A vaccine against CCR5 protects a subset of macaques upon intravaginal challenge with simian immunodeficiency virus SIVmac251

Journal of Virology

Volumn 88, Issue 4, 2014, Pages 2011-2024

  Van Rompay, Koen K A ^a   Hunter, Zoe ^b   Jayashankar, Kartika ^a   Peabody, Julianne ^b   Montefiori, David ^c   LaBranche, Celia C ^c   Keele, Brandon F ^d   Jensen, Kara ^e   Abel, Kristina ^e   Chackerian, Bryce ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF NEW MEXICO SCHOOL OF MEDICINE   (United States)

^c DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH   (United States)

^e UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADMINISTRATION, INTRAVAGINAL; ALLOLEVIVIRUS; AMINO ACID SEQUENCE; ANIMALS; IMMUNOGLOBULIN G; MACACA MULATTA; MOLECULAR SEQUENCE DATA; PEPTIDES; RECEPTORS, CCR5; RNA, VIRAL; SIMIAN IMMUNODEFICIENCY VIRUS; VIRAL LOAD; VIRAL VACCINES; VIRUS REPLICATION;

EID: 84893458479     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.02447-13     Document Type: Article

References (68)

1. Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA. 1996. CC CKR5: a Rantes, MIP-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 272:1955-1958. http://dx.doi.org/10.1126/science.272.5270.1955.
2. Deng HK, Unutmaz D, Kewalramani VN, Littman DR. 1997. Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 388:296-300. http://dx.doi.org/10.1038/40894.
3. Doranz BJ, Rucker J, Yi Y, Smyth RJ, Samson M, Peiper SC, Parmentier M, Collman RG, Doms RW. 1996. A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 85:1149-1158. http://dx.doi.org/10.1016/S0092-8674(00)81314-8.
4. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM. 2008. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc. Natl. Acad. Sci. U.S.A. 105:7552-7557. http://dx.doi.org/10.1073/pnas.0802203105.
5. Li S, Juarez J, Alali M, Dwyer D, Collman R, Cunningham A, Naif HM. 1999. Persistent CCR5 utilization and enhanced macrophage tropism by primary blood human immunodeficiency virus type 1 isolates from advanced stages of disease and comparison to tissue-derived isolates. J. Virol. 73:9741-9755.
6. Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, Macdonald ME, Stuhlmann H, Koup RA, Landau NR. 1996. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiplyexposed individuals to HIV-1 infection. Cell 86:367-377. http://dx.doi.org/10.1016/S0092-8674(00)80110-5.
7. Samson M, Libert F, Doranz BJ, Rucker J, Liesnard C, Farber CM, Saragosti S, Lapoumeroulie C, Cognaux J, Forceille C, Muyldermans G, Verhofstede C, Burtonboy G, Georges M, Imai T, Rana S, Yi Y, Smyth RJ, Collman RG, Doms RW, Vassart G, Parmentier M. 1996. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382:722-725. http://dx.doi.org/10.1038/382722a0.
8. Fätkenheuer G, Pozniak AL, Johnson MA, Plettenberg A, Staszewski S, Hoepelman AI, Saag MS, Goebel FD, Rockstroh JK, Dezube BJ, Jenkins TM, Medhurst C, Sullivan JF, Ridgway C, Abel S, James IT, Youle M, Van Der Ryst E. 2005. Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1. Nat. Med. 11:1170-1172. http://dx.doi.org/10.1038/nm1319.
9. Hunt JS, Romanelli F. 2009. Maraviroc, a CCR5 coreceptor antagonist that blocks entry of human immunodeficiency virus type 1. Pharmacotherapy 29:295-304. http://dx.doi.org/10.1592/phco.29.3.295.
10. Yost R, Pasquale TR, Sahloff EG. 2009. Maraviroc: a coreceptor CCR5 antagonist for management of HIV infection. Am. J. Health Syst. Pharm. 66:715-726. http://dx.doi.org/10.2146/ajhp080206.
11. Jacobson JM, Lalezari JP, Thompson MA, Fichtenbaum CJ, Saag MS, Zingman BS, D'ambrosio P, Stambler N, Rotshteyn Y, Marozsan AJ, Maddon PJ, Morris SA, Olson WC. 2010. Phase 2a study of the CCR5 monoclonal antibody PRO 140 administered intravenously to HIVinfected adults. Antimicrob. Agents Chemother. 54:4137-4142. http://dx.doi.org/10.1128/AAC.00086-10.
12. Jacobson JM, Thompson MA, Lalezari JP, Saag MS, Zingman BS, D'ambrosio P, Stambler N, Rotshteyn Y, Marozsan AJ, Maddon PJ, Morris SA, Olson WC. 2010. Anti-HIV-1 activity of weekly or biweekly treatment with subcutaneous PRO 140, a CCR5 monoclonal antibody. J. Infect. Dis. 201:1481-1487. http://dx.doi.org/10.1086/652190.
13. Chackerian B, Briglio L, Albert PS, Lowy DR, Schiller JT. 2004. Induction of autoantibodies to CCR5 in macaques and subsequent effects upon challenge with an R5-tropic simian/human immunodeficiency virus. J. Virol. 78: 4037-4047. http://dx.doi.org/10.1128/JVI.78.8.4037-4047.2004.
14. Chackerian B, Lowy DR, Schiller JT. 1999. Induction of autoantibodies to mouse CCR5 with recombinant papillomavirus particles. Proc. Natl. Acad. Sci. U.S.A. 96:2373-2378. http://dx.doi.org/10.1073/pnas.96.5.2373.
15. Chackerian B, Lowy DR, Schiller JT. 2001. Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies. J. Clin. Invest. 108:415-423. http://dx.doi.org/10.1172/JCI11849.
16. Chackerian B, Durfee MR, Schiller JT. 2008. Virus-like display of a neo-self antigen reverses B cell anergy in a B cell receptor transgenic mouse model. J. Immunol. 180:5816-5825.
17. Chackerian B, Lenz P, Lowy DR, Schiller JT. 2002. Determinants of autoantibody induction by conjugated papillomavirus virus-like particles. J. Immunol. 169:6120-6126.
18. Chackerian B, Rangel M, Hunter Z, Peabody DS. 2006. Virus and virus-like particle-based immunogens for Alzheimer's disease induce antibody responses against amyloid-beta without concomitant T cell responses. Vaccine 24:6321-6331. http://dx.doi.org/10.1016/j.vaccine.2006.05.059.
19. Misumi S, Nakayama D, Kusaba M, Iiboshi T, Mukai R, Tachibana K, Nakasone T, Umeda M, Shibata H, Endo M, Takamune N, Shoji S. 2006. Effects of immunization with CCR5-based cycloimmunogen on simian/HIVSF162P3 challenge. J. Immunol. 176:463-471.
20. Zuber B, Hinkula J, Vodros D, Lundholm P, Nilsson C, Morner A, Levi M, Benthin R, Wahren B. 2000. Induction of immune responses and break of tolerance by DNA against the HIV-1 coreceptor CCR5 but no protection from SIVsm challenge. Virology 278:400-411. http://dx.doi.org/10.1006/viro.2000.0633.
21. Bogers WM, Bergmeier LA, Ma J, Oostermeijer H, Wang Y, Kelly CG, Ten Haaft P, Singh M, Heeney JL, Lehner T. 2004. A novel HIV-CCR5 receptor vaccine strategy in the control of mucosal SIV/HIV infection. AIDS 18:25-36. http://dx.doi.org/10.1097/00002030-200401020-00003.
22. Barassi C, Soprana E, Pastori C, Longhi R, Buratti E, Lillo F, Marenzi C, Lazzarin A, Siccardi AG, Lopalco L. 2005. Induction of murine mucosal CCR5-reactive antibodies as an anti-human immunodeficiency virus strategy. J. Virol. 79:6848-6858. http://dx.doi.org/10.1128/JVI.79.11.6848-6858.2005.
23. Chain BM, Noursadeghi M, Gardener M, Tsang J, Wright E. 2008. HIV blocking antibodies following immunisation with chimaeric peptides coding a short N-terminal sequence of the CCR5 receptor. Vaccine 26: 5752-5759. http://dx.doi.org/10.1016/j.vaccine.2008.08.025.
24. Hunter Z, Smyth HD, Durfee P, Chackerian B. 2009. Induction of mucosal and systemic antibody responses against the HIV coreceptor CCR5 upon intramuscular immunization and aerosol delivery of a viruslike particle based vaccine. Vaccine 28:403-414. http://dx.doi.org/10.1016/j.vaccine.2009.10.035.
25. Sina ST, Ren W, Cheng-Mayer C. 2011. Coreceptor use in nonhuman primate models of HIV infection. J. Transl. Med. 9(Suppl 1):S7.
26. Veazey RS, Ketas TJ, Dufour J, Moroney-Rasmussen T, Green LC, Klasse PJ, Moore JP. 2010. Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor. J. Infect. Dis. 202:739-744. http://dx.doi.org/10.1086/655661.
27. National Research Council. 1996. Guide for the care and use of laboratory animals. National Academy Press, Washington, DC.
28. Marthas ML, Lu DL, Penedo MCT, Hendrickx AG, Miller CJ. 2001. Titration of an SIVmac251 stock by vaginal inoculation of Indian and Chinese origin rhesus macaques: transmission efficiency, viral loads, and antibody responses. AIDS Res. Hum. Retroviruses 17:1455-1466. http://dx.doi.org/10.1089/088922201753197123.
29. Miller CJ, Li Q, Abel K, Kim EY, Ma ZM, Wietgrefe S, La Franco-Scheuch L, Compton L, Duan L, Shore MD, Zupancic M, Busch M, Carlis J, Wolinsky S, Haase AT. 2005. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J. Virol. 79: 9217-9227. http://dx.doi.org/10.1128/JVI.79.14.9217-9227.2005.
30. Marthas ML, Van Rompay KK, Abbott Z, Earl P, Buonocore-Buzzelli L, Moss B, Rose NF, Rose JK, Kozlowski PA, Abel K. 2011. Partial efficacy of a VSV-SIV/MVA-SIV vaccine regimen against oral SIV challenge in infant macaques. Vaccine 29:3124-3137. http://dx.doi.org/10.1016/j.vaccine.2011.02.051.
31. + cell-mediated suppression of virulent simian immunodeficiency virus during tenofovir treatment. J. Virol. 78:5324-5337. http://dx.doi.org/10.1128/JVI.78.10.5324-5337.2004.
32. Van Rompay KK, Trott KA, Jayashankar K, Geng Y, Labranche CC, Johnson JA, Landucci G, Lipscomb J, Tarara RP, Canfield DR, Heneine W, Forthal DN, Montefiori D, Abel K. 2012. Prolonged tenofovir treatment of macaques infected with K65R reverse transcriptase mutants of SIV results in the development of antiviral immune responses that control virus replication after drug withdrawal. Retrovirology 9:57. http://dx.doi.org/10.1186/1742-4690-9-57.
33. + T cells to gut-associated lymphoid tissue during chronic infection. J. Virol. 77:5621-5631. http://dx.doi.org/10.1128/JVI.77.10.5621-5631.2003.
34. + T cell epitopes. Immunogenetics 59:693-703. http://dx.doi.org/10.1007/s00251-007-0233-7.
35. Loffredo JT, Maxwell J, Qi Y, Glidden CE, Borchardt GJ, Soma T, Bean AT, Beal DR, Wilson NA, Rehrauer WM, Lifson JD, Carrington M, Watkins DI. 2007. Mamu-B&z.ast;08-positive macaques control simian immu-nodeficiency virus replication. J. Virol. 81:8827-8832. http://dx.doi.org/10.1128/JVI.00895-07.
36. Fenizia C, Keele BF, Nichols D, Cornara S, Binello N, Vaccari M, Pegu P, Robert-Guroff M, Ma ZM, Miller CJ, Venzon D, Hirsch V, Franchini G. 2011. TRIM5alpha does not affect simian immunodeficiency virus SIV(mac251) replication in vaccinated or unvaccinated Indian rhesus macaques following intrarectal challenge exposure. J. Virol. 85:12399-12409. http://dx.doi.org/10.1128/JVI.05707-11.
37. Cline AN, Bess JW, Piatak M, Jr, Lifson JD. 2005. Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS. J. Med. Primatol. 34:303-312. http://dx.doi.org/10.1111/j.1600-0684.2005.00128.x.
38. Venneti S, Bonneh-Barkay D, Lopresti BJ, Bissel SJ, Wang G, Mathis CA, Piatak M, Jr, Lifson JD, Nyaundi JO, Murphey-Corb M, Wiley CA. 2008. Longitudinal in vivo positron emission tomography imaging of infected and activated brain macrophages in a macaque model of human immunodeficiency virus encephalitis correlates with central and peripheral markers of encephalitis and areas of synaptic degeneration. Am. J. Pathol. 172:1603-1616. http://dx.doi.org/10.2353/ajpath.2008.070967.
39. Van Rompay KKA, Marthas ML, Ramos RA, Mandell CP, Mcgowan EK, Joye SM, Pedersen NC. 1992. Simian immunodeficiency virus (SIV) infection of infant rhesus macaques as a model to test antiretroviral drug prophylaxis and therapy: oral 3'-azido-3'-deoxythymidine prevents SIV infection. Antimicrob. Agents Chemother. 36:2381-2386. http://dx.doi.org/10.1128/AAC.36.11.2381.
40. Van Rompay KKA, Singh R, Brignolo L, Lawson JR, Schmidt KA, Pahar B, Canfield DR, Tarara RP, Bischofberger N, Marthas M. 2004. The clinical benefits of tenofovir for simian immunodeficiency virus-infected macaques are larger than predicted by its effects on standard viral and immunological parameters. J. Acquir. Immune Defic. Syndr. 36:900-914. http://dx.doi.org/10.1097/00126334-200408010-00003.
41. Montefiori DC. 2004. Evaluating neutralizing antibodies against HIV, SIV and SHIV in luciferase reporter gene assays. Curr. Protoc. Immunol. 64:12.11.1-12.11.17. http://dx.doi.org/10.1002/0471142735.im1211s64.
42. Li M, Gao F, Mascola JR, Stamatatos L, Polonis VR, Koutsoukos M, Voss G, Goepfert P, Gilbert P, Greene KM, Bilska M, Kothe DL, Salazar-Gonzalez JF, Wei X, Decker JM, Hahn BH, Montefiori DC. 2005. Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol. 79:10108-10125. http://dx.doi.org/10.1128/JVI.79.16.10108-10125.2005.
43. Wu L, Larosa G, Kassam N, Gordon CJ, Heath H, Ruffing N, Chen H, Humblias J, Samson M, Parmentier M, Moore JP, Mackay CR. 1997. Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding. J. Exp. Med. 186:1373-1381. http://dx.doi.org/10.1084/jem.186.8.1373.
44. Edinger AL, Amedee A, Miller K, Doranz BJ, Endres M, Sharron M, Samson M, Lu ZH, Clements JE, Murphey-Corb M, Peiper SC, Parmentier M, Broder CC, Doms RW. 1997. Differential utilization of CCR5 by macrophage and T cell tropic simian immunodeficiency virus strains. Proc. Natl. Acad. Sci. U.S.A. 94:4005-4010. http://dx.doi.org/10.1073/pnas.94.8.4005.
45. Farzadegan H, Henrard DR, Kleeberger CA, Schrager L, Kirby AJ, Saah AJ, Rinaldo CR, Jr, O'Gorman M, Detels R, Taylor E, Phair JP, Margolick JB. 1996. Virologic and serologic markers of rapid progression to AIDS after HIV-1 seroconversion. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 13:448-455. http://dx.doi.org/10.1097/00042560-199612150-00008.
46. Misumi S, Nakajima R, Takamune N, Shoji S. 2001. A cyclic dodecapeptide-multiple-antigen peptide conjugate from the undecapeptidyl arch (from Arg(168) to Cys(178)) of extracellular loop 2 in CCR5 as a novel human immunodeficiency virus type 1 vaccine. J. Virol. 75:11614-11620. http://dx.doi.org/10.1128/JVI.75.23.11614-11620.2001.
47. Hunter Z, Tumban E, Dziduszko A, Chackerian B. 2011. Aerosol delivery of virus-like particles to the genital tract induces local and systemic antibody responses. Vaccine 29:4584-4592. http://dx.doi.org/10.1016/j.vaccine.2011.04.051.
48. Choudhry V, Zhang MY, Harris I, Sidorov IA, Vu B, Dimitrov AS, Fouts T, Dimitrov DS. 2006. Increased efficacy of HIV-1 neutralization by antibodies at low CCR5 surface concentration. Biochem. Biophys. Res. Commun. 348:1107-1115. http://dx.doi.org/10.1016/j.bbrc.2006.07.163.
49. Dykhuizen M, Mitchen JL, Montefiori DC, Thomson J, Acker L, Lardy H, Pauza CD. 1998. Determinants of disease in the simian immunodeficiency virus-infected rhesus macaque: characterizing animals with low antibody responses and rapid progression. J. Gen. Virol. 79(Pt 10):2461-2467.
50. Smith SM, Holland B, Russo C, Dailey PJ, Marx PA, Connor RI. 1999. Retrospective analysis of viral load and SIV antibody responses in rhesus macaques infected with pathogenic SIV: predictive value for disease progression. AIDS Res. Hum. Retroviruses 15:1691-1701. http://dx.doi.org/10.1089/088922299309739.
51. Ma ZM, Keele BF, Qureshi H, Stone M, Desilva V, Fritts L, Lifson JD, Miller CJ. 6 July 2011. SIVmac251 is inefficiently transmitted to rhesus macaques by penile inoculation with a single SIVenv variant found in ramp-up phase plasma. AIDS Res. Hum. Retroviruses http://dx.doi.org/10.1089/aid.2011.0090.
52. Boyer JD, Kumar S, Robinson T, Parkinson R, Wu L, Lewis M, Watkins DI, Weiner DB. 2006. Initiation of antiretroviral therapy during chronic SIV infection leads to rapid reduction in viral loads and the level of T-cell immune response. J. Med. Primatol. 35:202-209. http://dx.doi.org/10.1111/j.1600-0684.2006.00179.x.
53. Yant LJ, Friedrich TC, Johnson RC, May GE, Maness NJ, Enz AM, Lifson JD, O'Connor DH, Carrington M, Watkins DI. 2006. The highfrequency major histocompatibility complex class I allele Mamu-B&z.ast;17 is associated with control of simian immunodeficiency virus SIVmac239 replication. J. Virol. 80:5074-5077. http://dx.doi.org/10.1128/JVI.80.10.5074-5077.2006.
54. Mothé BR, Weinfurter J, Wang C, Rehrauer W, Wilson N, Allen TM, Allison DB, Watkins DI. 2003. Expression of the major histocompatibility complex class I molecule Mamu-A&z.ast;01 is associated with control of simian immunodeficiency virus SIVmac239 replication. J. Virol. 77:2736-2740. http://dx.doi.org/10.1128/JVI.77.4.2736-2740.2003.
55. Lifson JD, Rossion JL, Piatak MJ, Parks T, Li L, Kiser R, Coalter V, Fisher B, Flynn BM, Czajak S, Hirsch VM, Reimann KA, Schmitz JE, Ghrayeb J, Bischofberger N, Nowak MA, Desrosiers RC, Wodarz D. 2001. Role of CD8+ lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment. J. Virol. 75:10187-10199. http://dx.doi.org/10.1128/JVI.75.21.10187-10199.2001.
56. Van Rompay KK, Johnson JA, Blackwood EJ, Singh RP, Lipscomb J, Matthews TB, Marthas ML, Pedersen NC, Bischofberger N, Heneine W, North TW. 2007. Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RTSHIV infection. Retrovirology 4:25. http://dx.doi.org/10.1186/1742-4690-4-25.
57. Glass WG, McDermott DH, Lim JK, Lekhong S, Yu SF, Frank WA, Pape J, Cheshier RC, Murphy PM. 2006. CCR5 deficiency increases risk of symptomatic West Nile virus infection. J. Exp. Med. 203:35-40. http://dx.doi.org/10.1084/jem.20051970.
58. Kindberg E, Mickiene A, Ax C, Akerlind B, Vene S, Lindquist L, Lundkvist A, Svensson L. 2008. A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis. J. Infect. Dis. 197: 266-269. http://dx.doi.org/10.1086/524709.
59. Lalezari J, Yadavalli GK, Para M, Richmond G, Dejesus E, Brown SJ, Cai W, Chen C, Zhong J, Novello LA, Lederman MM, Subramanian GM. 2008. Safety, pharmacokinetics, and antiviral activity of HGS004, a novel fully human IgG4 monoclonal antibody against CCR5, in HIV-1-infected patients. J. Infect. Dis. 197:721-727. http://dx.doi.org/10.1086/527327.
60. Recordon-Pinson P, Raymond S, Bellecave P, Marcelin AG, Soulie C, Descamps D, Calvez V, Harrigan PR, Fleury H, Izopet J, Masquelier B; S AC11 Resistance Study Group. 2013. HIV-1 dynamics and coreceptor usage in Maraviroc-treated patients with ongoing replication. Antimicrob. Agents Chemother. 57:930-935. http://dx.doi.org/10.1128/AAC.02159-12.
61. Lee B, Sharron M, Montaner LJ, Weissman D, Doms RW. 1999. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc. Natl. Acad. Sci. U.S.A. 96:5215-5220. http://dx.doi.org/10.1073/pnas.96.9.5215.
62. Zhang J, Rao E, Dioszegi M, Kondru R, Derosier A, Chan E, Schwoerer S, Cammack N, Brandt M, Sankuratri S, Ji C. 2007. The second extracellular loop of CCR5 contains the dominant epitopes for highly potent anti-human immunodeficiency virus monoclonal antibodies. Antimicrob. Agents Chemother. 51:1386-1397. http://dx.doi.org/10.1128/AAC.01302-06.
63. Marthas ML, Ramos RA, Lohman BL, Van Rompay KKA, Unger RE, Miller CJ, Banapour B, Pedersen NC, Luciw PA. 1993. Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac. J. Virol. 67:6047-6055.
64. Marthas ML, Banapour B, Sutjipto S, Siegel ME, Marx PA, Gardner MB, Pedersen NC, Luciw PA. 1989. Rhesus macaques inoculated with molecularly cloned simian immunodeficiency virus. J. Med. Primatol. 18:311-319.
65. Van Rompay KK, Blackwood EJ, Landucci G, Forthal D, Marthas ML. 2006. Role of CD8+ Cells in controlling replication of nonpathogenic simian immunodeficiency virus SIVmac1A11. Virol. J. 3:22. http://dx.doi.org/10.1186/1743-422X-3-22.
66. Van Rompay KKA, Mcchesney MB, Aguirre NL, Schmidt KA, Bischofberger N, Marthas ML. 2001. Two low doses of tenofovir protect newborn macaques against oral simian immunodeficiency virus infection. J. Infect. Dis. 184:429-438. http://dx.doi.org/10.1086/322781.
67. Van Rompay KKA, Marthas ML, Lifson JD, Berardi CJ, Vasquez GM, Agatep E, Dehqanzada ZA, Cundy KC, Bischofberger N, Pedersen NC. 1998. Administration of 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) for prevention of perinatal simian immunodeficiency virus infection in rhesus macaques. AIDS Res. Hum. Retroviruses 14:761-773. http://dx.doi.org/10.1089/aid.1998.14.761.
68. Regoes RR, Longini IM, Feinberg MB, Staprans SI. 2005. Preclinical assessment of HIV vaccines and microbicides by repeated low-dose virus challenges. PLoS Med. 2:e249. http://dx.doi.org/10.1371/journal.pmed.0020249.