Challenges in mucosal HIV vaccine development: Lessons from non-human primate models

Viruses

Volumn 6, Issue 8, 2014, Pages 3129-3158

  Tuero, Iskra ^a   Robert Guroff, Marjorie ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

HIV vaccine; Mucosal immunity; Non human primate

Indexed keywords

HUMAN IMMUNODEFICIENCY VIRUS VACCINE; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; TOLL LIKE RECEPTOR;

CELLULAR IMMUNITY; DENDRITIC CELL; DRUG EFFICACY; ENZYME LINKED IMMUNOSORBENT ASSAY; GASTROINTESTINAL TRACT VACCINATION; HUMAN; IMMUNE RESPONSE; MACROPHAGE; MUCOSAL IMMUNITY; MULTICENTER STUDY (TOPIC); NONHUMAN; PHAGOCYTOSIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIMATE MODEL; REVIEW; VACCINATION; VIRUS NEUTRALIZATION; VIRUS TRANSMISSION; ANIMAL; DISEASE MODEL; DRUG DEVELOPMENT; HIV INFECTIONS; IMMUNOLOGY; ISOLATION AND PURIFICATION; MUCOSAL ADMINISTRATION; PRIMATE; PROCEDURES; TRENDS;

ADMINISTRATION, MUCOSAL; AIDS VACCINES; ANIMALS; DISEASE MODELS, ANIMAL; DRUG DISCOVERY; HIV INFECTIONS; HUMANS; PRIMATES;

EID: 84925884708     PISSN: 19994915     EISSN: None     Source Type: Journal    
DOI: 10.3390/v6083129     Document Type: Review

References (149)

1. Haase, A.T. Perils at mucosal front lines for HIV and SIV and their hosts. Nat. Rev. Immunol. 2005, 5, 783-792.
2. Miller, C.J.; Li, Q.; Abel, K.; Kim, E.Y.; Ma, Z.M.; Wietgrefe, S.; La Franco-Scheuch, L.; Compton, L.; Duan, L.; Shore, M.D.; et al. Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J. Virol. 2005, 79, 9217-9227.
3. Ribeiro Dos Santos, P.; Rancez, M.; Prétet, J.L.; Michel-Salzat, A.; Messent, V.; Bogdanova, A.; Couëdel-Courteille, A.; Souil, E.; Cheynier, R.; Butor, C. Rapid dissemination of SIV follows multisite entry after rectal inoculation. PLoS One 2011, 6, e19493.
4. Brenchley, J.M. Mucosal immunity in human and simian immunodeficiency lentivirus infections. Mucosal Immunol. 2013, 6, 657-665.
5. Kraehenbuhl, J.P.; Neutra, M.R. Mucosal vaccines: Where do we stand? Curr. Top. Med. Chem. 2013, 13, 2609-2628.
6. Rancez, M.; Couëdel-Courteille, A.; Cheynier, R. Chemokines at mucosal barriers and their impact on HIV infection. Cytokine Growth Factor Rev. 2012, 23, 233-243.
7. Tengroth, L.; Millrud, C.R.; Kvarnhammar, A.M.; Georén, S.K.; Latif, L.; Cardell, L.O. Functional effects of toll-like receptor (TLR)3, 7, 9, RIG-I and MDA stimulation in nasalepithelial cells. PLoS One 2014, 9, e98239.
8. Cavarelli, M.; Scarlatti, G. HIV-1 Infection: The Role of the Gastrointestinal Tract. Am. J. Reprod. Immunol. 2014, 71, 537-542.
9. Genescà, M.; McChesney, M.B.; Miller, C.J. Antiviral CD8+ T cells in the genital tract control viral replication and delay progression to AIDS after vaginal SIV challenge in rhesus macaques immunized with virulence attenuated SHIV89.6. J. Intern. Med. 2009, 265, 67-77.
10. Manrique, M.; Kozlowski, P.A.; Cobo-Molinos, A.; Wang, S.W.; Wilson, R.L.; Martinez-Viedma, M.P.; Montefiori, D.C.; Carville, A.; Aldovini, A. Resistance to infection, early and persistent suppression of simian immunodeficiency virus SIVmac251 viremia, and significant reduction of tissue viral burden after mucosal vaccination in female rhesus macaques. J. Virol. 2014, 88, 212-224.
11. Corthésy, B. Multi-faceted functions of secretory IgA at mucosal surfaces. Front. Immunol. 2013, 4, 185.
12. Baba, T.W.; Liska, V.; Hofmann-Lehmann, R.; Vlasak, J.; Xu, W.; Ayehunie, S.; Cavacini, L.A.; Posner, M.R.; Katinger, H.; Stiegler, G.; et al. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat. Med. 2000, 6, 200-206.
13. Mascola, J.R.; Stiegler, G.; VanCott, T.C.; Katinger, H.; Carpenter, C.B.; Hanson, C.E.; Beary, H.; Hayes, D.; Frankel, S.S.; Birx, D.L.; et al. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat. Med. 2000, 6, 207-210.
14. Hidajat, R.; Xiao, P.; Zhou, Q.; Venzon, D.; Summers, L.E.; Kalyanaraman, V.S.; Montefiori, D.C.; Robert-Guroff, M. Correlation of vaccine-elicited systemic and mucosal nonneutralizing antibody activities with reduced acute viremia following intrarectal simian immunodeficiency virus SIVmac251 challenge of rhesus macaques. J. Virol. 2009, 83, 791-801.
15. Xiao, P.; Zhao, J.; Patterson, L.J.; Brocca-Cofano, E.; Venzon, D.; Kozlowski, P.A.; Hidajat, R.; Demberg, T.; Robert-Guroff, M. 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, 7161-7173.
16. Xiao, P.; Patterson, L.J.; Kuate, S.; Brocca-Cofano, E.; Thomas, M.A.; Venzon, D.; Zhao, J.; DiPasquale, J.; Fenizia, C.; Lee, E.M.; et al. Replicating adenovirus-simian immunodeficiency virus (SIV) recombinant priming and envelope protein boosting elicits localized, mucosal IgA immunity in rhesus macaques correlated with delayed acquisition following a repeated low-dose rectal SIV(mac251) challenge. J. Virol. 2012, 86, 4644-4657.
17. Bomsel, M.; Tudor, D.; Drillet, A.S.; Alfsen, A.; Ganor, Y.; Roger, M.G.; Mouz, N.; Amacker, M.; Chalifour, A.; Diomede, L.; et al. Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. Immunity 2011, 34, 269-280.
18. Fahrbach, K.M.; Malykhina, O.; Stieh, D.J.; Hope, T.J. Differential binding of IgG and IgA to mucus of the female reproductive tract. PLoS One 2013, 8, e76176.
19. Alexander, R.; Mestecky, J. Neutralizing antibodies in mucosal secretions: IgG or IgA? Curr. HIV Res. 2007, 5, 588-593.
20. Mestecky, J.; Wei, Q.; Alexander, R.; Raska, M.; Novak, J.; Moldoveanu, Z. Humoral Immune Responses to HIV in the Mucosal Secretions and Sera of HIV-Infected Women. Am. J. Reprod. Immunol. 2014, 71, 600-607.
21. Donadoni, C.; Bisighini, C.; Scotti, L.; Diomede, L.; Ngyen, M.; Nouhin, J.; DeSantis, L.; Zambon, A.; Ferrari, D.; Gallotta, G.; et al. Setting of methods for analysis of mucosal antibodies in seminal and vaginal fluids of HIV seropositive subjects from Cambodian and Italian cohorts. PLoS One 2010, 5, e9920.
22. Musich, T.; Demberg, T.; Ian, L.; Estes, J.D.; Franchini, G.; Robert-Guroff, M. Purification and Functional characterization of mucosal IgA from vaccinated and SIV-infected rhesus macaques. HIV Vaccines: Adaptive Immunity and Beyond. Keystone symposium 2014, Banff, Alberta, CA, USA, 2014.
23. Hocini, H.; Bomsel, M. Infectious human immunodeficiency virus can rapidly penetrate a tight human epithelial barrier by transcytosis in a process impaired by mucosal immunoglobulins. J. Infect. Dis. 1999, 179, S448-S453.
24. Devito, C.; Broliden, K.; Kaul, R.; Svensson, L.; Johansen, K.; Kiama, P.; Kimani, J.; Lopalco, L.; Piconi, S.; Bwayo, J.J.; et al. Mucosal and plasma IgA from HIV-1-exposed uninfected individuals inhibit HIV-1 transcytosis across human epithelial cells. J. Immunol. 2000, 165, 5170-5176.
25. Kozlowski, P.A.; Williams, S.B.; Lynch, R.M.; Flanigan, T.P.; Patterson, R.R.; Cu-Uvin, S.; Neutra, M.R. Differential induction of mucosal and systemic antibody responses in women after nasal, rectal, or vaginal immunization: Influence of the menstrual cycle. J. Immunol. 2002, 169, 566-574.
26. Jespers, V.; Harandi, A.M.; Hinkula, J.; Medaglini, D.; Le Grand, R.; Stahl-Hennig, C.; Bogers, W.; El Habib, R.; Wegmann, F.; Fraser, C.; et al. Assessment of mucosal immunity to HIV-1. Expert Rev. Vaccin. 2010, 9, 381-394.
27. Lewis, D.J.; Fraser, C.A.; Mahmoud, A.N.; Wiggins, R.C.; Woodrow, M.; Cope, A.; Cai, C.; Giemza, R.; Jeffs, S.A.; Manoussaka, M.; et al. Phase I randomised clinical trial of an HIV-1(CN54), clade C, trimeric envelope vaccine candidate delivered vaginally. PLoS One 2011, 6, e25165.
28. Gordon, S.N.; Kines, R.C.; Kutsyna, G.; Ma, Z.M.; Hryniewicz, A.; Roberts, J.N.; Fenizia, C.; Hidajat, R.; Brocca-Cofano, E.; Cuburu, N.; et al. Targeting the vaginal mucosa with human papillomavirus pseudovirion vaccines delivering simian immunodeficiency virus DNA. J. Immunol. 2012, 188, 714-723.
29. Powell, R.L.; Ouellette, I.; Lindsay, R.W.; Parks, C.L.; King, C.R.; McDermott, A.B.; Morrow, G. A Multiplex Microsphere-Based Immunoassay Increases the Sensitivity of SIV-Specific Antibody Detection in Serum Samples and Mucosal Specimens Collected from Rhesus Macaques Infected with SIVmac239. Biores. Open Access. 2013, 2, 171-178.
30. Leroux-Roels, G.; Maes, C.; Clement, F.; van Engelenburg, F.; van den Dobbelsteen, M.; Adler, M.; Amacker, M.; Lopalco, L.; Bomsel, M.; Chalifour, A.; et al. Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes. PLoS One 2013, 8, e55438.
31. Mestecky, J.; Alexander, R.C.; Wei, Q.; Moldoveanu, Z. Methods for evaluation of humoral immune responses in human genital tract secretions. Am. J. Reprod. Immunol. 2011, 65, 361-367.
32. Boesch, A.W.; Zhao, Y.; Landman, A.S.; Garcia, M.R.; Fahey, J.V.; Wira, C.R.; Ackerman, M.E. A multiplexed assay to detect antimicrobial peptides in biological fluids and cell secretions. J. Immunol. Methods. 2013, 397, 71-76.
33. Boskey, E.R.; Moench, T.R.; Hees, P.S.; Cone, R.A. A self-sampling method to obtain large volumes of undiluted cervicovaginal secretions. Sex. Transm. Dis. 2003, 30, 107-109.
34. Mesin, L.; Di Niro, R.; Thompson, K.M.; Lundin, K.E.; Sollid, L.M. Long-lived plasma cells from human small intestine biopsies secrete immunoglobulins for many weeks in vitro. J. Immunol. 2011, 187, 2867-2874.
35. Schäfer, F.; Kewenig, S.; Stolte, N.; Stahl-Hennig, C.; Stallmach, A.; Kaup, F.J.; Zeitz, M.; Schneider, T. Lack of simian immunodeficiency virus (SIV) specific IgA response in the intestine of SIV infected rhesus macaques. Gut. 2002, 50, 608-614.
36. Thomas, M.A.; Demberg, T.; Vargas-Inchaustegui, D.A.; Xiao, P.; Tuero, I.; Venzon, D.; Weiss, D.; Treece, J.; Robert-Guroff, M. Rhesus macaque rectal and duodenal tissues exhibit B-cell sub-populations distinct from peripheral blood that continuously secrete antigen-specific IgA in short-term explant cultures. Vaccine 2014, 32, 872-880.
37. Bertley, F.M.; Kozlowski, P.A.; Wang, S.W.; Chappelle, J.; Patel, J.; Sonuyi, O.; Mazzara, G.; Montefiori, D.; Carville, A.; Mansfield, K.G.; et al. Control of simian/human immunodeficiency virus viremia and disease progression after IL-2-augmented DNA modified vaccinia virus Ankara nasal vaccination in nonhuman primates. J. Immunol. 2004, 172, 3745-3757.
38. Manrique, M.; Kozlowski, P.A.; Wang, S.W.; Wilson, R.L.; Micewicz, E.; Montefiori, D.C.; Mansfield, K.G.; Carville, A.; Aldovini, A. Nasal DNA-MVA SIV vaccination provides more significant protection from progression to AIDS than a similar intramuscular vaccination. Mucosal Immunol. 2009, 2, 536-550.
39. Mestecky, J. Humoral immune responses to the human immunodeficiency virus type-1 (HIV-1) in the genital tract compared to other mucosal sites. J. Reprod. Immunol. 2006, 72, 1-17.
40. Hadzic, S.V.; Wang, X.; Dufour, J.; Doyle, L.; Marx, P.A.; Lackner, A.A.; Paulsen, D.B.; Veazey, R.S. Comparison of the Vaginal environment of Macaca mulatta and Macaca nemestrina Throughout the Menstrual Cycle. Am. J. Reprod. Immunol. 2014, 71, 322-329.
41. McNicholl, J.M.; Henning, T.C.; Vishwanathan, S.A.; Kersh, E.N. Non-Human Primate Models of Hormonal Contraception and HIV. Am. J. Reprod. Immunol. 2014, 71, 513-522.
42. Thomas, J.S.; Lacour, N.; Kozlowski, P.A.; Nelson, S.; Bagby, G.J.; Amedee, A.M. Characterization of SIV in the oral cavity and in vitro inhibition of SIV by rhesus macaque saliva. AIDS Res. Hum. Retrovir. 2010, 26, 901-911.
43. Lajoie, J.; Juno, J.; Burgener, A.; Rahman, S.; Mogk, K.; Wachihi, C.; Mwanjewe, J.; Plummer, F.A.; Kimani, J.; Ball, T.B.; et al. A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers. Mucosal Immunol. 2012, 5, 277-287.
44. Lieberman, J.A.; Moscicki, A.B.; Sumerel, J.L.; Ma, Y.; Scott, M.E. Determination of cytokine protein levels in cervical mucus samples from young women by a multiplex immunoassay method and assessment of correlates. Clin. Vaccin. Immunol. 2008, 15, 49-54.
45. Mohanram, V.; Demberg, T.; Tuero, I.; Vargas-Inchaustegui, D.; Pavlakis, G.N.; Felber, B.K.; Robert-Guroff, M. Improved flow-based method for HIV/SIV envelope-specific memory B-cell evaluation in rhesus macaques. J. Immunol. Meth. 2014, in press.
46. Demberg, T.; Mohanram, V.; Venzon, D.; Robert-Guroff, M. Phenotypes and distribution of mucosal memory B cell populations in the SIV/SHIV Rhesus macaque model. Clin. Immunol. 2014, in press.
47. Haynes, B.F.; Gilbert, P.B.; McElrath, M.J.; Zolla-Pazner, S.; Tomaras, G.D.; Alam, S.M.; Evans, D.T.; Montefiori, D.C.; Karnasuta, C.; Sutthent, R.; et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 2012, 366, 1275-1286.
48. Bonsignori, M.; Pollara, J.; Moody, M.A.; Alpert, M.D.; Chen, X.; Hwang, K.K.; Gilbert, P.B.; Huang, Y.; Gurley, T.C.; Kozink, D.M.; et al. 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. 2012, 86, 11521-11532.
49. Benmira, S.; Bhattacharya, V.; Schmid, M.L. An effective HIV vaccine: A combination of humoral and cellular immunity? Curr. HIV Res. 2010, 8, 441-449.
50. McMichael, A.J.; Koff, W.C. Vaccines that stimulate T cell immunity to HIV-1: The next step. Nat. Immunol. 2014, 15, 319-322.
51. Manrique, M.; Kozlowski, P.A.; Cobo-Molinos, A.; Wang, S.W.; Wilson, R.L.; Montefiori, D.C.; Mansfield, K.G.; Carville, A.; Aldovini, A. Long-term control of simian immunodeficiency virus mac251 viremia to undetectable levels in half of infected female rhesus macaques nasally vaccinated with simian immunodeficiency virus DNA/recombinant modified vaccinia virus Ankara. J. Immunol. 2011, 186, 3581-3593.
52. Hansen, S.G.; Ford, J.C.; Lewis, M.S.; Ventura, A.B.; Hughes, C.M.; Coyne-Johnson, L.; Whizin, N.; Oswald, K.; Shoemaker, R.; Swanson, T.; et al. Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 2011, 473, 523-527.
53. Hansen, S.G.; Piatak, M., Jr.; Ventura, A.B.; Hughes, C.M.; Gilbride, R.M.; Ford, J.C.; Oswald, K.; Shoemaker, R.; Li, Y.; Lewis, M.S.; et al. Immune clearance of highly pathogenic SIV infection. Nature 2013, 502, 100-104.
54. Picker, L.J.; Hagen, S.I.; Lum, R.; Reed-Inderbitzin, E.F.; Daly, L.M.; Sylwester, A.W.; Walker, J.M.; Siess, D.C.; Piatak, M., Jr.; Wang, C.; et al. Insufficient Production and Tissue Delivery of CD4 Memory T Cells in Rapidly Progressive Simian Immunodeficiency Virus Infection. J. Exp. Med. 2004, 200, 1299-1314.
55. Shanmugasundaram, U.; Critchfield, J.W.; Panel, J.; Perry, J.; Giudice, L.C.; Smith-McCune, K.; Greenblatt, R.M.; Shacklett, B.L. Phenotype and functionality of CD4+ amd CD8+ T cells in the upper reproductive tract of healthy premenopausal women. Am. J. Reprod. Immunol. 2014, 71, 95-108.
56. Wira, C.R.; Fahey, J.V. A new strategy to understand how HIV infects women: Identification of a window of vulnerability during the menstrual cycle. AIDS 2008, 22, 1909-1917.
57. Wira, C.R.; Fahey, J.V.; Rodriguez-Garcia, M.; Shen, Z.; Patel, M.V. Regulation of mucosal immunity in the female reproductive tract: The fole of sex hormones in immune protection against sexually transmitted pathogens. Am. J. Reprod. Immunol. 2014, doi:10.1111/aji.12252.
58. McKinnon, L.R.; Hughes, S.M.; De rosa, S.C.; Martinson, J.A.; Plants, J.; Brady, K.E.; Gunbi, P.P.; Adams, D.J.; Vojtech, L.; Galloway, D.C.; et al. Optimizing viable leukocyte sampling from the female genital tract for clinical trials: An international multisite study. PLoS One 2014, 9, e85675.
59. Carias, A.M.; McCoombe, S.; McRaven, M.; Anderson, M.; Galloway, N.; Vandergrift, N.; Fought, A.J.; Lurain, J.; Duplantis, M.; Veazey, R.S.; et al. Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract. J. Virol. 2013, 87, 11388-11400.
60. Sui, Y.; Gagnon, S.; Dzutsev, A.; Zhu, Q.; Yu, H.; Hogg, A.; Wang, Y.; Xia, Z.; Belyakov, I.M.; Venzon, D.; et al. TLR agonists and/or IL-15 adjuvanted mucosal SIV vaccine reduced gut CD4+ memory T cell loss in SIVmac251-challenged rhesus macaques. Vaccine 2011, 30, 59-68.
61. Strbo, N.; Vaccari, M.; Pahwa, S.; Kolber, M.A.; Fisher, E.; Gonzalez, L.; Doster, M.N.; Hryniewicz, A.; Felber, B.K.; Pavlakis, G.N.; et al. Gp96SIVIg immunization induces potent polyepitope specific multifunctional memory responses in rectal and vaginal mucosa. Vaccine 2011, 29, 2619-2625.
62. Weaver, E.A.; Nehete, P.N.; Nehete, B.P.; Yang, G.; Buchl, S.J.; Hanley, P.W.; Palmer, D.; Montefiori, D.C.; Ferrari, G.; Ng, P.; et al. Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV. PLoS One 2013, 8, e67574.
63. Malkevitch, N.V.; Patterson, L.J.; Aldrich, M.K.; Wu, Y.; Venzon, D.; Florese, R.H.; Kalyanaraman, V.S.; Pal, R.; Lee, E.M.; Zhao, J.; et al. Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: Role of SIV-specific CD8+ T cell responses. Virology 2006, 353, 83-98.
64. Betts, M.R.; Nason, M.C.; West, S.M.; De Rosa, S.C.; Migueles, S.A.; Abraham, J.; Lederman, M.M.; Benito, J.M.; Goepfert, P.A.; Connors, M.; et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006, 107, 4781-4789.
65. Critchfield, J.W.; Lemongello, D.; Walker, D.H.; Garcia, J.C.; Asmuth, D.M.; Pollard, R.B.; Shacklett, B.L. Multifunctional human immunodeficiency virus (HIV) Gag-specific CD8+ T-cell responses in rectal mucosa and peripheral blood mononuclear cells during chronic HIV type 1 infection. J. Virol. 2007, 81, 5460-5471.
66. Varadarajan, N.; Kwon, D.S.; Law, K.M.; Ogunniyi, A.O.; Anahtar, M.N.; Richter, J.M.; Walker, B.D.; Love, J.C. Rapid, efficient functional characterization and recovery of HIV-specific human CD8+ T cells using microengraving. Proc. Natl. Acad. Sci. USA 2012, 109, 3885-3890.
67. Reeves, R.K.; Evans, T.I.; Gillis, J.; Wong, F.E.; Connole, M.; Carville, A.; Johnson, R.P. Quantification of mucosal mononuclear cells in tissues with a fluorescent bead-based polychromatic flow cytometry assay. J. Immunol. Methods. 2011, 367, 95-98.
68. Brandtzaeg, P.; Farstad, I.N.; Haraldsen, G. Regional specialization in the mucosal immune system: Primed cells do not always home along the same track. Immunol. Today 1999, 20, 267-277.
69. Chen, K.; Cerutti, A. Vaccination strategies to promote mucosal antibody responses. Immunity 2010, 33, 479-491.
70. Dlugonska, H.; Grzybowski, M. Mucosal vaccination--an old but still vital strategy. Ann. Parasitol. 2012, 58, 1-8.
71. Duerr, A. Update on mucosal HIV vaccine vectors. Curr. Opin. HIV AIDS 2010, 5, 397-403.
72. Azizi, A.; Ghunaim, H.; Diaz-Mitoma, F.; Mestecky, J. Mucosal HIV vaccines: A holy grail or a dud? Vaccine 2010, 28, 4015-4026.
73. Belyakov, I.M.; Ahlers, J.D. Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for development of protective HIV-1 vaccines. Curr. Med. Chem. 2011, 18, 3953-3962.
74. Gebril, A.; Alsaadi, M.; Acevedo, R.; Mullen, A.B.; Ferro, V.A. Optimizing efficacy of mucosal vaccines. Expert Rev. Vaccines 2012, 11, 1139-1155.
75. Zaman, M.; Chandrudu, S.; Toth, I. Strategies for intranasal delivery of vaccines. Drug Deliv. Transl. Res. 2013, 3, 100-109.
76. Lycke, N. Recent progress in mucosal vaccine development: Potential and limitations. Nat. Rev. Immunol. 2012, 12, 592-605.
77. Yu, M.; Vajdy, M. Mucosal HIV transmission and vaccination strategies through oral compared with vaginal and rectal routes. Expert Opin. Biol. Ther. 2010, 10, 1181-1195.
78. Stevceva, L.; Alvarez, X.; Lackner, A.A.; Tryniszewska, E.; Kelsall, B.; Nacsa, J.; Tartaglia, J.; Strober, W.; Franchini, G. Both mucosal and systemic routes of immunization with the live, attenuated NYVAC/simian immunodeficiency virus SIV(gpe) recombinant vaccine result in gag-specific CD8(+) T-cell responses in mucosal tissues of macaques. J. Virol. 2002, 76, 11659-11676.
79. Enose, Y.; Ui, M.; Miyake, A.; Suzuki, H.; Uesaka, H.; Kuwata, T.; Kunisawa, J.; Kiyono, H.; Takahashi, H.; Miura, T.; et al. Protection by intranasal immunization of a nef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV. Virology 2002, 298, 306-316.
80. Crotty, S.; Miller, C.J.; Lohman, B.L.; Neagu, M.R.; Compton, L.; Lu, D.; Lü, F.X.; Fritts, L.; Lifson, J.D.; Andino, R. Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors. J. Virol. 2001, 75, 7435-7452.
81. Patterson, L.J.; Malkevitch, N.; Venzon, D.; Pinczewski, J.; Gómez-Román, V.R.; Wang, L.; Kalyanaraman, V.S.; Markham, P.D.; Robey, F.A.; Robert-Guroff, M. Protection against mucosal simian immunodeficiency virus SIV(mac251) challenge by using replicating adenovirus-SIV multigene vaccine priming and subunit boosting. J. Virol. 2004, 78, 2212-2221.
82. Bogers, W.M.; Davis, D.; Baak, I.; Kan, E.; Hofman, S.; Sun, Y.; Mortier, D.; Lian, Y.; Oostermeijer, H.; Fagrouch, Z.; et al. Systemic neutralizing antibodies induced by long interval mucosally primed systemically boosted immunization correlate with protection from mucosal SHIV challenge. Virology 2008, 382, 217-225.
83. Patterson, L.J.; Kuate, S.; Daltabuit-Test, M.; Li, Q.; Xiao, P.; McKinnon, K.; DiPasquale, J.; Cristillo, A.; Venzon, D.; Haase, A.; et al. Replicating adenovirus-simian immunodeficiency virus (SIV) vectors efficiently prime SIV-specific systemic and mucosal immune responses by targeting myeloid dendritic cells and persisting in rectal macrophages, regardless of immunization route. Clin. Vaccine Immunol. 2012, 19, 629-637.
84. Manrique, M.; Micewicz, E.; Kozlowski, P.A.; Wang, S.W.; Aurora, D.; Wilson, R.L.; Ghebremichael, M.; Mazzara, G.; Montefiori, D.; Carville, A.; et al. DNA-MVA vaccine protection after X4 SHIV challenge in macaques correlates with day-of-challenge antiviral CD4+ cell-mediated immunity levels and postchallenge preservation of CD4+ T cell memory. AIDS Res. Hum. Retroviruses 2008, 24, 505-519.
85. Miyake, A.; Akagi, T.; Enose, Y.; Ueno, M.; Kawamura, M.; Horiuchi, R.; Hiraishi, K.; Adachi, M.; Serizawa, T.; Narayan, O.; et al. Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques. J. Med. Virol. 2004, 73, 368-377.
86. Barnett, S.W.; Srivastava, I.K.; Kan, E.; Zhou, F.; Goodsell, A.; Cristillo, A.D.; Ferrari, M.G.; Weiss, D.E.; Letvin, N.L.; Montefiori, D.; et al. Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope. AIDS 2008, 22, 339-348.
87. Lü, F.X.; Jacobson, R.S. Oral mucosal immunity and HIV/SIV infection. J. Dent. Res. 2007, 86, 216-226.
88. Demberg, T.; Robert-Guroff, M. Mucosal immunity and protection against HIV/SIV infection: Strategies and challenges for vaccine design. Int. Rev. Immunol. 2009, 28, 20-48.
89. Zhou, Q.; Hidajat, R.; Peng, B.; Venzon, D.; Aldrich, M.K.; Richardson, E.; Lee, E.M.; Kalyanaraman, V.S.; Grimes, G.; Gómez-Román, V.R.; et al. Comparative evaluation of oral and intranasal priming with replication-competent adenovirus 5 host range mutant (Ad5hr)-simian immunodeficiency virus (SIV) recombinant vaccines on immunogenicity and protective efficacy against SIV (mac251). Vaccine 2007, 25, 8021-8035.
90. Zhao, J.; Lou, Y.; Pinczewski, J.; Malkevitch, N.; Aldrich, K.; Kalyanaraman, V.S.; Venzon, D.; Peng, B.; Patterson, L.J.; Edghill-Smith, Y.; et al. Boosting of SIV-specific immune responses in rhesus macaques by repeated administration of Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinants. Vaccine 2003, 21, 4022-4035.
91. Patterson, L.J.; Beal, J.; Demberg, T.; Florese, R.H.; Malkevich, N.; Venzon, D.; Aldrich, K.; Richardson, E.; Kalyanaraman, V.S.; Kalisz, I.; et al. Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV89.6P challenge in Mamu-A*01 negative rhesus macaques. Virology 2008, 374, 322-337.
92. Kubota, M.; Miller, C.J.; Imaoka, K.; Kawabata, S.; Fujihashi, K.; McGhee, J.R.; Kiyono, H. Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates. J. Immunol. 1997, 158, 5321-5319.
93. Sun, C.; Chen, Z.; Tang, X.; Zhang, Y.; Feng, L.; Du, Y.; Xiao, L.; Liu, L.; Zhu, W.; Chen, L.; et al. Mucosal priming with a replicating-vaccinia virus-based vaccine elicits protective immunity to simian immunodeficiency virus challenge in rhesus monkeys. J. Virol. 2013, 87, 5669-5677.
94. Manrique, M.; Kozlowski, P.A.; Cobo-Molinos, A.; Wang, S.W.; Wilson, R.L.; Montefiori, D.C.; Carville, A.; Aldovini, A. Immunogenicity of a vaccine regimen composed of simian immunodeficiency virus DNA, rMVA, and viral particles administered to female rhesus macaques via four different mucosal routes. J. Virol. 2013, 87, 4738-4750.
95. Cuburu, N.; Kweon, M.N.; Song, J.H.; Hervouet, C.; Luci, C.; Sun, J.B.; Hofman, P.; Holmgren, J.; Anjuère, F.; Czerkinsky, C. Sublingual immunization induces broad-based systemic and mucosal immune responses in mice. Vaccine 2007, 25, 8598-8610.
96. Song, J.H.; Nguyen, H.H.; Cuburu, N.; Horimoto, T.; Ko, S.Y.; Park, S.H.; Czerkinsky, C.; Kweon, M.N. Sublingual vaccination with influenza virus protects mice against lethal viral infection. Proc. Natl. Acad. Sci. USA 2008, 105, 1644-1649.
97. Hervouet, C.; Luci, C.; Cuburu, N.; Cremel, M.; Bekri, S.; Vimeux, L.; Marañon, C.; Czerkinsky, C.; Hosmalin, A.; Anjuère, F. Sublingual immunization with an HIV subunit vaccine induces antibodies and cytotoxic T cells in the mouse female genital tract. Vaccine 2010, 28, 5582-5590.
98. Appledorn, D.M.; Aldhamen, Y.A.; Godbehere, S.; Seregin, S.S.; Amalfitano, A. Sublingual administration of an adenovirus serotype 5 (Ad5)-based vaccine confirms Toll-like receptor agonist activity in the oral cavity and elicits improved mucosal and systemic cell-mediated responses against HIV antigens despite preexisting Ad5 immunity. Clin. Vaccin. Immunol. 2011, 18, 150-160.
99. Stahl-Hennig, C.; Kuate, S.; Franz, M.; Suh, Y.S.; Stoiber, H.; Sauermann, U.; Tenner-Racz, K.; Norley, S.; Park, K.S.; Sung, Y.C.; et al. Atraumatic oral spray immunization with replication-deficient viral vector vaccines. J. Virol. 2007, 81, 13180-13190.
100. Earl, P.L.; Americo, J.L.; Wyatt, L.S.; Eller, L.A.; Montefiori, D.C.; Byrum, R.; Piatak, M.; Lifson, J.D.; Amara, R.R.; Robinson, H.L.; et al. Recombinant modified vaccinia virus Ankara provides durable protection against disease caused by an immunodeficiency virus as well as long-term immunity to an orthopoxvirus in a non-human primate. Virology 2007, 366, 84-97.
101. Stolte-Leeb, N.; Bieler, K.; Kostler, J.; Heeney, J.; Haaft, P.T.; Suh, Y.S.; Hunsmann, G.; Stahl-Hennig, C.; Wagner, R. Better protective effects in rhesus macaques by combining systemic and mucosal application of a dual component vector vaccine after rectal SHIV89.6P challenge compared to systemic vaccination alone. Viral Immunol. 2008, 21, 235-246.
102. Schulte, R.; Suh, Y.S.; Sauermann, U.; Ochieng, W.; Sopper, S.; Kim, K.S.; Ahn, S.S.; Park, K.S.; Stolte-Leeb, N.; Hunsmann, G.; et al. Mucosal prior to systemic application of recombinant adenovirus boosting is more immunogenic than systemic application twice but confers similar protection against SIV-challenge in DNA vaccine-primed macaques. Virology 2009, 383, 300-309.
103. Tenner-Racz, K.; Stahl Hennig, C.; Uberla, K.; Stoiber, H.; Ignatius, R.; Heeney, J.; Steinman, R.M.; Racz, P. Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus. Proc. Natl. Acad. Sci. USA 2004, 101, 3017-3022.
104. Vagenas, P.; Williams, V.G.; Piatak, M., Jr.; Bess, J.W., Jr.; Lifson, J.D.; Blanchard, J.L.; Gettie, A.; Robbiani, M. Tonsillar application of AT-2 SIV affords partial protection against rectal challenge with SIVmac239. J. Acquir. Immun. Defic. Syndr. 2009, 52, 433-442.
105. Randall, T.D. Bronchus-associated lymphoid tissue (BALT) structure and function. Adv. Immunol. 2010, 107, 187-241.
106. Bienenstock, J.; McDermott, M.R. Bronchus-and nasal-associated lymphoid tissues. Immunol. Rev. 2005, 206, 22-31.
107. Marx, P.A.; Compans, R.W.; Gettie, A.; Staas, J.K.; Gilley, R.M.; Mulligan, M.J.; Yamshchikov, G.V.; Chen, D.; Eldridge, J.H. Protection against vaginal transmission with microencapsulated vaccine. Science 1993, 260, 1323-1327.
108. Demberg, T.; Boyer, J.D.; Malkevich, N.; Patterson, L.J.; Venzon, D.; Summers, E.L.; Kalisz, I.; Kalyanaraman, V.; Lee, E.M.; Weiner, D.B.; et al. Sequential priming with simian immunodeficiency virus (SIV) DNA vaccines, with or without encoded cytokines, and a replicating adenovirus-SIV recombinant followed by protein boosting does not control a pathogenic SIVmac251 mucosal challenge. J. Virol. 2008, 82, 10911-10921.
109. Belyakov, I.M.; Hel, Z.; Kelsall, B.; Kuznetsov, V.A.; Ahlers, J.D.; Nacsa, J.; Watkins, D.I.; Allen, T.M.; Sette, A.; Altman, J.; et al. Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques. Nat. Med. 2001, 7, 1320-1326.
110. Wang, S.W.; Bertley, F.M.; Kozlowski, P.A.; Herrmann, L.; Manson, K.; Mazzara, G.; Piatak, M.; Johnson, R.P.; Carville, A.; Mansfield, K.; et al. An SHIV DNA/MVA rectal vaccination in macaques provides systemic and mucosal virus-specific responses and protection against AIDS. AIDS Res. Hum. Retrovir 2004, 20, 846-859.
111. Belyakov, I.M.; Kuznetsov, V.A.; Kelsall, B.; Klinman, D.; Moniuszko, M.; Lemon, M.; Markham, P.D.; Pal, R.; Clements, J.D.; Lewis, M.G.; et al. Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosa. Blood 2006, 107, 3258-3264.
112. Sui, Y.; Zhu, Q.; Gagnon, S.; Dzutsev, A.; Terabe, M.; Vaccari, M.; Venzon, D.; Klinman, D.; Strober, W.; Kelsall, B.; et al. Innate and adaptive immune correlates of vaccine and adjuvant-induced control of mucosal transmission of SIV in macaques. Proc. Natl. Acad. Sci. USA 2010, 107, 9843-9848.
113. Cranage, M.P.; Fraser, C.A.; Cope, A.; McKay, P.F.; Seaman, M.S.; Cole, T.; Mahmoud, A.N.; Hall, J.; Giles, E.; Voss, G.; et al. Antibody responses after intravaginal immunization with trimeric HIV-1 CN54 clade C gp140 in Carbopol gel are augmented by systemic priming or boosting with an adjuvanted formulation. Vaccine 2011, 29, 1421-1430.
114. Haase, A.T. Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu. Rev. Med. 2011, 62, 127-139.
115. Kozlowski, P.A.; Neutra, M.R. The role of mucosal immunity in prevention of HIV transmission. Curr. Mol. Med. 2003, 3, 217-228.
116. Shen, R.; Smith, P.D. Mucosal Correlates of Protection in HIV-1-Exposed Sero-negative Persons. Am. J. Reprod. Immunol. 2014, doi:10.1111/aji.12202.
117. Daniel, M.D.; Kirchhoff, F.; Czajak, S.C.; Sehgal, P.K.; Desrosiers, R.C. Protective Effects of a Live Attenuated SIV Vaccine with a Deletion in the nef Gene. Science 1992, 258, 1938-1941.
118. Johnson, R.P.; Desrosiers, R.C. Protective immunity induced by live attenuated simian immunodeficiency virus. Curr. Opin. Immunol. 1998, 10, 436-443.
119. Sasikala-Appukuttan, A.K.; Kim, H.O.; Kinzel, N.J.; Hong, J.J.; Smith, A.J.; Wagstaff, R.; Reilly, C.; Piatak, M., Jr.; Lifson, J.D.; Reeves, R.K.; et al. Location and dynamics of the immunodominant CD8 T cell response to SIV. nef immunization and SIVmac251 vaginal challenge. PLoS One 2013, 8, e81623.
120. Genesca, M.; Skinner, P.J.; Hong, J.J.; Li, J.; Lu, D.; McChesney, M.B.; Miller, C.J. With minimal systemic-cell expansion, CD8+ T cells mediate protection of rhesus macaques immunized with attenuated simian-human immunodeficiency virus SHIV89.6 from vaginal challenge with simian immunodeficiency virus. J. Virol. 2008, 82, 11181-11196.
121. Genesca, M.; Ma, Z.M.; Wang, Y.; Assaf, B.; Qureshi, H.; Fritts, L.; Huang, Y.; McChesney, M.B.; Miller, C.J. Live-attenuated lentivirus immunization modulates innate immunity and inflammation while protecting rhesus macaques from vaginal simian immunodeficiency virus challenge. J. Virol. 2012, 86, 9188-9200.
122. Hansen, S.G.; Sacha, J.B.; Hughes, C.M.; Ford, J.C.; Burwitz, B.J.; Scholz, I.; Gilbride, R.M.; Lewis, M.S.; Gilliam, A.N.; Ventura, A.B.; et al. Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science 2013, 340, 1237874.
123. Barouch, D.H.; Liu, J.; Li, H.; Maxfield, L.F.; Abbink, P.; Lynch, D.M.; Iampietro, M.J.; SanMiguel, A.; Seaman, M.S.; Ferrari, G.; et al. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature 2012, 482, 89-93.
124. Wilson, N.A.; Reed, J.; Napoe, G.S.; Piaskowski, S.; Szymanski, A.; Furlott, J.; Gonzalez, E.J.; Yant, L.J.; Maness, N.J.; May, G.E.; et al. Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239. J. Virol. 2006, 80, 5875-5885.
125. Hel, Z.; Nacsa, J.; Tryniszewska, E.; Tsai, W.P.; Parks, R.W.; Montefiori, D.C.; Felber, B.K.; Tartaglia, J.; Pavlakis, G.N.; Franchini, G. Containment of simian immunodeficiency virus infection in vaccinated macaques: Correlation with the magnitude of virus-specific pre-and postchallenge CD4+ and CD8+ T cell responses. J. Immunol. 2002, 169, 4778-4787.
126. Boyer, J.D.; Maciag, P.C.; Parkinson, R.; Wu, L.; Lewis, M.G.; Weiner, D.B.; Paterson, Y. Rhesus macaques with high levels of vaccine induced IFN-gamma producing cells better control viral set-point following challenge with SIV239. Vaccine 2006, 24, 4498-4502.
127. Rosati, M.; Bergamaschi, C.; Valentin, A.; Kulkarni, V.; Jalah, R.; Alicea, C.; Patel, V.; von Gegerfelt, A.S.; Montefiori, D.C.; Venzon, D.J.; et al. DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge. Proc. Natl. Acad. Sci. USA 2009, 6, 15831-15836.
128. Patel, V.; Jalah, R.; Kulkarni, V.; Valentin, A.; Rosati, M.; Alicea, C.; von Gegerfelt, A.; Huang, W.; Guan, Y.; Keele, B.F.; et al. DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous SIV challenge. Proc. Natl. Acad. Sci. USA 2013, 110, 2975-2980.
129. Barnett, S.W.; Burke, B.; Sun, Y.; Kan, E.; Legg, H.; Lian, Y.; Bost, K.; Zhou, F.; Goodsell, A.; Zur Megede, J.; et al. Antibody-mediated protection against mucosal simian-human immunodeficiency virus challenge of macaques immunized with alphavirus replicon particles and boosted with trimeric envelope glycoprotein in MF59 adjuvant. J. Virol. 2010, 84, 5975-5985.
130. Lai, L.; Kwa, S.F.; Kozlowski, P.A.; Montefiori, D.C.; Nolen, T.L.; Hudgens, M.G.; Johnson, W.E.; Ferrari, G.; Hirsch, V.M.; Felber, B.K.; et al. SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses. Vaccine 2012, 30, 1737-1745.
131. Lai, L.; Kwa, S.; Kozloski, P.A.; Montefiori, C.; Ferrari, G.; Johnson, W.E.; Hirsch, V.; Villinger, F.; Chennareddi, L.; Earl, P.L.; et al. Prevention of infeciton by a granulocyte-macrophage colony-stimulating factor co-expressing DNA/modified vaccinia Ankara simian immunodeficiency virus vaccine. J. Infect. Dis. 2011, 204, 164-173.
132. Pegu, P.; Vaccari, M.; Gordon, S.; Keele, B.F.; Doster, M.; Guan, Y.; Ferrari, G.; Pal, R.; Ferrari, M.G.; Whitney, S.; et al. Antibodies with high avidity to the gp120 envelope protein in protection from sisian immunodeficiency virus SIV (mac251) acquisition in an immunization regimen that mimics the RV-144 Thai trial. J. Virol. 2013, 87, 1708-1719.
133. Gomez-Roman, V.R.; Patterson, L.J.; Venzon, D.; Liewehr, D.; Aldrich, K.; Florese, R.; Robert-Guroff, M. Vaccine-elicited antibodies mediate antibody-dependent cellular cytotoxicity correlated with significantly reduced acute viremia in rhesus macaques challenged with SIVmac251. J. Immunol. 2005, 174, 2185-2189.
134. Florese, R.H.; Demberg, T.; Xiao, P.; Kuller, L.; Larsen, K.; Summers, L.E.; Venzon, D.; Cafaro, A.; Ensoli, B.; Robert-Guroff, M. Contribution of Nonneutralizing Vaccine-Elicited Antibody Activities to Improved Protective Efficacy in Rhesus Macaques Immunized with Tat/Env Compared with Multigenic Vaccines. J. Immunol. 2009, 182, 3718-3727.
135. Alpert, M.D.; Harvey, J.D.; Lauer, W.A.; Reeves, R.K.; Piatak, M., Jr.; Carbille, A.; Mansfield, K.G.; Lifson, J.D.; Li, W.; Desrosiers, R.C.; et al. ADCC develops over time during persistent infection with live-attenuated SIV and is associated with complete protection against SIVmac251 challenge. PLoS Pathog. 2012, 8, e1002890.
136. Forthal, D.N.; Landucci, G.; Keenan, B. Relationship between antibody-dependent cellular cytotoxicity, plasma HIV type 1 RNA, and CD4+ lymphocyte count. AIDS Res. Hum. Retroviruses 2001, 17, 553-561.
137. Forthal, D.N.; Landucci, G.; Cole, K.S.; Marthas, M.; Becerra, J.C.; Van Rompay, K. Rhesus macaque polyclonal and monoclonal antibodies inhibit simian immunodeficiency virus in the presence of human or autologous rhesus effector cells. J. Virol. 2006, 80, 9217-9215.
138. Bomsel, M. Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier. Nat. Med. 1997, 3, 42-47.
139. Brocca-Cofano, E.; McKinnon, K.; Demberg, T.; Venzon, D.; Hidajat, R.; Xiao, P.; Daltabuit-Test, M.; Patterson, L.J.; Robert-Guroff, M. Vaccine-elicited SIV and HIV envelope-specific IgA and IgG memory B cells in rhesus macaque peripheral blood correlate with functional antibody responses and reduced viremia. Vaccine 2011, 29, 3310-3319.
140. Tuero, I.; Vargas-Inchaustegui, D.; Musich, T.; Kalisz, I.; Kalyanaraman, V.S.; Pal, R.; LaBranche, C.; Montefiori, D.C.; Barnett, S.W.; Robert-Guroff, M. SIV Trimeric vs. Monomeric Env-Induced Antibody and Delayed SIV Acquisition in Vaccine Female Rhesus Macaques. HIV Vaccines: Adaptive Immunity and Beyond. Abstract. Keystone Symposium 2014, Banff, Alberta, CA, USA, 2014.
141. HIV/AIDS. HIV/AIDS Fact sheet N°360. Available online: http://www.who.int/mediacentre/ factsheets/fs360/en/ (accessed on 15 May 2014).
142. Rerks-Ngarm, S.; Pitisuttithum, P.; Nitayaphan, S.; Kaewkungwal, J.; Chiu, J.; Paris, R.; Premsri, N.; Namwat, C.; de Souza, M.; Adams, E.; Benenson, M.; et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl J. Med. 2009, 361, 2209-2220.
143. Clinical Trials. Available online: http://www.clinicaltrials.gov/ (accessed 15 May 2014).
144. Cranage, M.P.; Fraser, C.A.; Stevens, Z.; Huting, J.; Chang, M.; Jeffs, S.A.; Seaman, M.S.; Cope, A.; Cole, T.; Shattock, R.J. Repeated vaginal administration of trimeric HIV-1 clade C gp140 induces serum and mucosal antibody responses. Mucosal Immunol. 2012, 3, 57-68.
145. Curran, R.M.; Donnelly, L.; Morrow, R.J.; Fraser, C.; Andrews, G.; Cranage, M.; Malcolm, R.K.; Shattock, R.J.; Woolfson, A.D. Vaginal delivery of the recombinant HIV-1 clade C trimeric gp140 envelope protein CN54gp140 within novel rheologically structured vehicles elicts specific immune responses. Vaccine 2009, 27, 6791-6798.
146. Gurwith, M.; Lock, M.; Taylor, E.M.; Ishioka, G.; Alexander, J.; Mayall, T.; Ervin, J.E.; Greenberg, R.N.; Strout, C.; Treanor, J.J.; et al. Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: A randomised, double-blind, placebo-controlled, phase 1 study. Lancet Infect. Dis. 2013, 13, 238-250.
147. Alexander, J.; Mendy, J.; Vang, L.; Avanzini, J.B.; Garduno, F.; Manayani, D.J.; Ishioka, G.; Farness, P.; Ping, L.H.; Swanstrom, R.; et al. Pre-Clinical Development of a Recombinant, Replication-Competent Adenovirus Serotype 4 Vector Vaccine Expressing HIV-1 Envelope 1086 Clade C. PLoS One 2013, 8, e82380.
148. Ploquin, M.J.; Jacquelin, B.; Jochems S.P.; Barré-Sinoussi, F.; Müller-Trutwin, M.C. Innate immunity in the control of HIV/AIDS: Recent advances and open questions. AIDS 2012, 26, 1269-1279.
149. Ahmed, R.K.; Biberfeld, G.; Thorstensson, R. Innate immunity in experimental SIV infection and vaccination. Mol. Immunol. 2005, 42, 251-258.