학술논문
Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques
Document Type
article
Author
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; Rama R. Amara
Source
Nature Communications, Vol 14, Iss 1, Pp 1-16 (2023)
Subject
Language
English
ISSN
2041-1723
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.