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

Authors

Bapi Pahar, Tulane National Primate Research Center
Wayne Gray, University of Mississippi
Marissa Fahlberg, Tulane National Primate Research Center
Brooke Grasperge, Tulane National Primate Research Center
Meredith Hunter, Tulane National Primate Research Center
Arpita Das, Tulane National Primate Research Center
Christopher Mabee, Tulane National Primate Research Center
Pyone Pyone Aye, Tulane National Primate Research Center
Faith Schiro, Tulane National Primate Research Center
Krystle Hensley, Tulane National Primate Research Center
Aneeka Ratnayake, Tulane University. School of Public Health and Tropical Medicine
Kelly Goff, Tulane National Primate Research Center
Celia LaBranche, Duke University. School of Medicine
Xiaoying Shen, Duke University. School of Medicine
Georgia D. Tomaras, Duke University. School of Medicine
C. Todd DeMarco, Duke University. School of Medicine
David Montefiori, Duke University. School of Medicine
Patricia Kissinger, Tulane University. School of Public Health and Tropical Medicine
Preston A. Marx, Tulane National Primate Research Center

Document Type

Article

Publication Date

12-1-2022

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.

Relational Format

journal article

Recommended Citation

Pahar, B., Gray, W., Fahlberg, M., Grasperge, B., Hunter, M., Das, A., Mabee, C., Aye, P. P., Schiro, F., Hensley, K., Ratnayake, A., Goff, K., LaBranche, C., Shen, X., Tomaras, G. D., DeMarco, C. T., Montefiori, D., Kissinger, P., Marx, P. A., & Traina-Dorge, V. (2022). 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. Viruses, 14(12), 2819. https://doi.org/10.3390/v14122819

DOI

10.3390/v14122819

Accessibility Status

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