Open AccessEngagement of monocytes, NK cells, and CD4+ Th1 cells by ALVAC-SIV vaccination results in a decreased risk of SIVmac251 vaginal acquisition
Author(s) -
Giacomo Gorini,
Slim Fourati,
Monica Vaccari,
Mohammad Arif Rahman,
Shari N. Gordon,
Dallas R. Brown,
G. Lynn Law,
Jean Chang,
Richard Green,
Fredrik Barrenäs,
Namal P. M. Liyanage,
Melvin N. Doster,
Luca Schifanella,
Massimiliano Bissa,
Isabela Silva de Castro,
Robyn Washington-Parks,
Veronica Galli,
Deborah H. Fuller,
Sampa Santra,
Michael B. Agy,
Ranajit Pal,
Robert E. Palermo,
Georgia D. Tomaras,
Xiaoying Shen,
Celia C. LaBranche,
David C. Montefiori,
David Venzon,
Hung V. Trinh,
Mangala Rao,
Michael Gale,
Rafick Pierre Sékaly,
Genoveffa Franchini
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008377
Subject(s) - immunology , cd14 , immune system , regimen , virology , vaccination , biology , cd38 , medicine , cd34 , genetics , stem cell
The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease the risk of HIV acquisition in humans, with equal effectiveness in both males and females. Similarly, an equivalent SIV-based ALVAC vaccine regimen decreased the risk of virus acquisition in Indian rhesus macaques of both sexes following intrarectal exposure to low doses of SIV mac251 . Here, we demonstrate that the ALVAC-SIV/gp120/alum vaccine is also efficacious in female Chinese rhesus macaques following intravaginal exposure to low doses of SIV mac251 and we confirm that CD14 + classical monocytes are a strong correlate of decreased risk of virus acquisition. Furthermore, we demonstrate that the frequency of CD14 + cells and/or their gene expression correlates with blood Type 1 CD4 + T helper cells, α 4 β 7 + plasmablasts, and vaginal cytocidal NKG2A + cells. To better understand the correlate of protection, we contrasted the ALVAC-SIV vaccine with a NYVAC-based SIV/gp120 regimen that used the identical immunogen. We found that NYVAC-SIV induced higher immune activation via CD4 + Ki67 + CD38 + and CD4 + Ki67 + α 4 β 7 + T cells, higher SIV envelope-specific IFN-γ producing cells, equivalent ADCC, and did not decrease the risk of SIV mac251 acquisition. Using the systems biology approach, we demonstrate that specific expression profiles of plasmablasts, NKG2A + cells, and monocytes elicited by the ALVAC-based regimen correlated with decreased risk of virus acquisition.