Immunogenicity Of Sequences Around Hiv-1 Protease Cleavage Sites: Potential Targets And Population Coverage Analysis For A Hiv Vaccine Targeting Protease Cleavage Sites.
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Date
2013-06Author
Luo, M
Capina, R
Daniuk, C
Tuff, J
Peters, H
Kimani, M
Wachihi, C
Kimani, J
Ball, T B
Plummer, F A.
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
Developing an effective preventative vaccine against HIV-1 has proved to be a great challenge. The classical and proven vaccine approach has failed so far or produced a modest effect, new approaches are needed. In this study we evaluated the immunogenicity of the sequences around the protease cleavage sites (PCS) and the population coverage of a vaccine targeting HIV-1 PCS. The sequence conservation was evaluated by comparing entropy score of sequences around PCS with Gag and Pol. The immunogenicity of sequences around the 12 PCS (+10/-10 amino acids) was analyzed by identifying epitopes of HLA class I alleles in PCS region using four approaches: (1) identification of previously reported HLA class I allele epitopes around PCS region; (2) screening and validating epitopes of 8 HLA class I alleles common to most world populations using iTopia Epitope Discovery system and IFN-γ ELISpot assays; (3) screening of 151 patients of Pumwani cohort for PBMC IFN-γ ELISPOT responses to the subtype A and D consensus around PCS region; and (4) prediction of HLA alleles with epitopes around the PCS using NetMHCpan. Population coverage was calculated using the web-based analysis tool of the Immune Epitope Database based on HLA class I genotype frequencies from dbMHC database. The results showed that many HLA class I alleles have multiple epitopes in the 12 PCS regions, indicating sequence immunogenicity around PCS. Multiple epitopes of many HLA class I alleles common to >95% world populations have been identified around the 12 PCS region. Targeting these sites is a feasible vaccine approach.
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http://hinari-gw.who.int/whalecomwww.ncbi.nlm.nih.gov/whalecom0/pubmed/23664989http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/41270
Citation
Vaccine. 2013 Jun 24;31(29):3000-8. doi: 10.1016/j.vaccine.2013.04.057. Epub 2013 May 10.Publisher
University of Nairobi Department of Medical Microbiology
Collections
- Faculty of Health Sciences (FHS) [10378]