title: Vesicular stomatitis virus-simian retrovirus type 2 vaccine protects macaques from detectable infection and B-cell destruction.
abstract: Natural infection with simian retrovirus (SRV) has long been recognized in rhesus macaques (RMs) and may result in an AIDS-like disease. Importantly, SRV infections persist as a problem in recently imported macaques. Therefore, there is a clear need to control SRV spread in macaque colonies. We developed a recombinant vesicular stomatitis virus (VSV)-SRV vaccine consisting of replication-competent hybrid VSVs that express SRV gag and env in separate vectors. The goal of this study was to assess the immunogenicity and protective efficacy of the VSV-SRV serotype 2 vaccine prime-boost approach in RMs. The VSV-SRV vector (expressing either SRV gag or env) vaccines were intranasally administered in 4 RMs, followed by a boost 1 month after the first vaccination. Four RMs served as controls and received the VSV vector alone. Two months after the boost, all animals were intravenously challenged with SRV-2 and monitored for 90 days. After the SRV-2 challenge, all four controls became infected, and viral loads (VLs) ranged from 10(6) to 10(8) SRV RNA copies/ml of plasma. Two animals in the control group developed simian AIDS within 7 to 8 weeks postinfection and were euthanized. Anemia and weight loss were observed in the remaining controls. During acute infection, severe B-cell depletion and no significant changes in T-cell population were observed in the control group. Control RMs with greater preservation of B cells and lower VLs survived longer. SRV-2 was undetectable in vaccinated animals, which remained healthy, with no clinical or biological signs of infection and preservation of B cells. Our study showed that the VSV-SRV vaccine is a strong approach for preventing clinically relevant type D retrovirus infection and disease in RMs, with protection of 4/4 RMs from SRV infection and prevention of B-cell destruction. B-cell protection was the strongest correlate of the long-term survival of all vaccinated and control RMs.
authors.affiliation: Division of Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Gautam
authors.forename: Arun
authors.initials: A
authors.lastname: Iyer
authors.forename: Meredith
authors.initials: M
authors.lastname: Hunter
authors.forename: Arpita
authors.initials: A
authors.lastname: Das
authors.forename: Tessa
authors.initials: T
authors.lastname: Williams
authors.forename: Jason
authors.initials: J
authors.lastname: Dufour
authors.forename: Cristian
authors.initials: C
authors.lastname: Apetrei
authors.forename: K Gus
authors.initials: KG
authors.lastname: Kousoulas
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors / Q000008:administration & dosage*; D007114:Immunization; D007117:Immunization, Secondary; D008253:Macaca mulatta; D016093:Mason-Pfizer monkey virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D018116:Vesiculovirus / Q000235:genetics*
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D018449:SAIDS Vaccines