressed by vaccinia virus were indistinguishable from authentic virus proteins by gel electrophoresis. Guinea pigs inoculated with VV–GTac or VV–N elicited antibodies that immunoprecipitated authentic TACV proteins. Antibodies generated by VV–GTac neutralized TACV infectivity. Levels of antibodies after priming and boosting with recombinant vaccinia virus were comparable to those elicited in TACV infection. To evaluate the ability of recombinant vaccinia virus to protect against experimental AHF, guinea pigs were challenged with lethal doses of JUNV. Fifty per cent of the animals immunized with VV–GTac survived, whereas all animals inoculated with VV–N or vaccinia virus died. Having established that the heterologous glycoprotein protects against JUNV challenge, a recombinant vaccinia virus was constructed that expresses JUNV glycoprotein precursor (VV–GJun). The size and reactivity to monoclonal antibodies of the vaccinia virus-expressed and authentic JUNV glycoproteins were indistinguishable. Seventy-two per cent of the animals inoculated with two doses of VV–GJun survived lethal JUNV challenge. Protection with either VV–GJun or VV–GTac occurred in the presence of low or undetectable levels of neutralizing antibodies to JUNV.




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