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

• Type of Material: Article
• Authors: Venkata S. Bollimpelli, Emory University; Pradeep B. J. Reddy, Emory University; Sailaja Gangadhara, Emory University; Tysheena P. Charles, Emory University; Samantha L. Burton, Emory University; Gregory K. Tharp, Emory University; Tiffany M. Styles, Emory University; Celia C. Labranche, Duke University; Justin C. Smith, Louisiana State University; Amit Upadhyay, Emory University; Anusmita Sahoo, Emory University; Traci Legere, Emory University; Ayalnesh Shiferaw, Emory University; Vijayakumar Velu, Emory University; Tianwei Yu, Emory University; Mark Tomai, 3M Corporate Research and Materials Lab; John Vasilakos, 3M Drug Delivery Systems; Sudhir Kasturi, Emory University; George M. Shaw, University of Pennsylvania; David Montefiori, Duke University; Steven Bosinger, Emory University; Pamela A. Kozlowski, Louisiana State University; Bali Pulendran, Emory University; Cynthia Derdeyn, Emory University; Eric Hunter, Emory University; Rama Amara, Emory University
• Language: English
• Date: 2023-08-08
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-023-40430-7
• Title of Journal or Parent Work: NATURE COMMUNICATIONS
• Volume: 14
• Issue: 1
• Start Page: 4789
• End Page: 4789
• Grant/Funding Information: This study was supported by NIH grants UM1 AI124436 (Emory Consortium for Innovative AIDS Research in Nonhuman Primates) to E.H. and R.R.A., the ORIP/NIH base grant P51 OD011132 to ENPRC, NIH grant P30AI050409 to Emory CFAR, and NIH grants AI26683 and OD010976 to Nonhuman Primate Reagent Resource.
• Keywords: MVA; MUCOSAL CHALLENGE; Science & Technology; ANTIBODY-RESPONSES; DNA/MVA VACCINE; IMMUNOGENICITY; INFLAMMASOME; Science & Technology - Other Topics; HIV TYPE-1; CONSTRUCTION; DNA; Multidisciplinary Sciences; DELIVERY
• Research Categories: Health Sciences, Immunology; Biology, Genetics

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.