title: Immunization with recombinant macaque major histocompatibility complex class I and II and human immunodeficiency virus gp140 inhibits simian-human immunodeficiency virus infection in macaques.
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.
authors.affiliation: State Key Laboratory for Infectious Disease Control and Prevention, National Center for AIDS/STD Control and Prevention, Beijing, PR China.
authors.forename: Gui-Bo
authors.initials: GB
authors.lastname: Yang
authors.affiliation: Kings College London, Guy's Hospital, London, UK.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Kings College London, Guy's Hospital, London, UK.
authors.forename: Kaboutar
authors.initials: K
authors.lastname: Babaahmady
authors.affiliation: Immudex, Copenhagen, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Schøller
authors.affiliation: Kings College London, Guy's Hospital, London, UK.
authors.forename: Durdana
authors.initials: D
authors.lastname: Rahman
authors.affiliation: AMC Medical Research, Amsterdam, The Netherlands.
authors.forename: Evelien
authors.initials: E
authors.lastname: Bunnik
authors.affiliation: Lionex GmbH and Helmholtz Center for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Spallek
authors.affiliation: State Key Laboratory for Infectious Disease Control and Prevention, National Center for AIDS/STD Control and Prevention, Beijing, PR China.
authors.forename: Chun-Miao
authors.initials: CM
authors.lastname: Zong
authors.affiliation: State Key Laboratory for Infectious Disease Control and Prevention, National Center for AIDS/STD Control and Prevention, Beijing, PR China.
authors.forename: Jia-Zhong
authors.initials: JZ
authors.lastname: Duan
authors.affiliation: Institute of Laboratory Animal Sciences of Chinese Academy of Medical Science, Beijing, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Institute of Laboratory Animal Sciences of Chinese Academy of Medical Science, Beijing, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Lionex GmbH and Helmholtz Center for Infection Research, 38124 Braunschweig, Germany.
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.affiliation: Kings College London, Guy's Hospital, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Vaughan
authors.affiliation: Barts and The London Queen Mary's School of Medicine & Dentistry, London, UK.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Bergmeier
authors.affiliation: AMC Medical Research, Amsterdam, The Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.affiliation: State Key Laboratory for Infectious Disease Control and Prevention, National Center for AIDS/STD Control and Prevention, Beijing, PR China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Kings College London, Guy's Hospital, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehner
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007279:Injections, Subcutaneous; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018449:SAIDS Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1