Congenital and perinatal infection with junin virus in guinea pigs

AbstractJunin virus (JUNV) is a pathogen of biodefense importance due to its potential for aerosol transmission and mortality rates reaching 30%. Currently, there are no JUNV vaccines licensed by the United States Food and Drug Administration (FDA) for at-risk individuals. A vaccine based on recombinant vesicular stomatitis virus (rVSV) has been effectively used to prevent Ebola virus disease in humans. Here, we evaluated the protective efficacy of a rVSV expressing the JUNV glycoprotein (rVSVΔG-JUNVGP) in a guinea pig model of lethal JUNV disease. Two groups of guinea pigs, one prime and one prime-boost, were vaccinated with rVSVΔG-JUNVGP; six control animals remained unvaccinated. Survival for prime and prime-boost vaccinated animals was 100% while the challenge virus was uniformly lethal in all control animals. Animals in both vaccine groups developed robust, high avidity IgG antibody titers post-vaccination as well as detectable neutralizing antibodies while control animals failed to develop detectable antibody responses. This study demonstrates for the first time that rVSV expressing the JUNV GP fully protects guinea pigs from lethal JUNV challenge with a single injection vaccine.

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

Microbiology ◽

10.1099/0022-1317-81-5-1273 ◽

2000 ◽

Vol 81 (5) ◽

pp. 1273-1281 ◽

Cited By ~ 17

Author(s):

Nora López ◽

Luis Scolaro ◽

Carlos Rossi ◽

Rodrigo Jácamo ◽

Nélida Candurra ◽

...

Keyword(s):

Vaccinia Virus ◽

Guinea Pigs ◽

Neutralizing Antibodies ◽

Recombinant Vaccinia Virus ◽

Glycoprotein Precursor ◽

Lethal Challenge ◽

Recombinant Vaccinia ◽

Junin Virus ◽

Virus Challenge ◽

Junín Virus

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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