Exclusion of HIV epitopes shared with human proteins is prerequisite for designing safer AIDS vaccines.
BACKGROUND
The safety of a potential AIDS vaccine is an issue that will become critical at later stages of product development and needs to be addressed before it is too late.


OBJECTIVE
In order to design safer vaccine, the HIV antigens, to be deployed in it, should be free of regions that are either present in human proteins or exhibit pronounced structural similarity to proteins responsible for important physiological functions.


METHODS
The approach is based on the use of an original matrix predicting the antigenic similarity of amino acids. This mathematical approach developed by us was applied for identification of fragments with similarity to human proteins within potentially immunodominant regions of HIV proteins. A potential self-sensitization by viral quasispecies with variants of hypervariable V3 region, generated as a result of immune pressure on the immunodominant region of envelope, was considered in detail.


RESULTS
Viral fragments occurring in normal human proteins as well as regions exhibiting high similarity to proteins responsible for physiological homeostasis were identified in every HIV protein at a frequency higher than expected. Most such regions contained either T-cell (CD8(+) CTL or CD4(+) Helper) or B-cell epitopes, or both of them simultaneously. The gained knowledge was applied in designing a synthetic immunogen containing multiple CTL epitopes. The synthesis of series of chimeric peptides representing hypervariable region of V3 loop of HIV envelope, to be used as a multi-epitope or mixotope vaccine candidate, has been achieved. Such a vaccine could theoretically pre-empt any escape mutant borrowing from antigenic diversity of hypervariable region of V3 loop of HIV envelope.


CONCLUSIONS
The epitopes shared by HIV and its host are likely to be implicated in the immunopathogenesis of AIDS through induction of cross-reacting effectors of the immune system. The prospect that 'house-keeping' immune mechanism can be foiled by molecular mimicry of HIV with physiologically important human proteins should be taken into consideration in safer vaccine design.
Maksyutov
Amir Z
AZ
State Research Center of Virology and Biotechnology VECTOR, Koltsovo, Novosibirsk Region 630559, Russia. maksyutov@vector.nsc.ru
Bachinskii
Alexander G
AG
Bazhan
Sergei I
SI
Ryzhikov
Evgenii A
EA
Maksyutov
Zaki A
ZA
D016915:AIDS Vaccines; D000465:Algorithms; D000595:Amino Acid Sequence; D000596:Amino Acids; D000939:Epitopes / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008954:Models, Biological; D012191:Retroviridae Proteins / Q000737:chemistry* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D000596:Amino Acids; D000939:Epitopes; D012191:Retroviridae Proteins; D014614:Vaccines, Synthetic