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

Zapata, Juan C.; Poonia, Bhawna; Bryant, Joseph; Davis, Harry; Ateh, Eugene; George, Lanea; Crasta, Oswald; Zhang, Yan; Slezak, Tom; Jaing, Crystal; Pauza, C. David; Goicochea, Marco; Moshkoff, Dmitry; Lukashevich, Igor S.; Salvato, Maria S.

doi:10.1186/1743-422x-10-52

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

Journal Article · Tue Feb 12 00:00:00 EST 2013 · Virology Journal

DOI:https://doi.org/10.1186/1743-422x-10-52· OSTI ID:1626615

Zapata, Juan C. ^[1]; Poonia, Bhawna ^[2]; Bryant, Joseph ^[2]; Davis, Harry ^[2]; Ateh, Eugene ^[2]; George, Lanea ^[2]; Crasta, Oswald ^[3]; Zhang, Yan ^[3]; Slezak, Tom ^[4]; Jaing, Crystal ^[4]; Pauza, C. David ^[2]; Goicochea, Marco ^[2]; Moshkoff, Dmitry ^[2]; Lukashevich, Igor S. ^[2]; Salvato, Maria S. ^[2]

Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States). School of Medicine. Inst. of Human Virology; DOE/OSTI
Univ. of Maryland Baltimore County (UMBC), Baltimore, MD (United States). School of Medicine. Inst. of Human Virology
Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States). Virginia Bioinformatics Inst.
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Global Security Directorate

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 cellmediated 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 nonclassical, of arenavirus disease.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOD; USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1626615

Journal Information:: Virology Journal, Journal Name: Virology Journal Journal Issue: 1 Vol. 10; ISSN 1743-422X

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

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

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