HIV Vaccination: Turning the Spotlight on Effector Memory T Cells As Mucosal Gatekeepers

Overview

Journal F1000 Biol Rep

Specialty Biology

Date 2010 Jan 5

PMID 20046812

Authors

Hilde Cheroutre

Affiliations

Soon will be listed here.

Abstract

The accumulating failures in HIV vaccine development demonstrate that the immunization approaches used so far are insufficient to reproduce the naturally occurring immunity that controls the virus in long-term non-progressors, HIV controllers, and continuously exposed sex workers. They also underscore the desperate need for new approaches in the design of more effective vaccination protocols. Recent findings might have brought us closer to that goal by providing proof of concept for a novel preventative HIV vaccine by establishing CD8 effector memory T cells within the mucosal sites of transmission.

References

Hutnick N, Carnathan D, Dubey S, Makedonas G, Cox K, Kierstead L . Baseline Ad5 serostatus does not predict Ad5 HIV vaccine-induced expansion of adenovirus-specific CD4+ T cells. Nat Med. 2009; 15(8):876-8. PMC: 2723179. DOI: 10.1038/nm.1989. View

Patterson L, Malkevitch N, Venzon D, Pinczewski J, Gomez-Roman V, Wang L . Protection against mucosal simian immunodeficiency virus SIV(mac251) challenge by using replicating adenovirus-SIV multigene vaccine priming and subunit boosting. J Virol. 2004; 78(5):2212-21. PMC: 369221. DOI: 10.1128/jvi.78.5.2212-2221.2004. View

Brenchley J, Schacker T, Ruff L, Price D, Taylor J, Beilman G . CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004; 200(6):749-59. PMC: 2211962. DOI: 10.1084/jem.20040874. View

Schmitz J, Kuroda M, Santra S, Sasseville V, Simon M, Lifton M . Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science. 1999; 283(5403):857-60. DOI: 10.1126/science.283.5403.857. View

Jin X, Bauer D, Tuttleton S, Lewin S, Gettie A, Blanchard J . Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med. 1999; 189(6):991-8. PMC: 2193038. DOI: 10.1084/jem.189.6.991. View

Schmitz J, Johnson R, McClure H, Manson K, Wyand M, Kuroda M . Effect of CD8+ lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3-vaccinated rhesus macaques. J Virol. 2005; 79(13):8131-41. PMC: 1143721. DOI: 10.1128/JVI.79.13.8131-8141.2005. View

Sekaly R . The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development?. J Exp Med. 2008; 205(1):7-12. PMC: 2234358. DOI: 10.1084/jem.20072681. View

OBrien K, Liu J, King S, Sun Y, Schmitz J, Lifton M . Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans. Nat Med. 2009; 15(8):873-5. PMC: 2756115. DOI: 10.1038/nm.1991. View

Veazey R, Demaria M, Chalifoux L, Shvetz D, Pauley D, Knight H . Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science. 1998; 280(5362):427-31. DOI: 10.1126/science.280.5362.427. View

10.

Vogel T, Reynolds M, Fuller D, Vielhuber K, Shipley T, Fuller J . Multispecific vaccine-induced mucosal cytotoxic T lymphocytes reduce acute-phase viral replication but fail in long-term control of simian immunodeficiency virus SIVmac239. J Virol. 2003; 77(24):13348-60. PMC: 296068. DOI: 10.1128/jvi.77.24.13348-13360.2003. View

11.

Li Q, Duan L, Estes J, Ma Z, Rourke T, Wang Y . Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature. 2005; 434(7037):1148-52. DOI: 10.1038/nature03513. View

12.

Raffatellu M, Santos R, Verhoeven D, George M, Wilson R, Winter S . Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008; 14(4):421-8. PMC: 2901863. DOI: 10.1038/nm1743. View

13.

Daucher M, Price D, Brenchley J, Lamoreaux L, Metcalf J, Rehm C . Virological outcome after structured interruption of antiretroviral therapy for human immunodeficiency virus infection is associated with the functional profile of virus-specific CD8+ T cells. J Virol. 2008; 82(8):4102-14. PMC: 2292997. DOI: 10.1128/JVI.02212-07. View

14.

Lu S . Human versus HIV: round 2 defeat in AIDS vaccine development. Expert Rev Vaccines. 2008; 7(2):151-3. DOI: 10.1586/14760584.7.2.151. View

15.

Belyakov I, Kuznetsov V, Kelsall B, Klinman D, Moniuszko M, Lemon M . Impact of vaccine-induced mucosal high-avidity CD8+ CTLs in delay of AIDS viral dissemination from mucosa. Blood. 2005; 107(8):3258-64. PMC: 1895757. DOI: 10.1182/blood-2005-11-4374. View

16.

Matano T, Shibata R, Siemon C, Connors M, Lane H, Martin M . Administration of an anti-CD8 monoclonal antibody interferes with the clearance of chimeric simian/human immunodeficiency virus during primary infections of rhesus macaques. J Virol. 1998; 72(1):164-9. PMC: 109361. DOI: 10.1128/JVI.72.1.164-169.1998. View

17.

Kawada M, Tsukamoto T, Yamamoto H, Takeda A, Igarashi H, Watkins D . Long-term control of simian immunodeficiency virus replication with central memory CD4+ T-cell preservation after nonsterile protection by a cytotoxic T-lymphocyte-based vaccine. J Virol. 2007; 81(10):5202-11. PMC: 1900223. DOI: 10.1128/JVI.02881-06. View

18.

Hansen S, Vieville C, Whizin N, Coyne-Johnson L, Siess D, Drummond D . Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat Med. 2009; 15(3):293-9. PMC: 2720091. DOI: 10.1038/nm.1935. View

19.

Gallo R, SARIN P, Gelmann E, Robert-Guroff M, Richardson E, Kalyanaraman V . Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983; 220(4599):865-7. DOI: 10.1126/science.6601823. View

20.

Pantaleo G . HIV-1 T-cell vaccines: evaluating the next step. Lancet Infect Dis. 2007; 8(2):82-3. DOI: 10.1016/S1473-3099(07)70266-9. View