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  • 1
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    Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys (2008)
    Nature Publishing Group (NPG)
    Details
    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
    Published by Nature Publishing Group (NPG)
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  • 2
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    Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-01-06
    Description: Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3271177/" 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/PMC3271177/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barouch, Dan H -- Liu, Jinyan -- Li, Hualin -- Maxfield, Lori F -- Abbink, Peter -- Lynch, Diana M -- Iampietro, M Justin -- SanMiguel, Adam -- Seaman, Michael S -- Ferrari, Guido -- Forthal, Donald N -- Ourmanov, Ilnour -- Hirsch, Vanessa M -- Carville, Angela -- Mansfield, Keith G -- Stablein, Donald -- Pau, Maria G -- Schuitemaker, Hanneke -- Sadoff, Jerald C -- Billings, Erik A -- Rao, Mangala -- Robb, Merlin L -- Kim, Jerome H -- Marovich, Mary A -- Goudsmit, Jaap -- Michael, Nelson L -- AI002642/AI/NIAID NIH HHS/ -- AI060354/AI/NIAID NIH HHS/ -- AI066924/AI/NIAID NIH HHS/ -- AI078526/AI/NIAID NIH HHS/ -- AI084794/AI/NIAID NIH HHS/ -- AI095985/AI/NIAID NIH HHS/ -- P01 AI095985/AI/NIAID NIH HHS/ -- P01 AI095985-01/AI/NIAID NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- R01 AI066924/AI/NIAID NIH HHS/ -- R01 AI066924-05/AI/NIAID NIH HHS/ -- R01 AI084794/AI/NIAID NIH HHS/ -- R01 AI084794-03/AI/NIAID NIH HHS/ -- RR000168/RR/NCRR NIH HHS/ -- U19 AI066305/AI/NIAID NIH HHS/ -- U19 AI066305-05/AI/NIAID NIH HHS/ -- U19 AI078526/AI/NIAID NIH HHS/ -- U19 AI078526-04/AI/NIAID NIH HHS/ -- U19 AI095985/AI/NIAID NIH HHS/ -- England -- Nature. 2012 Jan 4;482(7383):89-93. doi: 10.1038/nature10766.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. dbarouch@bidmc.harvard.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22217938" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/immunology ; Adenoviridae/genetics/immunology ; Animals ; Antibodies, Neutralizing/*immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; HIV-1/immunology ; Macaca mulatta/*immunology ; Male ; Neutralization Tests ; SAIDS Vaccines/*immunology ; Simian Immunodeficiency Virus/*immunology ; Viral Vaccines/immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    PG9 glycosylation and sulfation in plants [Applied Biological Sciences] (2015)
    National Academy of Sciences
    Details
    Publication Date: 2015-10-14
    Description: Broadly neutralizing anti–HIV-1 monoclonal antibodies, such as PG9, and its derivative RSH hold great promise in AIDS therapy and prevention. An important feature related to the exceptional efficacy of PG9 and RSH is the presence of sulfated tyrosine residues in their antigen-binding regions. To maximize antibody functionalities, we have now...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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