Open Access Research

An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity

Juan C Zapata1, Bhawna Poonia1, Joseph Bryant1, Harry Davis1, Eugene Ateh1, Lanea George1, Oswald Crasta2, Yan Zhang2, Tom Slezak3, Crystal Jaing3, C David Pauza1, Marco Goicochea1, Dmitry Moshkoff1, Igor S Lukashevich14 and Maria S Salvato1*

Author Affiliations

1 Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA

2 Virginia Bioinformatics Institute at Virginia Tech, Blacksburg, VA 24061, USA

3 Global Security Directorate, Lawrence Livermore National Laboratory, 7000 East Ave, Livermore, CA 94550, USA

4 New address for ISL: NIH National Regional Biocontainment Laboratory, 950 N Hurstbourne Pkwy, Louisville, KY 40222, USA

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Virology Journal 2013, 10:52  doi:10.1186/1743-422X-10-52

Published: 12 February 2013

Abstract

Background

Lassa hemorrhagic fever (LHF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs pathognomonic for arenavirus disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LHF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of HIV infection.

Results

SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for specific humoral and cellular immune responses, as well as for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, respiratory distress, malaise, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs, derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections, included increased expression of interferon-stimulated genes (ISG) and decreased expression of COX2, IL-1β, coagulation intermediates and nuclear receptors needed for stress signaling. All vaccinated monkeys showed ML29-specific antibody responses and ML29-specific cell-mediated immunity.

Conclusion

SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and none developed chronic arenavirus infection. Importantly, none of the macaques developed signs, classical or non-classical, of arenavirus disease.

Keywords:
Lassa fever virus; Vaccine; Macaque; SIV-infected; Genomic profiling; Disease markers