Multiprotein HIV type 1 clade B DNA/MVA vaccine: construction, safety, and immunogenicity in Macaques

AIDS Research and Human Retroviruses
James M SmithHarriet L Robinson

Abstract

Recently, a simian/human immunodeficiency virus (SHIV) vaccine consisting of priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia Ankara (rMVA) has successfully controlled a virulent SHIV challenge in a macaque model. In this, and the accompanying paper, we report on the construction and testing of a Gag-Pol-Env DNA/MVA vaccine for HIV-1/AIDS. The DNA vaccine, pGA2/JS2, expresses aggregates of Gag proteins and includes safety mutations that render it integration, reverse transcription, and packaging defective. The rMVA vaccine, MVA/HIV 48, is integration and reverse transcription defective and has a truncated Env to enhance expression on the plasma membrane. In a study in rhesus macaques, priming with pGA2/JS2 and boosting with MVA/HIV 48 raised high frequencies of T cells for Gag and Env and lower frequencies of T cells for PR, RT, and Tat. Stimulations with five peptide pools for Gag and seven peptide pools for Env revealed epitopes for cellular immune responses throughout Gag and Env. On average, CD4 T cells from the vaccinated animals recognized 7.1 peptide pools and CD8 T cells, 3.2 peptide pools. Both the height and the breadth of the elicited cellular response...Continue Reading

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Citations

Mar 9, 2006·Current HIV/AIDS Reports·Isaac R Rodriguez-ChavezM Patricia D'Souza
Apr 7, 2005·Nature Medicine·Harriet L Robinson, Rama Rao Amara
Jul 13, 2006·AIDS Research and Human Retroviruses·M J MulliganUNKNOWN NIH/NIAID/DAIDS HIV Vaccine Trials Network
Feb 2, 2011·The Journal of Infectious Diseases·Paul A GoepfertUNKNOWN National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network
Jan 10, 2014·The Journal of Infectious Diseases·Paul A GoepfertUNKNOWN National Institutes of Allergy and Infectious Diseases HIV Vaccines Trials Network
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Oct 16, 2004·Reviews in Medical Virology·Linh X DoanQizhi Yao
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Jul 25, 2013·Human Vaccines & Immunotherapeutics·Maria IsaguliantsElizaveta Starodubova
Nov 1, 2012·Human Vaccines & Immunotherapeutics·Michael HellersteinHarriet L Robinson
Oct 1, 2010·Critical Reviews in Biotechnology·Clarence M OngkudonMichael K Danquah
Nov 16, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sunil KannanganatRama Rao Amara
Aug 26, 2017·Expert Review of Vaccines·Lynette Siv Chea, Rama Rao Amara
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Aug 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jin Hyang KimJoshy Jacob

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