Immunization with recombinant macaque major histocompatibility complex class I and II and human immunodeficiency virus gp140 inhibits simian–human immunodeficiency virus infection in macaques
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.
BabaahmadyK., OehlmannW., SinghM., LehnerT.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 [View Article][PubMed]
BogersW. M., BergmeierL. A., MaJ., OostermeijerH., WangY., KellyC. G., Ten HaaftP., SinghM., HeeneyJ. L., LehnerT.2004; A novel HIV-CCR5 receptor vaccine strategy in the control of mucosal SIV/HIV infection. AIDS 18:25–36 [View Article][PubMed]
GilbertP., WangM., WrinT., PetropoulosC., GurwithM., SinangilF., D’SouzaP., Rodriguez-ChavezI. R., DeCampA.other authors2010; 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 [View Article][PubMed]
GoulderP. J., WatkinsD. I.2008; Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol 8:619–630 [View Article][PubMed]
International HIV Controllers Study2010; The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330:1551–1557 [View Article][PubMed]
KingsleyC., PetersB., BabaahmadyK., PomeroyL., RahmanD., VaughanR., LehnerT.2009; Heterosexual and homosexual partners practising unprotected sex may develop allogeneic immunity and to a lesser extent tolerance. PLoS ONE 4:e7938 [View Article][PubMed]
LangloisA. J., WeinholdK. J., MatthewsT. J., GreenbergM. L., BolognesiD. P.1992; The ability of certain SIV vaccines to provoke reactions against normal cells. Science 255:292–293 [View Article][PubMed]
LehnerT., ShearerG. M., HackettC. J., SchultzA., SharmaO. K.2000; Alloimmunization as a strategy for vaccine design against HIV/AIDS. AIDS Res Hum Retroviruses 16:309–313 [View Article][PubMed]
LeithJ. G., ClarkD. A., MatthewsT. J., RosenthalK. L., LuscherM. A., BarberB. H., MacDonaldK. S.2003; Assessing human alloimmunization as a strategy for inducing HIV type 1 neutralizing anti-HLA responses. AIDS Res Hum Retroviruses 19:957–965 [View Article][PubMed]
MitchellE. A., BergmeierL. A., DoyleC., BrookesR., HussainL. A., WangY., LehnerT.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 [View Article][PubMed]
MörnerA., JanssonM., BunnikE. M., SchøllerJ., VaughanR., WangY., MontefioriD. C., OttingN., BontropR.other authors2011; 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 [View Article][PubMed]
OttingN., MörnerA., BontropR. E.2011; Novel major histocompatibility complex class I alleles extracted from two rhesus macaque populations. Tissue Antigens 77:79–80 [View Article][PubMed]
PolyanskayaN., SharpeS., CookN., LeechS., BanksJ., DennisM., HallG., StottJ., CranageM.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 [View Article][PubMed]
QiuC.-L., YangG.-B., YuK., LiY., LiX.-L., LiuQ., ZhaoH., XingH., ShaoY.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 [View Article][PubMed]
StottE. J., AlmondN., WestW., KentK., CranageM., RudE.1994; Protection against simian immunodeficiency virus infection of macaques by cellular or viral antigens. In Neuvieme Colloque Cent Gardes pp. 219–224 Edited by GirardM., ValletteL. Lyon: Foundation Merieux;
ThobakgaleC. F., PrendergastA., CrawfordH., MkhwanaziN., RamduthD., ReddyS., MolinaC., MncubeZ., LeslieA.other authors2009; Impact of HLA in mother and child on disease progression of pediatric human immunodeficiency virus type 1 infection. J Virol 83:10234–10244 [View Article][PubMed]
WangY., TaoL., MitchellE., BraveryC., BerlingieriP., ArmstrongP., VaughanR., UnderwoodJ., LehnerT.1999; Allo-immunization elicits CD8+ T cell-derived chemokines, HIV suppressor factors and resistance to HIV infection in women. Nat Med 5:1004–1009 [View Article][PubMed]
Immunization with recombinant macaque major histocompatibility complex class I and II and human immunodeficiency virus gp140 inhibits simian–human immunodeficiency virus infection in macaques