Current views on the potential for development of a HIV vaccine

Expert Opinion on Biological Therapy

Volumn 17, Issue 3, 2017, Pages 295-303

  Cohen, Kristen W ^a   Frahm, Nicole ^a,b  

^a Fred Hutchinson Cancer Research Center   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

broadly neutralizing antibodies; efficacy trial; HIV vaccine; polyfunctional antibodies; T cell based vaccine

Indexed keywords

CD4 ANTIGEN; CD8 ANTIGEN; ERDOSTEINE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; NEUTRALIZING ANTIBODY; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY;

ANTIBODY RESPONSE; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DRUG EFFICACY; FOLLOW UP; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE; IMMUNIZATION; INFECTION RATE; NONHUMAN; REVIEW; SIMIAN IMMUNODEFICIENCY VIRUS; T LYMPHOCYTE; ANIMAL; GENETICS; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; PHYSIOLOGY; VIROLOGY;

AIDS VACCINES; ANIMALS; ANTIBODIES, NEUTRALIZING; HIV ANTIBODIES; HIV INFECTIONS; HIV-1; HUMANS;

EID: 85012964539     PISSN: 14712598     EISSN: 17447682     Source Type: Journal    
DOI: 10.1080/14712598.2017.1282457     Document Type: Review

References (101)

1. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493–505.
2. Auvert B, Taljaard D, Lagarde E, et al. Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk:the ANRS 1265 trial. Plos Med. 2005 Nov;2(11):e298.
3. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya:a randomised controlled trial. Lancet. 2007 Feb 24;369(9562):643–656.
4. Gray RH, Kigozi G, Serwadda D, et al. Male circumcision for HIV prevention in men in Rakai, Uganda:a randomised trial. Lancet. 2007 Feb 24;369(9562):657–666.
5. Abdool Karim Q, Abdool Karim SS, Frohlich JA, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010 Sep 3;329(5996):1168–1174.
6. Marrazzo JM, Ramjee G, Richardson BA, et al. Tenofovir-based preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2015 Feb 5;372(6):509–518.
7. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587–2599.
8. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012 Aug 2;367(5):399–410. doi:10.1056/NEJMoa1108524.
9. Van Damme L, Corneli A, Ahmed K, et al. Preexposure prophylaxis for HIV infection among African women. N Engl J Med. 2012 Aug 2;367(5):411–422.
10. Pitisuttithum P, Gilbert P, Gurwith M, et al. 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. 2006 Dec 15;194(12):1661–1671.
11. Flynn NM, Forthal DN, Harro CD, et al. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005 Mar 1;191(5):654–665.
12. Priddy FH, Brown D, Kublin J, et al. Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults. Clin Infect Dis. 2008 Jun 1;46(11):1769–1781.
13. Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step study):a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008 29;372(9653):1881-1893. doi:10.1016/S0140-6736(08)61591-3.
14. Gray GE, Allen M, Moodie Z, et al. 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. 2011 Jul;11(7):507–515.
15. Duerr A, Huang Y, Buchbinder S, et al. 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. 2012 Jul 15;206(2):258–266.
16. Moodie Z, Metch B, Bekker LG, et al. Continued follow-up of Phambili phase 2b randomized HIV-1 vaccine trial participants supports increased HIV-1 acquisition among vaccinated men. Plos One. 2015;10(9):e0137666.
17. Frahm N, DeCamp AC, Friedrich DP, et al. Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine. J Clin Invest. 2012 Jan 3;122(1):359–367.
18. Janes H, Friedrich DP, Krambrink A, et al. Vaccine-induced gag-specific T cells are associated with reduced viremia after HIV-1 infection. J Infect Dis. 2013 Oct 15;208(8):1231–1239.
19. Leitman EM, Hurst J, Mori M, et al. Lower viral loads and slower CD4+ T-cell count decline in MRKAd5 HIV-1 vaccinees expressing disease-susceptible HLA-B*58:02. J Infect Dis. 2016 Aug 1;214(3):379–389.
20. Hammer SM, Sobieszczyk ME, Janes H, et al. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N Engl J Med. 2013 Nov 28;369(22):2083–2092.• The DNA/rAd5 vaccine regimen did not reduce either the rate of HIV-1 acquisition or the viral-load set point in the population studied. The data support increased risk of HIV-1 infection by MRKAd5 over all follow-up time, but do not support increased risk of HIV-1 infection by DNA/rAd5.
21. Huang Y, Follmann D, Nason M, et al. Effect of rAd5-vector HIV-1 preventive vaccines on HIV-1 acquisition:a participant-level meta-analysis of randomized trials. Plos One. 2015;10(9):e0136626.
22. Belshe RB, Gorse GJ, Mulligan MJ, et al. Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS vaccine evaluation group. AIDS. 1998 Dec 24;12(18):2407–2415.
23. Burton DR, Desrosiers RC, Doms RW, et al. Public health.A sound rationale needed for phase III HIV-1 vaccine trials. Science. 2004 Jan 16;303(5656):316.
24. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009 Dec 3;361(23):2209–2220.• ALVAC-HIV and AIDSVAX B/E vaccine regimen reduces the risk of HIV infection in a community-based population with largely heterosexual risk.
25. Goepfert PA, Elizaga ML, Seaton K, et al. Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis. 2014 Jul 1;210(1):99–110.
26. Robb ML, Rerks-Ngarm S, Nitayaphan S, et al. 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. 2012 Jul;12(7):531–537.
27. Haynes BF, Gilbert PB, McElrath MJ, et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012 Apr 5;366(14):1275–1286.•• This immune-correlates study generated the hypotheses that V1V2 antibodies may have contributed to protection against HIV-1 infection, whereas high levels of Env-specific IgA antibodies may have mitigated the effects of protective antibodies.
28. Lin L, Finak G, Ushey K, et al. COMPASS identifies T-cell subsets correlated with clinical outcomes. Nat Biotechnol. 2015 Jun;33(6):610–616.•• COMPASS improves characterization of antigen-specific T cells and reveals cellular correlates of protection/immunity in the RV144 HIV vaccine efficacy trial.
29. Gray GE, Andersen-Nissen E, Grunenberg N, et al. HVTN 097:evaluation of the RV144 Vaccine Regimen in HIV Uninfected South African Adults. HIVR4P. Cape Town, South Africa:AIDS Research and Human Retroviruses; 2014. p. A33–4.
30. Barouch DH, Alter G, Broge T, et al. Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys. Science. 2015 Jul 17;349(6245):320–324.•• Robust protection by Ad/Env vaccines against acquisition of neutralization-resistant virus challenges in rhesus monkeys.
31. AVAC, HVTN, Janssen. AIDS Vaccine Research:An overview. 2015 [cited; Available from:http://www.avac.org/sites/default/files/event_files/HVAD2015_slides.pdf
32. Gautam R, Nishimura Y, Pegu A, et al. A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. Nature. 2016 May 5;533(7601):105–109.
33. Klein K, Veazey RS, Warrier R, et al. Neutralizing IgG at the portal of infection mediates protection against vaginal simian/human immunodeficiency virus challenge. J Virol. 2013 Nov;87(21):11604–11616.
34. Moldt B, Le KM, Carnathan DG, et al. Neutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques. AIDS. 2016 Jun 19;30(10):1543–1551.
35. Balazs AB, Ouyang Y, Hong CM, et al. Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission. Nat Med. 2014 Mar;20(3):296–300.
36. Binley J, Lybarger E, Crooks E, et al. Profiling the specificity of neutralizing antibodies in a large panel of plasmas from patients chronically infected with human immunodeficiency virus type 1 subtypes B and C. J Virol. 2008 Dec;82(23):11651–11668.
37. Doria-Rose N, Klein R, Daniels M, et al. Breadth of human immunodeficiency virus-specific neutralizing activity in sera:clustering analysis and association with clinical variables. J Virol. 2010 Feb;84(3):1631–1636.
38. Nandi A, Lavine C, Wang P, et al. Epitopes for broad and potent neutralizing antibody responses during chronic infection with human immunodeficiency virus type 1. Virology. 2010 Jan;396(2):339–348.
39. Sather D, Armann J, Ching L, et al. Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J Virol. 2009 Jan;83(2):757–769.
40. Simek M, Rida W, Priddy F, et al. Human immunodeficiency virus type 1 elite neutralizers:individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol. 2009 Jul;83(14):7337–7348.
41. Van Gils M, Euler Z, Schweighardt B, et al. Prevalence of cross-reactive HIV-1-neutralizing activity in HIV-1-infected patients with rapid or slow disease progression. AIDS. 2009 Nov;23(18):2405–2414.
42. Mikell I, Sather DN, Kalams SA, et al. Characteristics of the earliest cross-neutralizing antibody response to HIV-1. Plos Pathog. 2011;7(1):e1001251.
43. Hraber P, Seaman MS, Bailer RT, et al. Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS. 2014 Jan 14;28(2):163–169.
44. Mascola JR, Haynes BF., HIV-1 neutralizing antibodies:understanding nature’s pathways. Immunol Rev. 2013 Jul;254(1):225–244.
45. Sun M, Li Y, Yuan Z, et al. VRC01 antibody protects against vaginal and rectal transmission of human immunodeficiency virus 1 in hu-BLT mice. Arch Virol. 2016 Sep;161(9):2449–2455. doi:10.1007/s00705-016-2942-4.
46. Baba TW, Liska V, Hofmann-Lehmann R, et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat Med. 2000 Feb;6(2):200–206.
47. Burton DR, Hessell AJ, Keele BF, et al. 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 U S A. 2011 Jul;108(27):11181–11186.
48. Hessell AJ, Rakasz EG, Poignard P, et al. Broadly neutralizing human anti-HIV antibody 2G12 is effective in protection against mucosal SHIV challenge even at low serum neutralizing titers. Plos Pathog. 2009 May;5(5):e1000433.
49. Hessell AJ, Rakasz EG, Tehrani DM, et al. Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol. 2010 Feb;84(3):1302–1313.
50. Marx PA, Compans RW, Gettie A, et al. Protection against vaginal SIV transmission with microencapsulated vaccine. Science. 1993;260:1323–1327.
51. Mascola JR, Lewis MG, Stiegler G, et al. Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J Virol. 1999 May;73(5):4009–4018.
52. Moldt B, Rakasz EG, Schultz N, et al. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):18921–18925.
53. Parren PW, Marx PA, Hessell AJ, et al. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J Virol. 2001 Sep;75(17):8340–8347.
54. Barouch DH, Whitney JB, Moldt B, et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature. 2013 Nov 14;503(7475):224–228.
55. Sadjadpour R, Donau OK, Shingai M, et al. Emergence of gp120 V3 variants confers neutralization resistance in an R5 simian-human immunodeficiency virus-infected macaque elite neutralizer that targets the N332 glycan of the human immunodeficiency virus type 1 envelope glycoprotein. J Virol. 2013 Aug;87(15):8798–8804.
56. Scheid JF, Horwitz JA, Bar-On Y, et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016 Jul 28;535(7613):556–560.
57. Trkola A, Kuster H, Rusert P, et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med. 2005 Jun;11(6):615–622.
58. Manrique A, Rusert P, Joos B, et al. In vivo and in vitro escape from neutralizing antibodies 2G12, 2F5, and 4E10. J Virol. 2007 Aug;81(16):8793–8808.
59. Xiao X, Chen W, Feng Y, et al. Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins:implications for evasion of immune responses and design of vaccine immunogens. Biochem Biophys Res Commun. 2009 Dec 18;390(3):404–409.•• This study described the lack of detectable binding of germline-reverted bnAb B cell receptors to recombinant Env proteins and postulated the implications for HIV vaccine design. These results have been subsequently recapitulated by many groups and a number of groups set out to design HIV Env immunogens specifically able to bind germline bnAb BCRs as a result.
60. Hoot S, McGuire AT, Cohen KW, et al. Recombinant HIV envelope proteins fail to engage germline versions of anti-CD4bs bNAbs. Plos Pathog. 2013 Jan;9(1):e1003106.
61. McGuire AT, Hoot S, Dreyer AM, et al. Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies. J Exp Med. 2013 Apr 8;210(4):655–663.•• The first paper demonstrating activation of the VRC01 germline-reverted bnAb BCR and related bnAb BCRs with a modified recombinant HIV Env protein, 426c mutant.
62. Zhou T, Lynch RM, Chen L, et al. Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors. Cell. 2015 Jun 04;161(6):1280–1292.
63. Joyce MG, Zhang B, Ou L, et al. Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat Struct Mol Biol. 2016 Sep;23(9):811–820.
64. McLellan JS, Chen M, Joyce MG, et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science. 2013 Nov 01;342(6158):592–598.
65. Van Regenmortel MH. Structure-based reverse vaccinology failed in the case of HIV because it disregarded accepted immunological theory. Int J Mol Sci. 2016 Sep 21;17(9). pii:E1591.
66. McGuire AT, Dreyer AM, Carbonetti S, et al. HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies. Science. 2014 Dec 12;346(6215):1380–1383.
67. Jardine J, Julien JP, Menis S, et al. Rational HIV immunogen design to target specific germline B cell receptors. Science. 2013 May 10;340(6133):711–716.• One of the first papers demonstrating activation of the VRC01 germline-reverted bnAb BCR with a modified recombinant HIV Env-based multimeric immunogen, eOD-GT6.
68. Georgiev IS, Gordon Joyce M, Zhou T, et al. Elicitation of HIV-1-neutralizing antibodies against the CD4-binding site. Curr Opin HIV AIDS. 2013 Sep;8(5):382–392.
69. McGuire AT, Gray MD, Dosenovic P, et al. Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice. Nat Commun. 2016;7:10618.
70. Jardine JG, Ota T, Sok D, et al. HIV-1 VACCINES. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science. 2015 Jul 10;349(6244):156–161.
71. Dosenovic P, Von Boehmer L, Escolano A, et al. Immunization for HIV-1 broadly neutralizing antibodies in human Ig Knockin mice. Cell. 2015 Jun 18;161(7):1505–1515.• Humanized mice expressing the VRC01-family 3BNC60 bnAb germline-reverted BCR were immunized with germline-targeting immunogens. While the immunogens were able to engage and activate the germline-bnAb lineages, the mice did not develop neutralizing antibodies. The conclusion was that the germline-targeting immunogen was insufficient for inducing neutralization and supported the hypothesis that multiple immunogens would be necessary to drive bnAb development.
72. Briney B, Sok D, Jardine JG, et al. Tailored immunogens direct affinitymaturation toward HIV neutralizing antibodies. Cell. 2016 Sep 8;166(6):1459–70 e11.•• Using a previously described transgenic mouse model expressing the germline-reverted VH of the VRC01 BCR, mice were immunized with eOD-GT8 nanoparticles, followed by intermediate BG505 mutants. Cross-reactive neutralizing antibodies were detected in many of the mice.
73. Tian M, Cheng C, Chen X, et al. Induction of HIV neutralizing antibody lineages in mice with diverse precursor repertoires. Cell. 2016 Sep 8;166(6):1471–84e18.•• This transgenic humanized mouse model was engineered to express the human VH allele commonly found in the VRC01-family of bnAbs, VH1-2• 02 allele. This allowed the mice to have a diverse repertoire of naturally occurring CDR3 recombinations and pairings with endogenous light chains. These mice were then immunized repeatedly with either BG505 WT SOSIP or eOD-GT8 followed by 426c variants and finally the 426c WT SOSIP. Some neutralizing activity was only detected in mice that received the sequential immunizations.
74. Escolano A, Steichen JM, Dosenovic P, et al. Sequential immunization elicits broadly neutralizing anti-HIV-1 antibodies in Ig Knockin mice. Cell. 2016 Sep 8;166(6):1445–58e12.•• Transgenic humanized mice were engineered to express the whole heavy and light chains germline PGT121 BCR. The germline PGT121 mice were immunized with a specifically-designed BG505 Env mutated to increase binding to the germline PGT121 BCR. The mice were vaccinated with subsequent variants, which progressively added back glycans that had been removed from the initial immunogen. The sequential immunization regimen succeeded in inducing potent cross-reactive neutralizing antibodies in multiple mice.
75. Sok D, Briney B, Jardine JG, et al. Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice. Science. 2016 Sep 30;353(6307):1557–1560.
76. Liao HX, Lynch R, Zhou T, et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013 Apr 25;496(7446):469–476.• Longitudinal studies in an HIV-infected individual who develops broad neutralizing serum activity. Paired analysis of longitudinal B cell receptor and viral Env sequence data provides a thorough understanding of the evolution and selective pressures both on the viral and host sides.
77. Gao F, Bonsignori M, Liao HX, et al. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell. 2014 Jul 31;158(3):481–491.
78. Haynes BF, Moody MA, Alam M, et al. Progress in HIV-1 vaccine development. J Allergy Clin Immunol. 2014 Jul;134(1):3–10. quiz 1.
79. Sanders RW, Vesanen M, Schuelke N, et al. Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol. 2002 Sep;76(17):8875–8889.
80. Sanders RW, Derking R, Cupo A, et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. Plos Pathog. 2013 Sep;9(9):e1003618.
81. Julien JP, Sok D, Khayat R, et al. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. Plos Pathog. 2013;9(5):e1003342.
82. Yasmeen A, Ringe R, Derking R, et al. Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Retrovirology. 2014;11:41.
83. Sanders RW, Van Gils MJ, Derking R, et al. HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science. 2015 Jul 10;349(6244):aac4223.•• Immunization in mice demonstrates that the BG505 SOSIP trimer is superior than cleaved recombinant Env trimers in eliciting neutralizing antibodies, although only autologous tier 2 neutralizing antibodies were induced.
84. Hessell AJ, McBurney S, Pandey S, et al. Induction of neutralizing antibodies in rhesus macaques using V3 mimotope peptides. Vaccine. 2016 May 23;34(24):2713–2721.
85. Sharma SK, De Val N, Bale S, et al. Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. Cell Reports. 2015 Apr 28;11(4):539–550.
86. Georgiev IS, Joyce MG, Yang Y, et al. Single-chain soluble BG505.SOSIP gp140 trimers as structural and antigenic mimics of mature closed HIV-1 Env. J Virol. 2015 May;89(10):5318–5329.
87. De Taeye SW, Ozorowski G, De La Pena A, et al. Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposure of non-neutralizing epitopes. Cell. 2015 Dec 17;163(7):1702–1715.
88. Andrabi R, Voss JE, Liang CH, et al. Identification of common features in prototype broadly neutralizing antibodies to HIV envelope V2 apex to facilitate vaccine design. Immunity. 2015 Nov 17;43(5):959–973.
89. Hansen SG, Ford JC, Lewis MS, et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature. 2011 May 26;473(7348):523–527.•• SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge.
90. Hansen SG, Piatak M, Jr., Ventura AB, et al. Immune clearance of highly pathogenic SIV infection. Nature. 2013 Oct 3;502(7469):100–104.
91. Hansen SG, Sacha JB, Hughes CM, et al. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science. 2013 May 24;340(6135):1237874.
92. Hansen SG, Wu HL, Burwitz BJ, et al. Broadly targeted CD8(+) T cell responses restricted by major histocompatibility complex E. Science. 2016 Feb 12;351(6274):714–720.
93. Rolland M, Nickle DC, Mullins JI. HIV-1 group M conserved elements vaccine. Plos Pathog. 2007 Nov;3(11):e157.
94. Fischer W, Perkins S, Theiler J, et al. Polyvalent vaccines for optimal coverage of potential T-cell epitopes in global HIV-1 variants. Nat Med. 2007 Jan;13(1):100–106.
95. Barouch DH, O’Brien KL, Simmons NL, et al. Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med. 2010 Mar;16(3):319–323.
96. Santra S, Liao HX, Zhang R, et al. Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys. Nat Med. 2010 Mar;16(3):324–328.
97. Mothe B, Llano A, Ibarrondo J, et al. CTL responses of high functional avidity and broad variant cross-reactivity are associated with HIV control. Plos One. 2012;7(1):e29717.
98. Kulkarni V, Valentin A, Rosati M, et al. Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques. Plos One. 2014 Jan 23;9(1):e86254.
99. Kulkarni V, Valentin A, Rosati M, et al. HIV-1 conserved elements p24CE DNA vaccine induces humoral immune responses with broad epitope recognition in macaques. Plos One. 2014;9(10):e111085.
100. Chung AW, Kumar MP, Arnold KB, et al. Dissecting polyclonal vaccine-induced humoral immunity against HIV using systems serology. Cell. 2015 Nov 5;163(4):988–998.•• Multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines.
101. Yates NL, Liao HX, Fong Y, et al. Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci Transl Med. 2014 Mar 19;6(228):228ra39.