Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors

Steven Tuyishime; Larissa H. Haut; Raj K. Kurupati; James M. Billingsley; Diane Carnathan; Sailaja Gangahara; Tiffany M. Styles; Zhi Quan Xiang; Yan Li; Malte Zopfs; Qin Liu; Xiang Yang Zhou; Mark G. Lewis; Rama R. Amara; Steven Bosinger; Guido Silvestri; Hildegund C.J. Ertl

doi:10.1016/j.ebiom.2018.02.025

Correlates of Protection Against SIV_mac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors

Steven Tuyishime
, Larissa H. Haut
, Raj K. Kurupati
, James M. Billingsley
, Diane Carnathan
, Sailaja Gangahara
, Tiffany M. Styles
, Zhi Quan Xiang
, Yan Li
, Malte Zopfs
, Qin Liu
, Xiang Yang Zhou
, Mark G. Lewis
, Rama R. Amara
, Steven Bosinger
, Guido Silvestri
, Hildegund C.J. Ertl^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

We report on prime-boost vaccine regimens with two simian adenovirus (Ad) vectors (SAdV) or two human serotype Ad vectors (HAdV) expressing Gag and gp160 of simian immunodeficiency virus (SIV)_mac239 tested in HAdV-seropositive rhesus macaques (RMs) repeatedly challenged rectally with low doses of SIV_mac251. Both vaccine regimens reduced set point and peak viral loads (PVL) and accelerated viral clearance. In SAdV-vaccinated controller genotype RMs resistance against infection correlated with levels of envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8⁺T cells controlled viral loads (VL) upon infection. Circulating CD4⁺ and CD8⁺ T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (T_FH) cell responses and highly activated CD8⁺ T cells may play a role in protection.

Original language	English
Pages (from-to)	25-35
Number of pages	11
Journal	eBioMedicine
Volume	31
DOIs	https://doi.org/10.1016/j.ebiom.2018.02.025
State	Published - May 2018
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Adenovirus vector
Gene expression profiles
HIV-1 vaccine
Mucosal challenge
Protection

Access to Document

10.1016/j.ebiom.2018.02.025

Cite this

Tuyishime, S., Haut, L. H., Kurupati, R. K., Billingsley, J. M., Carnathan, D., Gangahara, S., Styles, T. M., Xiang, Z. Q., Li, Y., Zopfs, M., Liu, Q., Zhou, X. Y., Lewis, M. G., Amara, R. R., Bosinger, S., Silvestri, G., & Ertl, H. C. J. (2018). Correlates of Protection Against SIV_mac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors. eBioMedicine, 31, 25-35. https://doi.org/10.1016/j.ebiom.2018.02.025

@article{e9b1868aeb5442d59ab6d4157f866a58,

title = "Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors",

abstract = "We report on prime-boost vaccine regimens with two simian adenovirus (Ad) vectors (SAdV) or two human serotype Ad vectors (HAdV) expressing Gag and gp160 of simian immunodeficiency virus (SIV)mac239 tested in HAdV-seropositive rhesus macaques (RMs) repeatedly challenged rectally with low doses of SIVmac251. Both vaccine regimens reduced set point and peak viral loads (PVL) and accelerated viral clearance. In SAdV-vaccinated controller genotype RMs resistance against infection correlated with levels of envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8+T cells controlled viral loads (VL) upon infection. Circulating CD4+ and CD8+ T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (TFH) cell responses and highly activated CD8+ T cells may play a role in protection.",

keywords = "Adenovirus vector, Gene expression profiles, HIV-1 vaccine, Mucosal challenge, Protection",

author = "Steven Tuyishime and Haut, \{Larissa H.\} and Kurupati, \{Raj K.\} and Billingsley, \{James M.\} and Diane Carnathan and Sailaja Gangahara and Styles, \{Tiffany M.\} and Xiang, \{Zhi Quan\} and Yan Li and Malte Zopfs and Qin Liu and Zhou, \{Xiang Yang\} and Lewis, \{Mark G.\} and Amara, \{Rama R.\} and Steven Bosinger and Guido Silvestri and Ertl, \{Hildegund C.J.\}",

note = "Publisher Copyright: {\textcopyright} 2018",

year = "2018",

month = may,

doi = "10.1016/j.ebiom.2018.02.025",

language = "英语",

volume = "31",

pages = "25--35",

journal = "eBioMedicine",

issn = "2352-3964",

publisher = "Elsevier B.V.",

}

Tuyishime, S, Haut, LH, Kurupati, RK, Billingsley, JM, Carnathan, D, Gangahara, S, Styles, TM, Xiang, ZQ, Li, Y, Zopfs, M, Liu, Q, Zhou, XY, Lewis, MG, Amara, RR, Bosinger, S, Silvestri, G & Ertl, HCJ 2018, 'Correlates of Protection Against SIV_mac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors', eBioMedicine, vol. 31, pp. 25-35. https://doi.org/10.1016/j.ebiom.2018.02.025

TY - JOUR

T1 - Correlates of Protection Against SIVmac251 Infection in Rhesus Macaques Immunized With Chimpanzee-Derived Adenovirus Vectors

AU - Tuyishime, Steven

AU - Haut, Larissa H.

AU - Kurupati, Raj K.

AU - Billingsley, James M.

AU - Carnathan, Diane

AU - Gangahara, Sailaja

AU - Styles, Tiffany M.

AU - Xiang, Zhi Quan

AU - Li, Yan

AU - Zopfs, Malte

AU - Liu, Qin

AU - Zhou, Xiang Yang

AU - Lewis, Mark G.

AU - Amara, Rama R.

AU - Bosinger, Steven

AU - Silvestri, Guido

AU - Ertl, Hildegund C.J.

PY - 2018/5

Y1 - 2018/5

N2 - We report on prime-boost vaccine regimens with two simian adenovirus (Ad) vectors (SAdV) or two human serotype Ad vectors (HAdV) expressing Gag and gp160 of simian immunodeficiency virus (SIV)mac239 tested in HAdV-seropositive rhesus macaques (RMs) repeatedly challenged rectally with low doses of SIVmac251. Both vaccine regimens reduced set point and peak viral loads (PVL) and accelerated viral clearance. In SAdV-vaccinated controller genotype RMs resistance against infection correlated with levels of envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8+T cells controlled viral loads (VL) upon infection. Circulating CD4+ and CD8+ T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (TFH) cell responses and highly activated CD8+ T cells may play a role in protection.

AB - We report on prime-boost vaccine regimens with two simian adenovirus (Ad) vectors (SAdV) or two human serotype Ad vectors (HAdV) expressing Gag and gp160 of simian immunodeficiency virus (SIV)mac239 tested in HAdV-seropositive rhesus macaques (RMs) repeatedly challenged rectally with low doses of SIVmac251. Both vaccine regimens reduced set point and peak viral loads (PVL) and accelerated viral clearance. In SAdV-vaccinated controller genotype RMs resistance against infection correlated with levels of envelope (Env)-specific antibody (Ab) titers. In both vaccine groups CD8+T cells controlled viral loads (VL) upon infection. Circulating CD4+ and CD8+ T cells showed significant changes in their transcriptome over time following vaccination, which differed between the vaccine groups. T cells from SIV-resistant RMs had unique transcriptional profiles indicating that both follicular T helper (TFH) cell responses and highly activated CD8+ T cells may play a role in protection.

KW - Adenovirus vector

KW - Gene expression profiles

KW - HIV-1 vaccine

KW - Mucosal challenge

KW - Protection

UR - https://www.scopus.com/pages/publications/85045953696

U2 - 10.1016/j.ebiom.2018.02.025

DO - 10.1016/j.ebiom.2018.02.025

M3 - 文章

C2 - 29685793

AN - SCOPUS:85045953696

SN - 2352-3964

VL - 31

SP - 25

EP - 35

JO - eBioMedicine

JF - eBioMedicine

ER -