title: An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity.
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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA.
authors: Juan C
authors: JC
authors: Zapata
authors: Bhawna
authors: B
authors: Poonia
authors: Joseph
authors: J
authors: Bryant
authors: Harry
authors: H
authors: Davis
authors: Eugene
authors: E
authors: Ateh
authors: Lanea
authors: L
authors: George
authors: Oswald
authors: O
authors: Crasta
authors: Yan
authors: Y
authors: Zhang
authors: Tom
authors: T
authors: Slezak
authors: Crystal
authors: C
authors: Jaing
authors: C David
authors: CD
authors: Pauza
authors: Marco
authors: M
authors: Goicochea
authors: Dmitry
authors: D
authors: Moshkoff
authors: Igor S
authors: IS
authors: Lukashevich
authors: Maria S
authors: MS
authors: Salvato
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D060085:Coinfection / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D006801:Humans; D007835:Lassa Fever / Q000150:complications / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007836:Lassa virus / Q000276:immunology*; D008253:Macaca mulatta; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
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