MHC TYPING OF MACAQUES USED IN AIDS RESEARCH

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objectives: To offer MHC typing of the MHC class I and II loci for investigators working with macaques (Indian rhesus, Chinese rhesus and Cynomolgus). To adapt technologies for HLA typing to molecular typing of macaque (Indian rhesus, Chinese rhesus, and Cynomolgus) MHC class I and II. PROGRESS: The increased utility of various species of macaques as animal models in both HIV vaccine development and pathogenesis studies necessitates the continuation of reference MHC typing laboratories for these species. We plan to continue to offer services to both the North American and European scientific communities for MHC typing of macaques. Initially, this will include PCR-SSP tests for alleles encoding MHC class I and II molecules that bind peptides derived from SIV and SHIV. We are developing additional molecular techniques for analysis of the Indian rhesus, Chinese rhesus and Cynomolgus macaque MHC class I and class II alleles. Additionally, we offer training and materials to individual laboratories that wish to set up MHC typing. Finally, we are developing a panel of well-characterized cell lines that will be invaluable for the analysis of the MHC in the macaque. From 2002 to the present, we have performed more than 148,000 typings for more than 130 investigators at 50 institutions. In 2010, we conducted 22,400 typings at the request of 21 principal investigators from 17 different institutions. We have offered expanded Class II typing services during 2010. This research used WNPRC Animal, Immunogenetics, and Pathology & Virology services. PUBLICATIONS: Doxiadis GG, de Groot N, de Groot NG, Rotmans G, de Vos-Rouweler AJ, Bontrop RE. Immunogenetics. Extensive DRB region diversity in cynomolgus macaques: recombination as a driving force. Immunogenetics. 2010 Mar; 62(3):137-47. Epub 2010 Feb 4. PMID: 20131048, PMCID: PMC2827794. Casimiro DR, Cox K, Tang A, Sykes KJ, Feng M, Wang F, Bett A, Schleif WA, Liang X, Flynn J, Tobery TW, Wilson K, Finnefrock A, Huang L, Vitelli S, Lin J, Patel D, Davies ME, Heidecker GJ, Freed DC, Dubey S, O'Connor DH, Watkins DI, Zhang ZQ, Shiver JW. Efficacy of multivalent adenovirus-based vaccine against simian immunodeficiency virus challenge. J Virol. 2010 Mar; 84(6):2996-3003. Epub 2009 Dec 30. PMID: 20042509, PMCID: PMC2826028. Martins MA, Wilson NA, Reed JS, Ahn CD, Klimentidis YC, Allison DB, Watkins DI. T-cell correlates of vaccine efficacy after a heterologous simian immunodeficiency virus challenge. J Virol. 2010 May; 84(9):4352-65. Epub 2010 Feb 17. PMID: 20164222, PCMID: PMC2863752. Mudd PA, Piaskowski SM, Neves PC, Rudersdorf R, Kolar HL, Eernisse CM, Weisgrau KL, de Santana MG, Wilson NA, Bonaldo MC, Galler R, Rakasz EG, Watkins DI. The live-attenuated yellow fever vaccine 17D induces broad and potent T cell responses against several viral proteins in Indian rhesus macaques--implications for recombinant vaccine design. Immunogenetics. 2010 Sep; 62(9):593-600. Epub 2010 Jul 7. PMID: 20607226, PMCID: PMC Journal in Process. Reynolds MR, Weiler AM, Piaskowski SM, Kolar HL, Hessell AJ, Weiker M, Weisgrau KL, Le¿n EJ, Rogers WE, Makowsky R, McDermott AB, Boyle R, Wilson NA, Allison DB, Burton DR, Koff WC, Watkins DI. Macaques vaccinated with simian immunodeficiency virus SIVmac239Delta nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge. J Virol. 2010 Sep; 84(18):9190-9. Epub 2010 Jun 30. PMID: 20592091, PMCID: PMC2937616. Giraldo-Vela JP, Bean AT, Rudersdorf R, Wallace LT, Loffredo JT, Erickson P, Wilson NA, Watkins DI. Simian immunodeficiency virus-specific CD4+ T cells from successful vaccinees target the SIV Gag capsid. Immunogenetics. 2010 Oct; 62(10):701-7. Epub 2010 Sep 2. PMID: 20812010, PMCID: PMC3018234. Maness NJ, Walsh AD, Piaskowski SM, Furlott J, Kolar HL, Bean AT, Wilson NA, Watkins DI. CD8+ T cell recognition of cryptic epitopes is a ubiquitous feature of AIDS virus infection. J Virol. 2010 Nov; 84(21):11569-74. Epub 2010 Aug 25. Erratum in: J Virol. 2011 Jan; 85(1):649. PMID: 20739530, PMCID: PMC2953171.