Print Email Facebook Twitter Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys 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 HealthBiomedical Researchadenovirus vectorantigenvaccineallelecytologygene expressionhuman immunodeficiency virusimmune responseprimaterecombinationvaccineacquired immune deficiency syndromeanimal experimentanimal modelarticlecellular immunitycontrolled studyimmune responseimmunogenicitymortalitynonhumanpriority journalrhesus monkeyserologySimian immunodeficiency virusT lymphocytetherapy effectvirus loadAdenoviridaeAnimalsAntibodies, ViralCD4-Positive T-LymphocytesHIV InfectionsHumansMacaca mulattaNeutralization TestsSAIDS VaccinesSimian Acquired Immunodeficiency SyndromeSimian immunodeficiency virusVaccinationViral LoadAdenoviridaeAnimaliaHuman immunodeficiency virus 1Macaca mulattaSimian 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 Files To receive the publication files, please send an e-mail request to TNO Library.