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Becker, Y. (1990). "Computer
analysis of antigenic domains and RGD-like sequences
(RGWG) in the E glycoprotein of flaviviruses: an approach
to vaccine development." Virus Genes 4: 267-282.
Antigenic domains and RGD-like sequences in the E glycoprotein
of the flaviviruses Japanese encephalitis virus, yellow
fever virus, West Nile virus, dengue type 4 virus, and
tick-borne encephalitis virus were analyzed by computer
programs that provide information on the physical properties
of the polypeptides. The use of computer programs for
the development of vaccines based on the synthesis of
antigenic peptides is discussed. Synthetic viral peptides
are proposed to be used for topical application so as
to interfere with the virus-cell interaction. Viral
peptides with antigenic epitopes to protect against
dengue virus infection without enhancing pathogenesis
may also be developed on the basis of the computer analysis.
Becker, Y. (1994). "Dengue fever
virus and Japanese encephalitis virus synthetic peptides,
with motifs to fit HLA class I haplotypes prevalent
in human populations in endemic regions, can be used
for application to skin Langerhans cells to prime antiviral
CD8(+) cytotoxic T cells (CTLs) - A novel approach to
the protection of humans." Virus Genes 9: 33-45.
Y Becker, Hebrew Univ Jerusalem, Fac Med, Dept Molec
Virol, IL- 91010 Jerusalem, Israel Flaviviruses were
reported to induce CD8(+) cytotoxic T cells in infected
individuals, indicating that nonapeptides, proteolytic
cleavage products of the viral precursor protein, enter
the endoplasmic reticulum in infected cells and interact
with HLA class I molecules. The assembled KLA class
I molecules are transported to the plasma membrane and
prime CD8(+) T cells. Current knowledge of the interaction
of viral peptides with HLA molecules is reviewed. Based
on this review, an idea is presented to use synthetic
flavivirus peptides with an amino acid motif to fit
with the HLA class I peptide binding group of HLA haplotypes
prevalent in a given population in an endemic area.
These synthetic viral peptides may be introduced into
the human skin using a lotion containing the peptides
(''Peplotion'') together with substances capable of
enhancing the penetration of these peptides into the
skin to reach Langerhans cells. The peptide- treated
Langerhans cells, professional antigen-presenting cells,
may bind the synthetic viral peptides by their HLA class
I peptide-binding grooves. Antigens carrying Langerhans
cells are able to migrate and induce the cellular immune
response in the lymph nodes. This approach to the priming
of antiviral CD8(+) cytotoxic T cells may provide cellular
immune protection from flavivirus infection without
inducing the humoral immune response, which can lead
to the shock syndrome in Dengue fever patients. To be
able to develop anti-Dengue virus synthetic peptides
for populations with different HLA class I haplotypes,
it is necessary to develop computational studies to
design HLA class I Dengue virus synthetic peptides with
motifs to fit the HLA haplotypes of the population living
in an endemic region for Dengue fever. Experiments to
study Dengue virus and Japanese encephalitis peptides
vaccines and their effectiveness in protection against
Dengue fever and Japanese encephalitis are needed. The
development of human antiviral vaccines for application
of viral peptides in a lotion to human skin (''Peplotion'')
may be useful and affordable for populations of developing
countries
 
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