title: Immunological cross-reactivity against a drug mutated HIV-1 protease epitope after DNA multi-CTL epitope construct immunization.
abstract: Epitopes in HIV polymerase were analyzed by peptide binding to human leukocyte antigen (HLA) A0201 molecules, the most frequent HLA class in the Caucasian population. We found that HIV-1 protease peptides representing both the wild type and anticipated drug resistance variants of the sequence bound well to HLA-A0201. We also found that wild type as well as a double mutated variant of the epitope was strongly immunogenic in HLA-A0201 transgenic mice, either as individual peptides or encoded in DNA multi-CTL epitope constructs. Immunological cross-reactivity between different variants of the peptide could be seen, suggesting that it may be possible to induce a broad immune response by immunizing with drug resistance-mutated epitopes. This may be of advantage for HIV-1 infected patients since such a response may cause a better outcome of an anti-retroviral drug therapy.
authors.affiliation: Swedish Institute for Infectious Disease Control, Karolinska Institute, 171 82 Solna, Sweden. andreas.boberg@smi.ki.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Boberg
authors.forename: Dan
authors.initials: D
authors.lastname: Sjöstrand
authors.forename: Erik
authors.initials: E
authors.lastname: Rollman
authors.forename: Jorma
authors.initials: J
authors.lastname: Hinkula
authors.forename: Bartek
authors.initials: B
authors.lastname: Zuber
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D016333:HIV Protease / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000939:Epitopes; D015699:HIV Envelope Protein gp120; D006680:HLA Antigens; D012333:RNA, Messenger; D016333:HIV Protease