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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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    Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys (2015)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2015-07-04
    Description: Preclinical studies of viral vector-based HIV-1 vaccine candidates have previously shown partial protection against neutralization-resistant virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy of adenovirus serotype 26 (Ad26) vector priming followed by purified envelope (Env) glycoprotein boosting. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env, Gag, and Pol and boosted with AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete protection in 50% of vaccinated animals against a series of repeated, heterologous, intrarectal SIVmac251 challenges that infected all controls. Protective efficacy correlated with the functionality of Env-specific antibody responses. Comparable protection was also observed with a similar Ad/Env vaccine against repeated, heterologous, intrarectal SHIV-SF162P3 challenges. These data demonstrate robust protection by Ad/Env vaccines against acquisition of neutralization-resistant virus challenges in rhesus monkeys.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653134/" 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/PMC4653134/" 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 -- Alter, Galit -- Broge, Thomas -- Linde, Caitlyn -- Ackerman, Margaret E -- Brown, Eric P -- Borducchi, Erica N -- Smith, Kaitlin M -- Nkolola, Joseph P -- Liu, Jinyan -- Shields, Jennifer -- Parenteau, Lily -- Whitney, James B -- Abbink, Peter -- Ng'ang'a, David M -- Seaman, Michael S -- Lavine, Christy L -- Perry, James R -- Li, Wenjun -- Colantonio, Arnaud D -- Lewis, Mark G -- Chen, Bing -- Wenschuh, Holger -- Reimer, Ulf -- Piatak, Michael -- Lifson, Jeffrey D -- Handley, Scott A -- Virgin, Herbert W -- Koutsoukos, Marguerite -- Lorin, Clarisse -- Voss, Gerald -- Weijtens, Mo -- Pau, Maria G -- Schuitemaker, Hanneke -- AI060354/AI/NIAID NIH HHS/ -- AI078526/AI/NIAID NIH HHS/ -- AI080289/AI/NIAID NIH HHS/ -- AI084794/AI/NIAID NIH HHS/ -- AI095985/AI/NIAID NIH HHS/ -- AI096040/AI/NIAID NIH HHS/ -- AI102660/AI/NIAID NIH HHS/ -- AI102691/AI/NIAID NIH HHS/ -- OD011170/OD/NIH HHS/ -- P30 AI060354/AI/NIAID NIH HHS/ -- R01 AI080289/AI/NIAID NIH HHS/ -- R01 AI084794/AI/NIAID NIH HHS/ -- R01 AI102660/AI/NIAID NIH HHS/ -- R01 AI102691/AI/NIAID NIH HHS/ -- R01 OD011170/OD/NIH HHS/ -- R37 AI080289/AI/NIAID NIH HHS/ -- U19 AI078526/AI/NIAID NIH HHS/ -- U19 AI095985/AI/NIAID NIH HHS/ -- U19 AI096040/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 17;349(6245):320-4. doi: 10.1126/science.aab3886. Epub 2015 Jul 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA. dbarouch@bidmc.harvard.edu. ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA. ; Thayer School of Engineering at Dartmouth, Hanover, NH 03755, USA. ; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. ; University of Massachusetts Medical School, Worcester, MA 01605, USA. ; New England Primate Research Center, Southborough, MA 01772, USA. ; Bioqual, Rockville, MD 20852, USA. ; Children's Hospital, Boston, MA 02115, USA. ; JPT Peptide Technologies GmbH, 12489 Berlin, Germany. ; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA. ; Washington University School of Medicine, St. Louis, MO 63110, USA. ; GSK Vaccines, 1330 Rixensart, Belgium. ; Janssen Infectious Diseases and Vaccines (formerly Crucell), 2301 Leiden, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138104" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; Adenovirus Vaccines/*immunology ; Adoptive Transfer ; Animals ; Antibodies, Neutralizing/immunology ; Female ; Gene Products, env/*immunology ; Gene Products, gag/immunology ; Gene Products, pol/immunology ; Genetic Vectors/immunology ; HIV-1/*immunology ; Histocompatibility Antigens Class I/genetics/immunology ; Immunization, Secondary ; Macaca mulatta ; Male ; SAIDS Vaccines/*immunology ; Simian Acquired Immunodeficiency Syndrome/*prevention & control ; Simian Immunodeficiency Virus/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
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    Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus (2016)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2016-09-02
    Description: HIV-1–specific broadly neutralizing antibodies (bNAbs) can protect rhesus monkeys against simian-human immunodeficiency virus (SHIV) challenge. However, the site of antibody interception of virus and the mechanism of antibody-mediated protection remain unclear. We administered a fully protective dose of the bNAb PGT121 to rhesus monkeys and challenged them intravaginally with SHIV-SF162P3. In PGT121-treated animals, we detected low levels of viral RNA and viral DNA in distal tissues for seven days following challenge. Viral RNA–positive tissues showed transcriptomic changes indicative of innate immune activation, and cells from these tissues initiated infection after adoptive transfer into naïve hosts. These data demonstrate that bNAb-mediated protection against a mucosal virus challenge can involve clearance of infectious virus in distal tissues.
    Keywords: Immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 5
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    NS1 DNA vaccination protects against Zika infection through T cell-mediated immunity in immunocompetent mice (2019)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2019
    Description: 〈p〉The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell–based ZIKV vaccines.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 6
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    Lack of therapeutic efficacy of an antibody to {alpha}4{beta}7 in SIVmac251-infected rhesus macaques (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Sustained virologic control of human immunodeficiency virus type 1 (HIV-1) infection after discontinuation of antiretroviral therapy (ART) is a major goal of the HIV-1 cure field. A recent study reported that administration of an antibody against α〈sub〉4〈/sub〉β〈sub〉7〈/sub〉 induced durable virologic control after ART discontinuation in 100% of rhesus macaques infected with an attenuated strain of simian immunodeficiency virus (SIV) containing a stop codon in 〈i〉nef〈/i〉. We performed similar studies in 50 rhesus macaques infected with wild-type, pathogenic SIVmac251. In animals that initiated ART during either acute or chronic infection, anti-α〈sub〉4〈/sub〉β〈sub〉7〈/sub〉 antibody infusion had no detectable effect on the viral reservoir or viral rebound after ART discontinuation. These data demonstrate that anti-α〈sub〉4〈/sub〉β〈sub〉7〈/sub〉 antibody administration did not provide therapeutic efficacy in the model of pathogenic SIVmac251 infection of rhesus macaques.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    NS1 DNA vaccination protects against Zika infection through T cell–mediated immunity in immunocompetent mice (2019)
    American Association for the Advancement of Science
    Details
    Publication Date: 2019-12-04
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science
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