1887

Abstract

Genetic, epidemiological and experimental evidence suggest that the major histocompatibility complex (MHC) is critical in controlling human immunodeficiency virus (HIV) infection. The objectives of this study were to determine whether novel recombinant Mamu MHC constructs would elicit protection against rectal challenge with heterologous simian–human immunodeficiency virus (SHIV) strain SF162.P4 in rhesus macaques. Mamu class I and II gene products were linked together with HIV gp140, simian immunodeficiency virus (SIV) p27 and heat-shock protein 70 to dextran. The vaccine was administered to two groups, each consisting of nine macaques, either subcutaneously (SC), or rectally and boosted by SC immunization. The controls were untreated or adjuvant-treated animals. Repetitive rectal challenges with up to ten doses of SHIV SF162.P4 showed a significant decrease in the peak and sequential viral RNA concentrations, and three macaques remained uninfected, in the nine SC-immunized animals, compared with infection in all nine controls. Macaques immunized rectally followed by SC boosters showed a less significant decrease in both sequential and peak viral loads compared with the SC-immunized animals, and all were infected following rectal challenge with SHIV SF162.P4. Plasma and mucosal IgG and IgA antibodies to Mamu class I alleles and HIV gp120, as well as to RANTES (regulated upon activation, normal T-cell expressed, and secreted; CCR5) were increased, and showed significant inverse correlations with the peak viral load. These results suggested that allo-immunization with recombinant MHC constructs linked to HIV–SIV antigens merits further investigation in preventing HIV-1 infection.

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2012-07-01
2020-01-27
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References

  1. Arthur L. O., Bess J. W. Jr, Urban R. G., Strominger J. L., Morton W. R., Mann D. L., Henderson L. E., Benveniste R. E.. ( 1995;). Macaques immunized with HLA-DR are protected from challenge with simian immunodeficiency virus. . J Virol 69:, 3117–3124.[PubMed]
    [Google Scholar]
  2. Babaahmady K., Oehlmann W., Singh M., Lehner T.. ( 2007;). Inhibition of human immunodeficiency virus type 1 infection of human CD4+ T cells by microbial HSP70 and the peptide epitope 407–426. . J Virol 81:, 3354–3360. [CrossRef][PubMed]
    [Google Scholar]
  3. Bergmeier L. A., Babaahmady K., Wang Y., Lehner T.. ( 2005;). Mucosal alloimmunization elicits T-cell proliferation, CC chemokines, CCR5 antibodies and inhibition of simian immunodeficiency virus infectivity. . J Gen Virol 86:, 2231–2238. [CrossRef][PubMed]
    [Google Scholar]
  4. Bogers W. M., Bergmeier L. A., Ma J., Oostermeijer H., Wang Y., Kelly C. G., Ten Haaft P., Singh M., Heeney J. L., Lehner T.. ( 2004;). A novel HIV-CCR5 receptor vaccine strategy in the control of mucosal SIV/HIV infection. . AIDS 18:, 25–36. [CrossRef][PubMed]
    [Google Scholar]
  5. Carlson J. R., McGraw T. P., Keddie E., Yee J. L., Rosenthal A., Langlois A. J., Dickover R., Donovan R., Luciw P. A.. & other authors ( 1990;). Vaccine protection of rhesus macaques against simian immunodeficiency virus infection. . AIDS Res Hum Retroviruses 6:, 1239–1246.[PubMed]
    [Google Scholar]
  6. Carrington M., O’Brien S. J.. ( 2003;). The influence of HLA genotype on AIDS. . Annu Rev Med 54:, 535–551. [CrossRef][PubMed]
    [Google Scholar]
  7. Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D.. ( 1989;). Vaccine protection against simian immunodeficiency virus infection. . Proc Natl Acad Sci U S A 86:, 6353–6357. [CrossRef][PubMed]
    [Google Scholar]
  8. Dormont D., Le Grand R., Carange M., Grennaway P., Hunsmann G., Stahl-Hennig C., Rossi G., Verani P., Stott J.. & other authors ( 1995;). Protection of macaques against simian immunodeficiency virus infection with activated vaccines. Comparison of adjuvants, doses and challenge viruses. . Vaccine 13:, 295–300.
    [Google Scholar]
  9. Gilbert P., Wang M., Wrin T., Petropoulos C., Gurwith M., Sinangil F., D’Souza P., Rodriguez-Chavez I. R., DeCamp A.. & other authors ( 2010;). Magnitude and breadth of a nonprotective neutralizing antibody response in an efficacy trial of a candidate HIV-1 gp120 vaccine. . J Infect Dis 202:, 595–605. [CrossRef][PubMed]
    [Google Scholar]
  10. Goulder P. J., Watkins D. I.. ( 2008;). Impact of MHC class I diversity on immune control of immunodeficiency virus replication. . Nat Rev Immunol 8:, 619–630. [CrossRef][PubMed]
    [Google Scholar]
  11. International HIV Controllers Study ( 2010;). The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. . Science 330:, 1551–1557. [CrossRef][PubMed]
    [Google Scholar]
  12. Kind C., Nadal D., Wyler C.-A., Siegrist C.-A., Cheseaux J. J., Vaudaux B., Fawer C.-L., Rudin C., Schaad U. B.. & other authors ( 1995;). Mother-to-child transmission of human immunodeficiency virus type 1: influence of parity and mode of delivery. . Eur J Pediatr 154:, 542–545. [CrossRef][PubMed]
    [Google Scholar]
  13. Kingsley C., Peters B., Babaahmady K., Pomeroy L., Rahman D., Vaughan R., Lehner T.. ( 2009;). Heterosexual and homosexual partners practising unprotected sex may develop allogeneic immunity and to a lesser extent tolerance. . PLoS ONE 4:, e7938. [CrossRef][PubMed]
    [Google Scholar]
  14. Langlois A. J., Weinhold K. J., Matthews T. J., Greenberg M. L., Bolognesi D. P.. ( 1992;). The ability of certain SIV vaccines to provoke reactions against normal cells. . Science 255:, 292–293. [CrossRef][PubMed]
    [Google Scholar]
  15. Lehner T., Bergmeier L. A., Tao L., Panagiotidi C., Klavinskis L. S., Hussain L., Ward R. G., Meyers N., Adams S. E.. & other authors ( 1994;). Targeted lymph node immunization with simian immunodeficiency virus p27 antigen to elicit genital, rectal, and urinary immune responses in nonhuman primates. . J Immunol 153:, 1858–1868.[PubMed]
    [Google Scholar]
  16. Lehner T., Shearer G. M., Hackett C. J., Schultz A., Sharma O. K.. ( 2000;). Alloimmunization as a strategy for vaccine design against HIV/AIDS. . AIDS Res Hum Retroviruses 16:, 309–313. [CrossRef][PubMed]
    [Google Scholar]
  17. Leith J. G., Clark D. A., Matthews T. J., Rosenthal K. L., Luscher M. A., Barber B. H., MacDonald K. S.. ( 2003;). Assessing human alloimmunization as a strategy for inducing HIV type 1 neutralizing anti-HLA responses. . AIDS Res Hum Retroviruses 19:, 957–965. [CrossRef][PubMed]
    [Google Scholar]
  18. MacDonald K. S., Embree J., Njenga S., Nagelkerke N. J., Ngatia I., Mohammed Z., Barber B. H., Ndinya-Achola J., Bwayo J., Plummer F. A.. ( 1998;). Mother–child class I HLA concordance increases perinatal human immunodeficiency virus type 1 transmission. . J Infect Dis 177:, 551–556. [CrossRef][PubMed]
    [Google Scholar]
  19. Mitchell E. A., Bergmeier L. A., Doyle C., Brookes R., Hussain L. A., Wang Y., Lehner T.. ( 1998;). Homing of mononuclear cells from iliac lymph nodes to the genital and rectal mucosa in non-human primates. . Eur J Immunol 28:, 3066–3074. [CrossRef][PubMed]
    [Google Scholar]
  20. Mörner A., Jansson M., Bunnik E. M., Schøller J., Vaughan R., Wang Y., Montefiori D. C., Otting N., Bontrop R.. & other authors ( 2011;). Immunization with recombinant HLA classes I and II, HIV-1 gp140, and SIV p27 elicits protection against heterologous SHIV infection in rhesus macaques. . J Virol 85:, 6442–6452. [CrossRef][PubMed]
    [Google Scholar]
  21. Murphey-Corb M., Martin L. N., Davison-Fairburn B., Montelaro R. C., Miller M., West M., Ohkawa S., Baskin G. B., Zhang J. Y.. & other authors ( 1989;). A formalin-inactivated whole SIV vaccine confers protection in macaques. . Science 246:, 1293–1297. [CrossRef][PubMed]
    [Google Scholar]
  22. Otting N., Mörner A., Bontrop R. E.. ( 2011;). Novel major histocompatibility complex class I alleles extracted from two rhesus macaque populations. . Tissue Antigens 77:, 79–80. [CrossRef][PubMed]
    [Google Scholar]
  23. Peters B., Whittall T., Babaahmady K., Gray K., Vaughan R., Lehner T.. ( 2004;). Effect of heterosexual intercourse on mucosal alloimmunisation and resistance to HIV-1 infection. . Lancet 363:, 518–524. [CrossRef][PubMed]
    [Google Scholar]
  24. Polyanskaya N., Sharpe S., Cook N., Leech S., Banks J., Dennis M., Hall G., Stott J., Cranage M.. ( 1997;). Anti-major histocompatibility complex antibody responses to simian B cells do not protect macaques against SIVmac infection. . AIDS Res Hum Retroviruses 13:, 923–931. [CrossRef][PubMed]
    [Google Scholar]
  25. Qiu C.-L., Yang G.-B., Yu K., Li Y., Li X.-L., Liu Q., Zhao H., Xing H., Shao Y.. ( 2008;). Characterization of the major histocompatibility complex class II DQB (MhcMamu-DQB1) alleles in a cohort of Chinese rhesus macaques (Macaca mulatta). . Hum Immunol 69:, 513–521. [CrossRef][PubMed]
    [Google Scholar]
  26. Schøller J., Singh M., Bergmeier L., Brunstedt K., Wang Y., Whittall T., Rahman D., Pido-Lopez J., Lehner T.. ( 2010;). A recombinant human HLA-class I antigen linked to dextran elicits innate and adaptive immune responses. . J Immunol Methods 360:, 1–9. [CrossRef][PubMed]
    [Google Scholar]
  27. Shearer G. M., Clerici M., Dalgleish A.. ( 1993;). Alloimmunization as an AIDS vaccine?. Science 262:, 161–162. [CrossRef][PubMed]
    [Google Scholar]
  28. Stott E. J.. ( 1991;). Anti-cell antibody in macaques. . Nature 353:, 393. [CrossRef][PubMed]
    [Google Scholar]
  29. Stott E. J., Almond N., West W., Kent K., Cranage M., Rud E.. ( 1994;). Protection against simian immunodeficiency virus infection of macaques by cellular or viral antigens. . In Neuvieme Colloque Cent Gardes, pp. 219–224. Edited by Girard M., Vallette L... Lyon:: Foundation Merieux;.
    [Google Scholar]
  30. Thobakgale C. F., Prendergast A., Crawford H., Mkhwanazi N., Ramduth D., Reddy S., Molina C., Mncube Z., Leslie A.. & other authors ( 2009;). Impact of HLA in mother and child on disease progression of pediatric human immunodeficiency virus type 1 infection. . J Virol 83:, 10234–10244. [CrossRef][PubMed]
    [Google Scholar]
  31. Wang Y., Tao L., Mitchell E., Bravery C., Berlingieri P., Armstrong P., Vaughan R., Underwood J., Lehner T.. ( 1999;). Allo-immunization elicits CD8+ T cell-derived chemokines, HIV suppressor factors and resistance to HIV infection in women. . Nat Med 5:, 1004–1009. [CrossRef][PubMed]
    [Google Scholar]
  32. Wang Y., Underwood J., Vaughan R., Harmer A., Doyle C., Lehner T.. ( 2002;). Allo-immunization elicits CCR5 antibodies, SDF-1 chemokines, and CD8-suppressor factors that inhibit transmission of R5 and X4 HIV-1 in women. . Clin Exp Immunol 129:, 493–501. [CrossRef][PubMed]
    [Google Scholar]
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