IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell responses and breadth of humoral immune responses in SIV DNA vaccinated macaques

Human Vaccines and Immunotherapeutics

Volumn 8, Issue 11, 2012, Pages 1620-1629

  Jalah, Rashmi ^a   Patel, Vainav ^a   Kulkarni, Viraj ^a   Rosati, Margherita ^a   Alicea, Candido ^a   Ganneru, Brunda ^a   Von Gegerfelt, Agneta ^a   Huang, Wensheng ^b   Guan, Yongjun ^b   Broderick, Kate E ^c   Sardesai, Niranjan Y ^c   LaBranche, Celia ^d   Montefiori, David C ^d   Pavlakis, George N ^a   Felber, Barbara K ^a  

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

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^c Inovio Pharmaceuticals Inc   (United States)

^d DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Antibody; Avidity; Central memory; Effector memory; HIV; In vivo electroporation; Neutralizing antibody; SIVmac239; SIVsmE660; Transitional memory

Indexed keywords

DNA VACCINE; ENVELOPE PROTEIN; GAG PROTEIN; GAMMA INTERFERON; INTERLEUKIN 12; PLASMID DNA; SIMIAN IMMUNODEFICIENCY VIRUS VACCINE;

ANIMAL EXPERIMENT; ANTIBODY TITER; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOTOXIC T LYMPHOCYTE; ELECTROPORATION; HUMORAL IMMUNITY; MEMORY T LYMPHOCYTE; NONHUMAN; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; PROTEIN FUNCTION; RHESUS MONKEY; VACCINATION;

ANTIBODY; AVIDITY; CENTRAL MEMORY; EFFECTOR MEMORY; HIV; IN VIVO ELECTROPORATION; NEUTRALIZING ANTIBODY; SIVMAC239; SIVSME660; TRANSITIONAL MEMORY;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ELECTROPORATION; IMMUNITY, HUMORAL; INTERLEUKIN-12; MACACA; MACACA MULATTA; SAIDS VACCINES; SIMIAN IMMUNODEFICIENCY VIRUS; T-LYMPHOCYTES, CYTOTOXIC; VACCINES, DNA;

EID: 84869763992     PISSN: 21645515     EISSN: 2164554X     Source Type: Journal    
DOI: 10.4161/hv.21407     Document Type: Article

References (66)

1. Hutnick NA, Myles DJ, Bian CB, Muthumani K, Weiner DB. Selected approaches for increasing HIV DNA vaccine immunogenicity in vivo. Curr Opin Virol 2011; 1:233-40; PMID:22440782; http://dx.doi.org/10.1016/j.coviro.2011.08. 003.
2. Schneider R, Campbell M, Nasioulas G, Felber BK, Pavlakis GN. Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows Rev-independent expression of Gag and Gag/protease and particle formation. J Virol 1997; 71:4892-903; PMID:9188551.
3. Schwartz S, Campbell M, Nasioulas G, Harrison J, Felber BK, Pavlakis GN. Mutational inactivation of an inhibitory sequence in human immunodeficiency virus type 1 results in Rev-independent gag expression. J Virol 1992; 66:7176-82; PMID:1433510.
4. Schwartz S, Felber BK, Pavlakis GN. Distinct RNA sequences in the gag region of human immunodeficiency virus type 1 decrease RNA stability and inhibit expression in the absence of Rev protein. J Virol 1992; 66:150-9; PMID:1727477.
5. Graf M, Deml L, Wagner R. Codon-optimized genes that enable increased heterologous expression in mammalian cells and elicit efficient immune responses in mice after vaccination of naked DNA. Methods Mol Med 2004; 94:197-210; PMID:14959831.
6. Deml L, Bojak A, Steck S, Graf M, Wild J, Schirmbeck R, et al. Multiple effects of codon usage optimization on expression and immunogenicity of DNA candidate vaccines encoding the human immunodeficiency virus type 1 Gag protein. J Virol 2001; 75:10991-1001; PMID:11602739; http://dx.doi.org/10.1128/JVI.75. 22.10991-11001.2001.
7. Nasioulas G, Zolotukhin AS, Tabernero C, Solomin L, Cunningham CP, Pavlakis GN, et al. Elements distinct from human immunodeficiency virus type 1 splice sites are responsible for the Rev dependence of env mRNA. J Virol 1994; 68:2986-93; PMID:8151769.
8. Kulkarni V, Jalah R, Ganneru B, Bergamaschi C, Alicea C, von Gegerfelt A, et al. Comparison of immune responses generated by optimized DNA vaccination against SIV antigens in mice and macaques. Vaccine 2011; 29:6742-54; PMID:21195080; http://dx.doi.org/10.1016/j.vaccine.2010.12.056.
9. de Arruda LB, Chikhlikar PR, August JT, Marques ET. DNA vaccine encoding human immunodeficiency virus-1 Gag, targeted to the major histocompatibility complex II compartment by lysosomal-associated membrane protein, elicits enhanced long-term memory response. Immunology 2004; 112:126-33; PMID:15129672; http://dx.doi.org/10.1111/j.1365-2567.2004.01823.x.
10. Marques ET Jr., Chikhlikar P, de Arruda LB, Leao IC, Lu Y, Wong J, et al. HIV-1 p55Gag encoded in the lysosome-associated membrane protein-1 as a DNA plasmid vaccine chimera is highly expressed, traffics to the major histocompatibility class II compartment, and elicits enhanced immune responses. J Biol Chem 2003; 278:37926-36; PMID:12824194; http://dx.doi.org/10.1074/jbc. M303336200.
11. Valentin A, Chikhlikar P, Patel V, Rosati M, Maciel M, Chang KH, et al. Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes. Vaccine 2009; 27:4840-9; PMID:19539586; http://dx.doi.org/10.1016/j.vaccine. 2009.05.093.
12. Biragyn A, Belyakov IM, Chow YH, Dimitrov DS, Berzofsky JA, Kwak LW. DNA vaccines encoding human immunodeficiency virus-1 glycoprotein 120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses. Blood 2002; 100:1153-9; PMID:12149191; http://dx.doi.org/10.1182/blood-2002-01- 0086.
13. Rosati M, von Gegerfelt A, Roth P, Alicea C, Valentin A, Robert-Guroff M, et al. DNA vaccines expressing different forms of simian immunodeficiency virus antigens decrease viremia upon SIVmac251 challenge. J Virol 2005; 79:8480-92; PMID:15956591; http://dx.doi.org/10.1128/JVI.79.13.8480-8492.2005.
14. Sardesai NY, Weiner DB. Electroporation delivery of DNA vaccines: prospects for success. Curr Opin Immunol 2011; 23:421-9; PMID:21530212; http://dx.doi.org/10.1016/j.coi.2011.03.008.
15. Patel V, Valentin A, Kulkarni V, Rosati M, Bergamaschi C, Jalah R, et al. Long-lasting humoral and cellular immune responses and mucosal dissemination after intramuscular DNA immunization. Vaccine 2010; 28:4827-36; PMID:20451642; http://dx.doi.org/10.1016/j.vaccine.2010.04.064.
16. Rosati M, Bergamaschi C, Valentin A, Kulkarni V, Jalah R, Alicea C, et al. DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge. Proc Natl Acad Sci U S A 2009; 106:15831-6; PMID:19717425; http://dx.doi.org/10.1073/pnas. 0902628106.
17. Rosati M, Valentin A, Jalah R, Patel V, von Gegerfelt A, Bergamaschi C, et al. Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation. Vaccine 2008; 26:5223-9; PMID:18468743; http://dx.doi.org/10.1016/j.vaccine.2008.03.090.
18. Winstone N, Wilson AJ, Morrow G, Boggiano C, Chiuchiolo MJ, Lopez M, et al. Enhanced control of pathogenic SIVmac239 replication in macaques immunized with a plasmid IL12 and a DNA prime, viral vector boost vaccine regimen. J Virol 2011; 85:9578-87; PMID:21734035; http://dx.doi.org/10.1128/JVI.05060-11.
19. Luckay A, Sidhu MK, Kjeken R, Megati S, Chong SY, Roopchand V, et al. Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J Virol 2007; 81:5257-69; PMID:17329330; http://dx.doi.org/10.1128/JVI.00055-07.
20. Hirao LA, Wu L, Khan AS, Hokey DA, Yan J, Dai A, et al. Combined effects of IL-12 and electroporation enhances the potency of DNA vaccination in macaques. Vaccine 2008; 26:3112-20; PMID:18430495; http://dx.doi.org/10.1016/j. vaccine.2008.02.036.
21. Vojnov L, Bean AT, Peterson EJ, Chiuchiolo MJ, Sacha JB, Denes FS, et al. DNA/Ad5 vaccination with SIV epitopes induced epitope-specific CD4+ T cells, but few subdominant epitope-specific CD8+ T cells. Vaccine 2011; 29:7483-90; PMID:21839132; http://dx.doi.org/10.1016/j.vaccine.2011.07.048.
22. Vasan S, Hurley A, Schlesinger SJ, Hannaman D, Gardiner DF, Dugin DP, et al. In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS One 2011; 6:e19252; PMID:21603651; http://dx.doi.org/10.1371/journal.pone.0019252.
23. Vasan S, Schlesinger SJ, Huang Y, Hurley A, Lombardo A, Chen Z, et al. Phase 1 safety and immunogenicity evaluation of ADVAX, a multigenic, DNAbased clade C/B' HIV-1 candidate vaccine. PLoS One 2010; 5:e8617; PMID:20111582; http://dx.doi.org/10.1371/journal.pone.0008617.
24. Boyer JD, Robinson TM, Kutzler MA, Vansant G, Hokey DA, Kumar S, et al. Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid. Proc Natl Acad Sci U S A 2007; 104:18648-53; PMID:18000037; http://dx.doi.org/10.1073/pnas.0709198104.
25. Muthumani K, Bagarazzi M, Conway D, Hwang DS, Manson K, Ciccarelli R, et al. A Gag-Pol/Env-Rev SIV239 DNA vaccine improves CD4 counts, and reduce viral loads after pathogenic intrarectal SIV(mac)251 challenge in rhesus Macaques. Vaccine 2003; 21:629-37; PMID:12531331; http://dx.doi.org/10.1016/S0264-410X(02) 00571-6.
26. Boyer JD, Maciag PC, Parkinson R, Wu L, Lewis MG, Weiner DB, et al. Rhesus macaques with high levels of vaccine induced IFN-gamma producing cells better control viral set-point following challenge with SIV239. Vaccine 2006; 24:4498-502; PMID:16185790; http://dx.doi.org/10.1016/j.vaccine.2005.08.016.
27. Boyer JD, Cohen AD, Ugen KE, Edgeworth RL, Bennett M, Shah A, et al. Therapeutic immunization of HIV-infected chimpanzees using HIV-1 plasmid antigens and interleukin-12 expressing plasmids. AIDS 2000; 14:1515-22; PMID:10983638; http://dx.doi.org/10.1097/00002030-200007280-00007.
28. Boyer JD, Robinson TM, Kutzler MA, Parkinson R, Calarota SA, Sidhu MK, et al. SIV DNA vaccine coadministered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques. J Med Primatol 2005; 34:262-70; PMID:16128921; http://dx.doi.org/10.1111/j.1600-0684.2005.00124.x.
29. Chattergoon MA, Saulino V, Shames JP, Stein J, Montaner LJ, Weiner DB. Co-immunization with plasmid IL-12 generates a strong T-cell memory response in mice. Vaccine 2004; 22:1744-50; PMID:15068858; http://dx.doi.org/10.1016/j. vaccine.2004.01.036.
30. Chong SY, Egan MA, Kutzler MA, Megati S, Masood A, Roopchard V, et al. Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV(89.6P) challenge in rhesus macaques. Vaccine 2007; 25:4967-82; PMID:17335943; http://dx.doi.org/10.1016/j.vaccine.2006.11.070.
31. Egan MA, Chong SY, Megati S, Montefiori DC, Rose NF, Boyer JD, et al. Priming with plasmid DNAs expressing interleukin-12 and simian immunodeficiency virus gag enhances the immunogenicity and efficacy of an experimental AIDS vaccine based on recombinant vesicular stomatitis virus. AIDS Res Hum Retroviruses 2005; 21:629-43; PMID:16060834; http://dx.doi.org/10.1089/aid.2005. 21.629.
32. Egan MA, Megati S, Roopchand V, Garcia-Hand D, Luckay A, Chong SY, et al. Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice. Vaccine 2006; 24:4510-23; PMID:16140439; http://dx.doi.org/10.1016/j.vaccine.2005.08.024.
33. Halwani R, Boyer JD, Yassine-Diab B, Haddad EK, Robinson TM, Kumar S, et al. Therapeutic vaccination with simian immunodeficiency virus (SIV)-DNA + IL-12 or IL-15 induces distinct CD8 memory subsets in SIV-infected macaques. J Immunol 2008; 180:7969-79; PMID:18523260.
34. Kim JJ, Ayyavoo V, Bagarazzi ML, Chattergoon MA, Dang K, Wang B, et al. In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen. J Immunol 1997; 158:816-26; PMID:8992999.
35. Kim JJ, Nottingham LK, Tsai A, Lee DJ, Maguire HC, Oh J, et al. Antigen-specific humoral and cellular immune responses can be modulated in rhesus macaques through the use of IFN-gamma, IL-12, or IL-18 gene adjuvants. J Med Primatol 1999; 28:214-23; PMID:10593488; http://dx.doi.org/10.1111/j.1600- 0684.1999.tb00272.x.
36. Kim JJ, Simbiri KA, Sin JI, Dang K, Oh J, Dentchev T, et al. Cytokine molecular adjuvants modulate immune responses induced by DNA vaccine constructs for HIV-1 and SIV. J Interferon Cytokine Res 1999; 19:77-84; PMID:10048771; http://dx.doi.org/10.1089/107999099314441.
37. Kim JJ, Trivedi NN, Nottingham LK, Morrison L, Tsai A, Hu Y, et al. Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. Eur J Immunol 1998; 28:1089-103; PMID:9541605; http://dx.doi.org/10.1002/(SICI) 1521-4141(199803)28:03〈1089::AIDIMMU1089〉3.0.CO;2-L.
38. Morrow MP, Yan J, Pankhong P, Ferraro B, Lewis MG, Khan AS, et al. Unique Th1/Th2 phenotypes induced during priming and memory phases by use of interleukin-12 (IL-12) or IL-28B vaccine adjuvants in rhesus macaques. Clin Vaccine Immunol 2010; 17:1493-9; PMID:20685940; http://dx.doi.org/10.1128/CVI. 00181-10.
39. Robinson TM, Sidhu MK, Pavlakis GN, Felber BK, Silvera P, Lewis MG, et al. Macaques co-immunized with SIVgag/pol-HIVenv and IL-12 plasmid have increased cellular responses. J Med Primatol 2007; 36:276-84; PMID:17669216; http://dx.doi.org/10.1111/j.1600-0684.2007.00245.x.
40. Schadeck EB, Sidhu M, Egan MA, Chong S-Y, Piacente P, Masood A, et al. Plasmid encoded IL-12 functions as a DNA vaccine adjuvant and augments SIVgag-specific cell-mediated and humoral immune responses in Rhesus macaques. Vaccine 2006; 24:4677-87; PMID:16288822; http://dx.doi.org/10.1016/j.vaccine. 2005.10.035.
41. Schadeck EB, Sidhu M, Egan MA, Chong SY, Piacente P, Masood A, et al. A dose sparing effect by plasmid encoded IL-12 adjuvant on a SIVgag-plasmid DNA vaccine in rhesus macaques. Vaccine 2006; 24:4677-87; PMID:16288822; http://dx.doi.org/10.1016/j.vaccine.2005.10.035.
42. Xu R, Megati S, Roopchand V, Luckay A, Masood A, Garcia-Hand D, et al. Comparative ability of various plasmid-based cytokines and chemokines to adjuvant the activity of HIV plasmid DNA vaccines. Vaccine 2008; 26:4819-29; PMID:18657584; http://dx.doi.org/10.1016/j.vaccine.2008.06.103.
43. O'Neill E, Bostik V, Montefiori DC, Kraiselburd E, Villinger F. IL-12/GM-CSF coadministration in an SIV DNA prime/protein boost protocol enhances Gag-specific T cells but not virus-specific neutralizing antibodies in rhesus macaques. AIDS Res Hum Retroviruses 2003; 19:883-90; PMID:14585220; http://dx.doi.org/10.1089/088922203322493058.
44. Kalams SA, Parker S, Jin X, Elizaga M, Metch B, Wang M, et al.; NIAID HIV Vaccine Trials Network. Safety and immunogenicity of an HIV-1 gag DNA vaccine with or without IL-12 and/or IL-15 plasmid cytokine adjuvant in healthy, HIV-1 uninfected adults. PLoS One 2012; 7:e29231; PMID:22242162; http://dx.doi.org/10. 1371/journal.pone.0029231.
45. Manetti R, Gerosa F, Giudizi MG, Biagiotti R, Parronchi P, Piccinni MP, et al. Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones. J Exp Med 1994; 179:1273-83; PMID:7908322; http://dx.doi.org/10.1084/jem.179.4.1273.
46. Meyaard L, Hovenkamp E, Otto SA, Miedema F. IL-12-induced IL-10 production by human T cells as a negative feedback for IL-12-induced immune responses. J Immunol 1996; 156:2776-82; PMID:8609396.
47. Leonard JP, Sherman ML, Fisher GL, Buchanan LJ, Larsen G, Atkins MB, et al. Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production. Blood 1997; 90:2541-8; PMID:9326219.
48. Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess DC, Drummond DD, et al. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat Med 2009; 15:293-9; PMID:19219024; http://dx.doi.org/10.1038/nm.1935.
49. Pitcher CJ, Hagen SI, Walker JM, Lum R, Mitchell BL, Maino VC, et al. Development and homeostasis of T cell memory in rhesus macaque. J Immunol 2002; 168:29-43; PMID:11751943.
50. Gherardi MM, Ramírez JC, Esteban M. Interleukin-12 (IL-12) enhancement of the cellular immune response against human immunodeficiency virus type 1 env antigen in a DNA prime/vaccinia virus boost vaccine regimen is time and dose dependent: suppressive effects of IL-12 boost are mediated by nitric oxide. J Virol 2000; 74:6278-86; PMID:10864637; http://dx.doi.org/10.1128/JVI. 74.14.6278-6286.2000.
51. Lasarte JJ, Corrales FJ, Casares N, López-Díaz de Cerio A, Qian C, Xie X, et al. Different doses of adenoviral vector expressing IL-12 enhance or depress the immune response to a coadministered antigen: the role of nitric oxide. J Immunol 1999; 162:5270-7; PMID:10228002.
52. Lee K, Overwijk WW, O-Toole M, Swiniarski H, Restifo NP, Dorner AJ, et al. Dose-dependent and schedule-dependent effects of interleukin-12 on antigen-specific CD8 responses. J Interferon Cytokine Res 2000; 20:589-96; PMID:10888115; http://dx.doi.org/10.1089/10799900050044787.
53. Chowdhury FZ, Ramos HJ, Davis LS, Forman J, Farrar JD. IL-12 selectively programs effector pathways that are stably expressed in human CD8+ effector memory T cells in vivo. Blood 2011; 118:3890-900; PMID:21832277; http://dx.doi.org/10.1182/blood-2011-05-357111.
54. Killian MS, Johnson C, Teque F, Fujimura S, Levy JA. Natural suppression of human immunodeficiency virus type 1 replication is mediated by transitional memory CD8+ T cells. J Virol 2011; 85:1696-705; PMID:21147929; http://dx.doi.org/10.1128/JVI.01120-10.
55. Picker LJ, Hansen SG, Lifson JD. New paradigms for HIV/AIDS vaccine development. Annu Rev Med 2012; 63:95-111; PMID:21942424; http://dx.doi.org/10. 1146/annurev-med-042010-085643.
56. Frahm MA, Picking RA, Kuruc JD, McGee KS, Gay CL, Eron JJ, et al. CD4+CD8+ T cells represent a significant portion of the anti-HIV T cell response to acute HIV infection. J Immunol 2012; 188:4289-96; PMID:22461689; http://dx.doi.org/10.4049/jimmunol.1103701.
57. Holznagel E, Norley S, Holzammer S, Coulibaly C, Kurth R. Immunological changes in simian immunodeficiency virus (SIV(agm))-infected African green monkeys (AGM): expanded cytotoxic T lymphocyte, natural killer and B cell subsets in the natural host of SIV(agm). J Gen Virol 2002; 83:631-40; PMID:11842258.
58. Howe R, Dillon S, Rogers L, Palmer B, MaWhinney S, Blyveis N, et al. Phenotypic and functional characterization of HIV-1-specific CD4+CD8+ double-positive T cells in early and chronic HIV-1 infection. J Acquir Immune Defic Syndr 2009; 50:444-56; PMID:19360930; http://dx.doi.org/10.1097/QAI. 0b013e31819aa8c4.
59. Nascimbeni M, Pol S, Saunier B. Distinct CD4+ CD8+ double-positive T cells in the blood and liver of patients during chronic hepatitis B and C. PLoS One 2011; 6:e20145; PMID:21647449; http://dx.doi.org/10.1371/journal.pone. 0020145.
60. Nascimbeni M, Shin EC, Chiriboga L, Kleiner DE, Rehermann B. Peripheral CD4(+)CD8(+) T cells are differentiated effector memory cells with antiviral functions. Blood 2004; 104:478-86; PMID:15044252; http://dx.doi.org/10.1182/ blood-2003-12-4395.
61. Valentin A, von Gegerfelt A, Rosati M, Miteloudis G, Alicea C, Bergamaschi C, et al. Repeated DNA therapeutic vaccination of chronically SIV-infected macaques provides additional virological benefit. Vaccine 2010; 28:1962-74; PMID:20188252; http://dx.doi.org/10.1016/j.vaccine.2009.10.099.
62. Guan Y, Sajadi MM, Kamin-Lewis R, Fouts TR, Dimitrov A, Zhang Z, et al. Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infection. Proc Natl Acad Sci U S A 2009; 106:3952-7; PMID:19225108; http://dx.doi.org/10.1073/pnas.0813392106.
63. Moore JP, Wallace LA, Follett EA, McKeating JA. An enzyme-linked immunosorbent assay for antibodies to the envelope glycoproteins of divergent strains of HIV-1. AIDS 1989; 3:155-63; PMID:2540772; http://dx.doi.org/10.1097/ 00002030-198903000-00006.
64. Xiao P, Zhao J, Patterson LJ, Brocca-Cofano E, Venzon D, Kozlowski PA, et al. Multiple vaccine-elicited nonneutralizing antienvelope antibody activities contribute to protective efficacy by reducing both acute and chronic viremia following simian/human immunodeficiency virus SHIV89.6P challenge in rhesus macaques. J Virol 2010; 84:7161-73; PMID:20444898; http://dx.doi.org/10.1128/ JVI.00410-10.
65. Montefiori DC. Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase reporter gene assays. Curr Protoc Immunol 2005; Chapter 12:Unit 12 1.
66. Keele BF, Li H, Learn GH, Hraber P, Giorgi EE, Grayson T, et al. Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med 2009; 206:1117-34; PMID:19414559; http://dx.doi.org/10.1084/jem.20082831.