Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques

Venkata S. Bollimpelli, Pradeep B. J Reddy, Sailaja Gangadhara, Tysheena P. Charles, Samantha L. Burton, Gregory K. Tharp, Tiffany M. Styles, Celia C. Labranche, Justin C. Smith, Amit A. Upadhyay, Anusmita Sahoo, Traci Legere, Ayalnesh Shiferaw, Vijayakumar Velu, Tianwei Yu, Mark Tomai, John Vasilakos, Sudhir P. Kasturi, George M. Shaw, David Montefiori, Steven E. Bosinger, Pamela A. Kozlowski, Bali Pulendran, Cynthia A. Derdeyn, Eric Hunter and Rama R. Amara ()
Additional contact information
Venkata S. Bollimpelli: Emory National Primate Research Center, Emory University
Pradeep B. J Reddy: Emory National Primate Research Center, Emory University
Sailaja Gangadhara: Emory National Primate Research Center, Emory University
Tysheena P. Charles: Emory National Primate Research Center, Emory University
Samantha L. Burton: Emory National Primate Research Center, Emory University
Gregory K. Tharp: Emory National Primate Research Center
Tiffany M. Styles: Emory National Primate Research Center, Emory University
Celia C. Labranche: Duke University School of Medicine
Justin C. Smith: Louisiana State University Health Sciences Center
Amit A. Upadhyay: Emory National Primate Research Center, Emory University
Anusmita Sahoo: Emory National Primate Research Center, Emory University
Traci Legere: Emory National Primate Research Center, Emory University
Ayalnesh Shiferaw: Emory National Primate Research Center, Emory University
Vijayakumar Velu: Emory National Primate Research Center, Emory University
Tianwei Yu: Emory University
Mark Tomai: 3M Corporate Research and Materials Lab
John Vasilakos: 3M Drug Delivery Systems
Sudhir P. Kasturi: Emory National Primate Research Center
George M. Shaw: University of Pennsylvania
David Montefiori: Duke University School of Medicine
Steven E. Bosinger: Emory National Primate Research Center
Pamela A. Kozlowski: Louisiana State University Health Sciences Center
Bali Pulendran: Stanford University School of Medicine, Stanford University
Cynthia A. Derdeyn: Emory National Primate Research Center
Eric Hunter: Emory National Primate Research Center
Rama R. Amara: Emory National Primate Research Center, Emory University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Route of immunization can markedly influence the quality of immune response. Here, we show that intradermal (ID) but not intramuscular (IM) modified vaccinia Ankara (MVA) vaccinations provide protection from acquisition of intravaginal tier2 simian-human immunodeficiency virus (SHIV) challenges in female macaques. Both routes of vaccination induce comparable levels of serum IgG with neutralizing and non-neutralizing activities. The protection in MVA-ID group correlates positively with serum neutralizing and antibody-dependent phagocytic activities, and envelope-specific vaginal IgA; while the limited protection in MVA-IM group correlates only with serum neutralizing activity. MVA-ID immunizations induce greater germinal center Tfh and B cell responses, reduced the ratio of Th1 to Tfh cells in blood and showed lower activation of intermediate monocytes and inflammasome compared to MVA-IM immunizations. This lower innate activation correlates negatively with induction of Tfh responses. These data demonstrate that the MVA-ID vaccinations protect against intravaginal SHIV challenges by modulating the innate and T helper responses.

Date: 2023
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DOI: 10.1038/s41467-023-40430-7

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