Title
Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys
Author
Liu, J.
O'Brien, K.L.
Lynch, D.M.
Simmons, N.L.
La Porte, A.
Riggs, A.M.
Abbink, P.
Coffey, R.T.
Grandpre, L.E.
Seaman, M.S.
Landucci, G.
Forthal, D.N.
Montefiori, D.C.
Carville, A.
Mansfield, K.G.
Havenga, M.J.
Pau, M.G.
Goudsmit, J.
Barouch, D.H.
TNO Kwaliteit van Leven
Publication year
2009
Abstract
A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys (Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 (ref. 3). Here we show that an improved T-cell-based vaccine regimen using two serologically distinct adenovirus vectors afforded substantially improved protective efficacy in this challenge model. In particular, a heterologous rAd26 prime/rAd5 boost vaccine regimen expressing SIV Gag elicited cellular immune responses with augmented magnitude, breadth and polyfunctionality as compared with the homologous rAd5 regimen. After SIVMAC251 challenge, monkeys vaccinated with the rAd26/rAd5 regimen showed a 1.4 log reduction of peak and a 2.4 log reduction of setpoint viral loads as well as decreased AIDS-related mortality as compared with control animals. These data demonstrate that durable partial immune control of a pathogenic SIV challenge for more than 500 days can be achieved by a T-cell-based vaccine in Mamu-A*01-negative rhesus monkeys in the absence of a homologous Env antigen. These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1. ©2009 Macmillan Publishers Limited. All rights reserved.
Subject
Health
Biomedical Research
adenovirus vector
antigen
vaccine
allele
cytology
gene expression
human immunodeficiency virus
immune response
primate
recombination
vaccine
acquired immune deficiency syndrome
animal experiment
animal model
article
cellular immunity
controlled study
immune response
immunogenicity
mortality
nonhuman
priority journal
rhesus monkey
serology
Simian immunodeficiency virus
T lymphocyte
therapy effect
virus load
Adenoviridae
Animals
Antibodies, Viral
CD4-Positive T-Lymphocytes
HIV Infections
Humans
Macaca mulatta
Neutralization Tests
SAIDS Vaccines
Simian Acquired Immunodeficiency Syndrome
Simian immunodeficiency virus
Vaccination
Viral Load
Adenoviridae
Animalia
Human immunodeficiency virus 1
Macaca mulatta
Simian immunodeficiency virus
To reference this document use:
http://resolver.tudelft.nl/uuid:887d420c-28df-4d78-b355-a7c8a1029b59
DOI
https://doi.org/10.1038/nature07469
TNO identifier
285081
Source
Nature, 457 (7225), 87-91
Document type
article