Autoreactivity in HIV-infected individuals does not increase during vaccination with envelope rgp160.
The HIV-1 envelope protein contains several regions with amino acid homology to HLA class I and class II molecules. We evaluated possible changes in antibody responses to those regions during vaccination with rgp 160 produced in a baculovirus system. Forty asymptomatic HIV-infected patients with CD4 cell counts above 400 were vaccinated with rgp 160. Twenty-one patients were tissue-typed as HLA A2. Sixty-two percent of these patients exhibited cytotoxic lymphocyte antibodies directed to CD8+, HLA A2 cells. This cytotoxicity decreased during HIV gp160 vaccination. In order to further characterize the specificity of these responses, analogues of HLA class I and HLA-DR peptides were chemically synthesized together with their correct HIV-1 gp160 sequences. Enzyme-linked immunosorbent assays (ELISA) with sera from before, during and after immunization were performed with HIV proteins, peptides and their homologues. All patients showed an increase in their previously poor specific T-cell activation to gp160. Fourteen patients developed increased avidities or titres to HIV proteins and/or peptides. Contrarily, serum IgG titers to the HLA homologous peptides were initially low and decreased further during the course of vaccination. This decrease occurred in the majority of patients, 35-40 of the 40 individuals, depending on the antigen. Independent measures of autoantibodies to Ro/SS-A and La/SS-B remained undetectable.
Lundholm
P
P
Swedish Institute for Infectious Disease Control, Stockholm.
Wahren
M
M
Sandström
E
E
Volvovitz
F
F
Wahren
B
B
D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D016915:AIDS Vaccines; D001323:Autoantibodies; D001324:Autoantigens; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D011498:Protein Precursors; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; D014614:Vaccines, Synthetic; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C116006:RO60 protein, human