Sirvi Autor "Adojaan, Maarja" järgi

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Molecular variation of HIV-1 and the use of this knowledge in vaccine development
(2009-11-13T08:59:15Z) Adojaan, Maarja
We characterized HIV-1 genetic diversity in Estonian population since the beginning of the epidemic in year 2000. Phylogenetic analysis revealed that a rare circulating recombinant form CRF06_cpx was predominant. Additionally, high incidence of different unique recombinant forms was detected, consisting of stretches of subtypes A and CRF06_cpx. A new CRF, namely CRF32_06A1 was designated. We also studied HIV-1 co-receptor CCR5 polymorphism among Estonian HIV-1 patients. We found that CCR5Δ32 heterozygosity occurs with the same frequency among HIV-1 seropositives as in healthy control population, suggesting that CCR5Δ32 heterozygosity does not confer protection from HIV-1 infection. CCR5Δ32 allele frequencies among sexually infected patients versus intravenous drug users did not reveal statistically significant differences. No association between CCR5Δ32 genotype status and frequency of dual infection was found. MultiHIV antigens were designed by fusing regulatory early viral proteins Rev, Nef, and Tat; structural proteins Gag p17 and Gag p24, as well as human T cell epitope-rich regions from protease, reverse transcriptase, and envelope proteins Envgp120 and Envgp41. We showed a successful induction of broad cellular anti-HIV immune response with a MultiHIV-B consensus antigen and demonstrated that the CTL response was directed against all constituents of the MultiHIV antigen in domestic pig. All immunized study animals were SLA-I- genotyped to assess the genome diversity of the SLA class I loci. SLA typing revealed considerably high heterogeneity: all swine had a unique SLA class I allelic combination. We demonstrated that pig is an excellent test animal for studying T cell responses in immunological surveys, e.g. in vaccine evaluation studies.