Immunological cross-reactivity against a drug mutated HIV-1 protease epitope after DNA multi-CTL epitope construct immunization.
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.
Boberg
Andreas
A
Swedish Institute for Infectious Disease Control, Karolinska Institute, 171 82 Solna, Sweden. andreas.boberg@smi.ki.se
Sjöstrand
Dan
D
Rollman
Erik
E
Hinkula
Jorma
J
Zuber
Bartek
B
Wahren
Britta
B
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*
D000939:Epitopes; D015699:HIV Envelope Protein gp120; D006680:HLA Antigens; D012333:RNA, Messenger; D016333:HIV Protease