Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques

Abstract

HIV vaccine mediated efficacy, using an expanded live attenuated recombinant varicella virus-vectored SIV rSVV-SIVgag/env vaccine prime with adjuvanted SIV-Env and SIV-Gag protein boosts, was evaluated in a female rhesus macaques (RM) model against repeated intravaginal SIV challenges. Vaccination induced anti-SIV IgG responses and neutralizing antibodies were found in all vaccinated RMs. Three of the eight vaccinated RM remained uninfected (vaccinated and protected, VP) after 13 repeated challenges with the pathogenic SIVmac251-CX-1. The remaining five vaccinated and infected (VI) macaques had significantly reduced plasma viral loads compared with the infected controls (IC). A significant increase in systemic central memory CD4+ T cells and mucosal CD8+ effector memory T-cell responses was detected in vaccinated RMs compared to controls. Variability in lymph node SIV-Gag and Env specific CD4+ and CD8+ T cell cytokine responses were detected in the VI RMs while all three VP RMs had more durable cytokine responses following vaccination and prior to challenge. VI RMs demonstrated predominately SIV-specific monofunctional cytokine responses while the VP RMs generated polyfunctional cytokine responses. This study demonstrates that varicella virus-vectored SIV vaccination with protein boosts induces a 37.5% efficacy rate against pathogenic SIV challenge by generating mucosal memory, virus specific neutralizing antibodies, binding antibodies, and polyfunctional T-cell responses.

Toll-like Receptor 2 Mediated Immune Regulation in Simian Immunodeficiency Virus-Infected Rhesus Macaques

“…PBMCs were isolated from heparinized whole blood by Ficoll density gradient centrifugation [ 35 , 36 ]. Briefly, the plasma from the whole blood was separated by centrifugation at 2500 rpm for 10 min.…”

“…Peripheral LNs were processed, as discussed previously [ 35 , 36 ]. In brief, the tissue was collected in complete media, taken in the lab, cut into small pieces, and transferred onto a 70 µm strainer placed in a Petri dish.…”

“…Freshly isolated PBMCs, jejunum LPL, and LN cells were stained for flow cytometry following the protocol reported earlier [ 8 , 35 , 37 ]. In brief, 1–1.5 × 10 6 mL cells were stimulated with Staphylococcal enterotoxin (SEB, Toxin Technologies, Sarasota, FL, USA) at 5 µg/mL and kept overnight in a 5% CO 2 incubator at 37 °C.…”