title: Immunization with recombinant HLA classes I and II, HIV-1 gp140, and SIV p27 elicits protection against heterologous SHIV infection in rhesus macaques.
abstract: Major histocompatibility complex (MHC) molecules expressed on the surface of human immunodeficiency virus (HIV) are potential targets for neutralizing antibodies. Since MHC molecules are polymorphic, nonself MHC can also be immunogenic. We have used combinations of novel recombinant HLA class I and II and HIV/simian immunodeficiency virus (SIV) antigens, all linked to dextran, to investigate whether they can elicit protective immunity against heterologous simian/human immunodeficiency virus (SHIV) challenge in rhesus macaques. Three groups of animals were immunized with HLA (group 1, n = 8), trimeric YU2 HIV type 1 (HIV-1) gp140 and SIV p27 (HIV/SIV antigens; group 2, n = 8), or HLA plus HIV/SIV antigens (group 3, n = 8), all with Hsp70 and TiterMax Gold adjuvant. Another group (group 4, n = 6) received the same vaccine as group 3 without TiterMax Gold. Two of eight macaques in group 3 were completely protected against intravenous challenge with 18 50% animal infective doses (AID(50)) of SHIV-SF162P4/C grown in human cells expressing HLA class I and II lineages represented in the vaccine, while the remaining six macaques showed decreased viral loads compared to those in unimmunized animals. Complement-dependent neutralizing activity in serum and high levels of anti-HLA antibodies were elicited in groups 1 and 3, and both were inversely correlated with the plasma viral load at 2 weeks postchallenge. Antibody-mediated protection was strongly supported by the fact that transfer of pooled serum from the two challenged but uninfected animals protected two naïve animals against repeated low-dose challenge with the same SHIV stock. This study demonstrates that immunization with recombinant HLA in combination with HIV-1 antigens might be developed into an alternative strategy for a future AIDS vaccine.
authors.affiliation: Vaccinology Unit, Swedish Institute for Communicable Disease Control, S-171 82 Solna, Sweden. andreas.morner@smi.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Mörner
authors.forename: Marianne
authors.initials: M
authors.lastname: Jansson
authors.forename: Evelien M
authors.initials: EM
authors.lastname: Bunnik
authors.forename: Jørgen
authors.initials: J
authors.lastname: Schøller
authors.forename: Robert
authors.initials: R
authors.lastname: Vaughan
authors.forename: Yufei
authors.initials: Y
authors.lastname: Wang
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Nel
authors.initials: N
authors.lastname: Otting
authors.forename: Ronald
authors.initials: R
authors.lastname: Bontrop
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Bergmeier
authors.forename: Mahavir
authors.initials: M
authors.lastname: Singh
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wyatt
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Gunnel
authors.initials: G
authors.lastname: Biberfeld
authors.forename: Rigmor
authors.initials: R
authors.lastname: Thorstensson
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehner
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D015395:Histocompatibility Antigens Class I / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D008253:Macaca mulatta / Q000276:immunology; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D018449:SAIDS Vaccines / Q000008:administration & dosage; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D016896:Treatment Outcome; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018449:SAIDS Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1