RV144 remains the only HIV-1 vaccine trial to demonstrate efficacy against HIV-1 acquisition. The prespecified analysis of immune correlates of risk showed that antibodies directed against the V1V2 region of gp120, in particular the IgG1 and IgG3 subclass mediating antibody-dependent cell-mediated cytotoxicity, seem to play a predominant role in protection against HIV-1 acquisition and that plasma envelope (Env)-specific IgA antibodies were directly correlated with risk. RV144 and recent nonhuman primate challenge studies suggest that Env is essential, and perhaps sufficient, to induce protective antibody responses against mucosal HIV-1 acquisition. Follow-up clinical trials are ongoing to further dissect the immune responses elicited by the RV144 ALVAC-HIV and AIDSVAX® B/E regimen. The study of gp120 Env immunogens and immune correlates of risk has resulted in the development of improved antigens. Whether the RV144 immune correlates of risk will generalize to other populations vaccinated with similar immunogens with different modes and intensity of transmission remains to be demonstrated. Efficacy trials are now planned in heterosexual populations in southern Africa and men who have sex with men in Thailand.


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Literature Cited

  1. 1. UNAIDS 2013. Report on the global AIDS epidemic http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/unaids_global_report_2013_en.pdf [Google Scholar]
  2. Nitayaphan S, Ngauy V, O'Connell R. 2.  et al. 2012. HIV epidemic in Asia: optimizing and expanding vaccine development. Expert Rev. Vaccines 11:805–19 [Google Scholar]
  3. Abdool Karim Q, Abdool Karim SS, Frohlich JA. 3.  et al. 2010. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329:1168–74 [Google Scholar]
  4. Grant RM, Lama JR, Anderson PL. 4.  et al. 2010. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 363:2587–99 [Google Scholar]
  5. Baeten JM, Donnell D, Ndase P. 5.  et al. 2012. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N. Engl. J. Med. 367:399–410 [Google Scholar]
  6. Choopanya K, Martin M, Suntharasamai P. 6.  et al. 2013. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 381:2083–90 [Google Scholar]
  7. Van Damme L, Corneli A, Ahmed K. 7.  et al. 2012. Preexposure prophylaxis for HIV infection among African women. N. Engl. J. Med. 367:411–22 [Google Scholar]
  8. Fauci AS, Marston HD. 8.  2014. Ending AIDS—Is an HIV vaccine necessary?. N. Engl. J. Med. 370:495–98 [Google Scholar]
  9. Haynes BF, McElrath MJ. 9.  2013. Progress in HIV-1 vaccine development. Curr. Opin. HIV AIDS 8:326–32 [Google Scholar]
  10. Hemelaar J, Gouws E, Ghys PD. 10.  et al. 2011. Global trends in molecular epidemiology of HIV-1 during 2000–2007. AIDS 25:679–89 [Google Scholar]
  11. McBurney SP, Ross TM. 11.  2008. Viral sequence diversity: challenges for AIDS vaccine designs. Expert Rev. Vaccines 7:1405–17 [Google Scholar]
  12. Moir S, Chun TW, Fauci AS. 12.  2011. Pathogenic mechanisms of HIV disease. Annu. Rev. Pathol. 6:223–48 [Google Scholar]
  13. Burton DR, Ahmed R, Barouch DH. 13.  et al. 2012. A blueprint for HIV vaccine discovery. Cell Host Microbe 12:396–407 [Google Scholar]
  14. Haynes BF, Kelsoe G, Harrison SC. 14.  et al. 2012. B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study. Nat. Biotechnol. 30:423–33 [Google Scholar]
  15. Plotkin SA, Gilbert PB. 15.  2012. Nomenclature for immune correlates of protection after vaccination. Clin. Infect. Dis. 54:1615–17 [Google Scholar]
  16. Plotkin SA.16.  2013. Complex correlates of protection after vaccination. Clin. Infect. Dis. 56:1458–65 [Google Scholar]
  17. Mascola JR.17.  2007. HIV/AIDS: allied responses. Nature 449:29–30 [Google Scholar]
  18. Burton DR, Hessell AJ, Keele BF. 18.  et al. 2011. Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody. Proc. Natl. Acad. Sci. USA 108:11181–86 [Google Scholar]
  19. Blankson JN.19.  2011. The study of elite controllers: a pure academic exercise or a potential pathway to an HIV-1 vaccine?. Curr. Opin. HIV AIDS 6:147–50 [Google Scholar]
  20. Berman PW, Gregory TJ, Riddle L. 20.  et al. 1990. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature 345:622–25 [Google Scholar]
  21. Girard M, Kieny MP, Pinter A. 21.  et al. 1991. Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 88:542–46 [Google Scholar]
  22. Flynn NM, Forthal DN, Harro CD. 22.  et al. 2005. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J. Infect. Dis. 191:654–65 [Google Scholar]
  23. Gilbert PB, Peterson ML, Follmann D. 23.  et al. 2005. Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 infection in a phase 3 HIV-1 preventive vaccine trial. J. Infect. Dis. 191:666–77 [Google Scholar]
  24. Pitisuttithum P, Gilbert P, Gurwith M. 24.  et al. 2006. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J. Infect. Dis. 194:1661–71 [Google Scholar]
  25. Buchbinder SP, Mehrotra DV, Duerr A. 25.  et al. 2008. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372:1881–93 [Google Scholar]
  26. McElrath MJ, De Rosa SC, Moodie Z. 26.  et al. 2008. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372:1894–905 [Google Scholar]
  27. Rolland M, Tovanabutra S, deCamp AC. 27.  et al. 2011. Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial. Nat. Med. 17:366–71 [Google Scholar]
  28. Fitzgerald DW, Janes H, Robertson M. 28.  et al. 2011. An Ad5-vectored HIV-1 vaccine elicits cell-mediated immunity but does not affect disease progression in HIV-1-infected male subjects: results from a randomized placebo-controlled trial (the Step study). J. Infect. Dis. 203:765–72 [Google Scholar]
  29. Li F, Finnefrock AC, Dubey SA. 29.  et al. 2011. Mapping HIV-1 vaccine induced T-cell responses: bias towards less-conserved regions and potential impact on vaccine efficacy in the Step study. PLOS ONE 6:e20479 [Google Scholar]
  30. Gray GE, Allen M, Moodie Z. 30.  et al. 2011. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect. Dis. 11:507–15 [Google Scholar]
  31. Duerr A, Huang Y, Buchbinder S. 31.  et al. 2012. Extended follow-up confirms early vaccine-enhanced risk of HIV acquisition and demonstrates waning effect over time among participants in a randomized trial of recombinant adenovirus HIV vaccine (Step Study). J. Infect. Dis. 206:258–66 [Google Scholar]
  32. Gray GE, Moodie Z, Metch B. 32.  et al. 2014. Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study. Lancet Infect. Dis. 14:388–96 [Google Scholar]
  33. Reynolds MR, Weiler AM, Piaskowski SM. 33.  et al. 2012. A trivalent recombinant Ad5 gag/pol/nef vaccine fails to protect rhesus macaques from infection or control virus replication after a limiting-dose heterologous SIV challenge. Vaccine 30:4465–75 [Google Scholar]
  34. Qureshi H, Ma ZM, Huang Y. 34.  et al. 2012. Low-dose penile SIVmac251 exposure of rhesus macaques infected with adenovirus type 5 (Ad5) and then immunized with a replication-defective Ad5-based SIV gag/pol/nef vaccine recapitulates the results of the phase IIb step trial of a similar HIV-1 vaccine. J. Virol. 86:2239–50 [Google Scholar]
  35. Hammer SM, Sobieszczyk ME, Janes H. 35.  et al. 2013. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N. Engl. J. Med. 369:2083–92 [Google Scholar]
  36. Letvin NL, Rao SS, Montefiori DC. 36.  et al. 2011. Immune and genetic correlates of vaccine protection against mucosal infection by SIV in monkeys. Sci. Transl. Med. 3:81ra36 [Google Scholar]
  37. Roederer M, Keele BF, Schmidt SD. 37.  et al. 2014. Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV. Nature 505:502–8 [Google Scholar]
  38. 38. Ministry of Public Health—Thai AIDS Vaccine Evaluation Group 2011. Screening and evaluation of potential volunteers for a phase III trial in Thailand of a candidate preventive HIV vaccine (RV148). Vaccine 29:4285–92 [Google Scholar]
  39. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S. 39.  et al. 2009. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361:2209–20 [Google Scholar]
  40. Robb ML, Rerks-Ngarm S, Nitayaphan S. 40.  et al. 2012. Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: a post-hoc analysis of the Thai phase 3 efficacy trial RV 144. Lancet Infect. Dis. 12:531–37 [Google Scholar]
  41. Rerks-Ngarm S, Paris RM, Chunsutthiwat S. 41.  et al. 2013. Extended evaluation of the virologic, immunologic, and clinical course of volunteers who acquired HIV-1 infection in a phase III vaccine trial of ALVAC-HIV and AIDSVAX B/E. J. Infect. Dis. 207:1195–205 [Google Scholar]
  42. Whitney JB, Luedemann C, Hraber P. 42.  et al. 2009. T-cell vaccination reduces simian immunodeficiency virus levels in semen. J. Virol. 83:10840–43 [Google Scholar]
  43. Letvin NL, Mascola JR, Sun Y. 43.  et al. 2006. Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science 312:1530–33 [Google Scholar]
  44. Plotkin SA.44.  2008. Vaccines: correlates of vaccine-induced immunity. Clin. Infect. Dis. 47:401–9 [Google Scholar]
  45. Forthal DN, Gilbert PB, Landucci G. 45.  et al. 2007. Recombinant gp120 vaccine-induced antibodies inhibit clinical strains of HIV-1 in the presence of Fc receptor-bearing effector cells and correlate inversely with HIV infection rate. J. Immunol. 178:6596–603 [Google Scholar]
  46. Gilbert P, Wang M, Wrin T. 46.  et al. 2010. Magnitude and breadth of a nonprotective neutralizing antibody response in an efficacy trial of a candidate HIV-1 gp120 vaccine. J. Infect. Dis. 202:595–605 [Google Scholar]
  47. Karnasuta C, Paris RM, Cox JH. 47.  et al. 2005. Antibody-dependent cell-mediated cytotoxic responses in participants enrolled in a phase I/II ALVAC-HIV/AIDSVAX B/E prime-boost HIV-1 vaccine trial in Thailand. Vaccine 23:2522–29 [Google Scholar]
  48. Nitayaphan S, Pitisuttithum P, Karnasuta C. 48.  et al. 2004. Safety and immunogenicity of an HIV subtype B and E prime-boost vaccine combination in HIV-negative Thai adults. J. Infect. Dis. 190:702–6 [Google Scholar]
  49. Haynes BF, Gilbert PB, McElrath MJ. 49.  et al. 2012. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 366:1275–86 [Google Scholar]
  50. Pinter A, Honnen WJ, Kayman SC. 50.  et al. 1998. Potent neutralization of primary HIV-1 isolates by antibodies directed against epitopes present in the V1/V2 domain of HIV-1 gp120. Vaccine 16:1803–11 [Google Scholar]
  51. Montefiori DC, Karnasuta C, Huang Y. 51.  et al. 2012. Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials. J. Infect. Dis. 206:431–41 [Google Scholar]
  52. Gottardo R, Bailer RT, Korber BT. 52.  et al. 2013. Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial. PLOS ONE 8:e75665 [Google Scholar]
  53. Zolla-Pazner S, deCamp AC, Cardozo T. 53.  et al. 2013. Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial. PLOS ONE 8:e53629 [Google Scholar]
  54. Alam SM, Liao HX, Tomaras GD. 54.  et al. 2013. Antigenicity and immunogenicity of RV144 vaccine AIDSVAX clade E envelope immunogen is enhanced by a gp120 N-terminal deletion. J. Virol. 87:1554–68 [Google Scholar]
  55. Berman PW, Gray AM, Wrin T. 55.  et al. 1997. Genetic and immunologic characterization of viruses infecting MN-rgp120-vaccinated volunteers. J. Infect. Dis. 176:384–97 [Google Scholar]
  56. Gilbert PB.56.  2001. Interpretability and robustness of sieve analysis models for assessing HIV strain variations in vaccine efficacy. Stat. Med. 20:263–79 [Google Scholar]
  57. Gilbert PB, Wu C, Jobes DV. 57.  2008. Genome scanning tests for comparing amino acid sequences between groups. Biometrics 64:198–207 [Google Scholar]
  58. Rolland M, Edlefsen PT, Larsen BB. 58.  et al. 2012. Increased HIV-1 vaccine efficacy against viruses with genetic signatures in Env V2. Nature 490:417–20 [Google Scholar]
  59. Zolla-Pazner S, Decamp A, Gilbert PB. 59.  et al. 2014. Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection. PLOS ONE 9:e87572 [Google Scholar]
  60. Karasavvas N, Billings E, Rao M. 60.  et al. 2012. The Thai phase III HIV type 1 vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120. AIDS Res. Hum. Retroviruses 28:1444–57 [Google Scholar]
  61. Bonsignori M, Pollara J, Moody MA. 61.  et al. 2012. Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J. Virol. 86:11521–32 [Google Scholar]
  62. Pollara J, Bonsignori M, Moody MA. 62.  et al. 2014. HIV-1 vaccine-induced C1 and V2 Env-specific antibodies synergize for increased antiviral activities. J. Virol. 88:7715–26 [Google Scholar]
  63. Liu P, Yates NL, Shen X. 63.  et al. 2013. Infectious virion capture by HIV-1 gp120-specific IgG from RV144 vaccinees. J. Virol. 87:7828–36 [Google Scholar]
  64. Rolland MEP, Edlefsen PT, Gottardo R. 64.  et al. 2013. Genetic and immunological evidence for a role of Env-V3 antibodies in the RV144 trial. AIDS Res. Hum. Retroviruses 29A168 [Google Scholar]
  65. Brusic V, Gottardo R, Kleinstein SH. 65.  et al. 2014. Computational resources for high-dimensional immune analysis from the Human Immunology Project Consortium. Nat. Biotechnol. 32:146–48 [Google Scholar]
  66. Griffiss JM, Goroff DK. 66.  1983. IgA blocks IgM and IgG-initiated immune lysis by separate molecular mechanisms. J. Immunol. 130:2882–85 [Google Scholar]
  67. Tomaras GD, Ferrari G, Shen X. 67.  et al. 2013. Vaccine-induced plasma IgA specific for the C1 region of the HIV-1 envelope blocks binding and effector function of IgG. Proc. Natl. Acad. Sci. USA 110:9019–24 [Google Scholar]
  68. Bar KJ, Li H, Chamberland A. 68.  et al. 2010. Wide variation in the multiplicity of HIV-1 infection among injection drug users. J. Virol. 84:6241–47 [Google Scholar]
  69. Yates NL, Liao HX, Fong Y. 69.  et al. 2014. Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci. Transl. Med. 6:228ra39 [Google Scholar]
  70. Roussilhon C, Oeuvray C, Muller-Graf C. 70.  et al. 2007. Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3. PLOS Med. 4:e320 [Google Scholar]
  71. Kam YW, Simarmata D, Chow A. 71.  et al. 2012. Early appearance of neutralizing immunoglobulin G3 antibodies is associated with chikungunya virus clearance and long-term clinical protection. J. Infect. Dis. 205:1147–54 [Google Scholar]
  72. Chung AW, Ghebremichael M, Robinson H. 72.  et al. 2014. Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines. Sci. Transl. Med. 6:228ra38 [Google Scholar]
  73. Teigler JE, Phogat S, Franchini G. 73.  et al. 2014. The canarypox virus vector ALVAC induces distinct cytokine responses compared to the vaccinia virus–based vectors MVA and NYVAC in rhesus monkeys. J. Virol. 88:1809–14 [Google Scholar]
  74. Gorse GJ, Patel GB, Mandava M. 74.  et al. 1999. MN and IIIB recombinant glycoprotein 120 vaccine-induced binding antibodies to native envelope glycoprotein of human immunodeficiency virus type 1 primary isolates. National Institute of Allergy and Infectious Disease AIDS Vaccine Evaluation Group. AIDS Res. Hum. Retroviruses 15:921–30 [Google Scholar]
  75. Banerjee K, Klasse PJ, Sanders RW. 75.  et al. 2010. IgG subclass profiles in infected HIV type 1 controllers and chronic progressors and in uninfected recipients of Env vaccines. AIDS Res. Hum. Retroviruses 26:445–58 [Google Scholar]
  76. Ljunggren K, Broliden PA, Morfeldt-Manson L. 76.  et al. 1988. IgG subclass response to HIV in relation to antibody-dependent cellular cytotoxicity at different clinical stages. Clin. Exp. Immunol. 73:343–47 [Google Scholar]
  77. Barouch DH, Liu J, Li H. 77.  et al. 2012. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature 482:89–93 [Google Scholar]
  78. Pegu P, Vaccari M, Gordon S. 78.  et al. 2013. Antibodies with high avidity to the gp120 envelope protein in protection from simian immunodeficiency virus SIV(mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial. J. Virol. 87:1708–19 [Google Scholar]
  79. Barouch DH, Stephenson KE, Borducchi EN. 79.  et al. 2013. Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell 155:531–39 [Google Scholar]
  80. Sagar M, Wu X, Lee S. 80.  et al. 2006. Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity. J. Virol. 80:9586–98 [Google Scholar]
  81. Kwong PD, Wyatt R, Robinson J. 81.  et al. 1998. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393:648–59 [Google Scholar]
  82. Rizzuto CD, Wyatt R, Hernandez-Ramos N. 82.  et al. 1998. A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280:1949–53 [Google Scholar]
  83. Arthos J, Cicala C, Martinelli E. 83.  et al. 2008. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat. Immunol. 9:301–9 [Google Scholar]
  84. Bonsignori M, Hwang KK, Chen X. 84.  et al. 2011. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J. Virol. 85:9998–10009 [Google Scholar]
  85. Pejchal R, Doores KJ, Walker LM. 85.  et al. 2011. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334:1097–103 [Google Scholar]
  86. Walker LM, Phogat SK, Chan-Hui PY. 86.  et al. 2009. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326:285–89 [Google Scholar]
  87. Benjelloun F, Lawrence P, Verrier B. 87.  et al. 2012. Role of human immunodeficiency virus type 1 envelope structure in the induction of broadly neutralizing antibodies. J. Virol. 86:13152–63 [Google Scholar]
  88. Hoot S, McGuire AT, Cohen KW. 88.  et al. 2013. Recombinant HIV envelope proteins fail to engage germline versions of anti-CD4bs bNAbs. PLOS Pathog. 9:e1003106 [Google Scholar]
  89. Burton DR, Poignard P, Stanfield RL. 89.  et al. 2012. Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses. Science 337:183–86 [Google Scholar]
  90. Thongcharoen P, Suriyanon V, Paris RM. 90.  et al. 2007. A phase 1/2 comparative vaccine trial of the safety and immunogenicity of a CRF01_AE (subtype E) candidate vaccine: ALVAC-HIV (vCP1521) prime with oligomeric gp160 (92TH023/LAI-DID) or bivalent gp120 (CM235/SF2) boost. J. Acquir. Immune Defic. Syndr. 46:48–55 [Google Scholar]
  91. Hansen SG, Vieville C, Whizin N. 91.  et al. 2009. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat. Med. 15:293–99 [Google Scholar]
  92. Ratto-Kim S, Loomis-Price LD, Aronson N. 92.  et al. 2003. Comparison between env-specific T-cell epitopic responses in HIV-1-uninfected adults immunized with combination of ALVAC-HIV(vCP205) plus or minus rgp160MN/LAI-2 and HIV-1-infected adults. J. Acquir. Immune Defic. Syndr. 32:9–17 [Google Scholar]
  93. de Souza MS, Ratto-Kim S, Chuenarom W. 93.  et al. 2012. The Thai phase III trial (RV144) vaccine regimen induces T cell responses that preferentially target epitopes within the V2 region of HIV-1 envelope. J. Immunol. 188:5166–76 [Google Scholar]
  94. Brehm MA, Shultz LD, Luban J. 94.  et al. 2013. Overcoming current limitations in humanized mouse research. J. Infect. Dis. 208:Suppl. 2S125–30 [Google Scholar]
  95. Danner R, Chaudhari SN, Rosenberger J. 95.  et al. 2011. Expression of HLA class II molecules in humanized NOD.Rag1KO.IL2RgcKO mice is critical for development and function of human T and B cells. PLOS ONE 6:e19826 [Google Scholar]
  96. Allam AF.96.  2014. Characterization of B- and T cells in the gut mucosa of humanized DRAG mice during HIV infection Presented at Keystone Symp. HIV Vaccines—Adaptive Immunity and Beyond, Banff, Alberta, Can. [Google Scholar]

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