Publication Date:
2008-11-11
Description:
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 SIV(MAC251) 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614452/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614452/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liu, Jinyan -- O'Brien, Kara L -- Lynch, Diana M -- Simmons, Nathaniel L -- La Porte, Annalena -- Riggs, Ambryice M -- Abbink, Peter -- Coffey, Rory T -- Grandpre, Lauren E -- Seaman, Michael S -- Landucci, Gary -- Forthal, Donald N -- Montefiori, David C -- Carville, Angela -- Mansfield, Keith G -- Havenga, Menzo J -- Pau, Maria G -- Goudsmit, Jaap -- Barouch, Dan H -- AI030034/AI/NIAID NIH HHS/ -- AI066305/AI/NIAID NIH HHS/ -- AI066924/AI/NIAID NIH HHS/ -- AI078526/AI/NIAID NIH HHS/ -- P51 RR000168/RR/NCRR NIH HHS/ -- P51 RR000168-446932/RR/NCRR NIH HHS/ -- P51 RR000168-455647/RR/NCRR NIH HHS/ -- P51 RR000168-466922/RR/NCRR NIH HHS/ -- R01 AI058727/AI/NIAID NIH HHS/ -- R01 AI058727-04/AI/NIAID NIH HHS/ -- R01 AI058727-05/AI/NIAID NIH HHS/ -- R01 AI066924/AI/NIAID NIH HHS/ -- R01 AI066924-02/AI/NIAID NIH HHS/ -- R01 AI066924-03/AI/NIAID NIH HHS/ -- RR000168/RR/NCRR NIH HHS/ -- U19 AI066305/AI/NIAID NIH HHS/ -- U19 AI066305-02/AI/NIAID NIH HHS/ -- U19 AI066305-020001/AI/NIAID NIH HHS/ -- U19 AI066305-03/AI/NIAID NIH HHS/ -- U19 AI066305-030001/AI/NIAID NIH HHS/ -- U19 AI066305-04/AI/NIAID NIH HHS/ -- U19 AI066305-040001/AI/NIAID NIH HHS/ -- U19 AI078526/AI/NIAID NIH HHS/ -- U19 AI078526-01/AI/NIAID NIH HHS/ -- U19 AI078526-017546/AI/NIAID NIH HHS/ -- U19 AI078526-017549/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Jan 1;457(7225):87-91. doi: 10.1038/nature07469. Epub 2008 Nov 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18997770" target="_blank"〉PubMed〈/a〉
Keywords:
Adenoviridae/genetics
;
Animals
;
Antibodies, Viral/immunology
;
CD4-Positive T-Lymphocytes/*immunology
;
HIV Infections/immunology/prevention & control
;
Humans
;
Macaca mulatta/*immunology/*virology
;
Neutralization Tests
;
SAIDS Vaccines/administration & dosage/*immunology
;
Simian Acquired Immunodeficiency Syndrome/*immunology/mortality/prevention &
;
control/virology
;
Simian Immunodeficiency Virus/*immunology
;
Vaccination
;
Viral Load
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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