Assessment of the Feasibility of a Different HIV Vaccine Approach
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Date
2011Author
Kimani, M
Wachihi, C
Kimani, J
Language
enMetadata
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Background: The failure of Merck STEP and Phambili trials and
the modest effect of RV144 trial emphasize the importance of
understanding the correlates of protective immunity. Our study
showed that the epitope recognition of HLA alleles associated
with protection from HIV-1 infection is very narrow, thus vaccines
focus on the key sites of HIV-1 might work better. Since the
protease cleavage sites of HIV-1 are highly conserved among
major subtypes, direct immune responses against these sites
would yield two major advantages. First, the immune response
could destroy the virus before it can establish permanently in the
host. Second, the vaccine could force the virus to accumulate
mutations eliminating the normal function of the HIV protease
thus eliminating viable virions. For this vaccine strategy to work a
given individual must have a HLA class I allele that can recognize
one of the peptides overlapping one of the 12 protease cleavage
sites of HIV-1. In this study we examined the population coverage
of this vaccine approach using several approaches.
Methods: The population coverage was predicted using computational
algorithms, the Population Coverage Calculator
(http://www.immuneepitope.org/) with the clade A and D
peptides overlapping the protease cleavage sites (PCSs). The
population coverage was also calculated based on the T cell epitopes
that have already been identified at these sites. Furthermore,
the peptides overlapping the 12 PCSs were screened with 8
HLA class I alleles using iTopia Epitope Discovery system and
confirmed using IFNc ELISPOT assays with PBMCs.
Results: Analysis using all three approaches showed that the
percentage of populations in the world can recognize peptides
overlapping at least one PCS is very high, including more than
90% population in Sub-Saharan Africa. iTopia epitope Discovery
System screen showed that the eight common HLA alleles have
epitopes in multiple PCSs (4 to 12).
Conclusion: This vaccine approach has good population
coverage.
Citation
Kimani, M.,Wachihi, C.,Kimani, J.,2011.Assessment of the Feasibility of a Different HIV Vaccine Approach.Publisher
University Of Nairobi
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- Faculty of Health Sciences (FHS) [10385]