| 1. |
- Vinner, Lasse, et al.
(författare)
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Sequence analysis of HIV-1 isolates from Guinea-Bissau: selection of vaccine epitopes relevant in both West African and European countries.
- 2011
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Ingår i: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. - : Wiley. - 1600-0463. ; 119:8, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- For a CD8 epitope-based vaccine to match different geographic locations, the targeted epitopes for cytotoxic T-lymphocytes (CTLs) must be present in the local circulating HIV-1 strains. Secondly, the vaccine epitopes should match the host population HLA types. We characterized two new HIV-1 isolates from Guinea-Bissau. Also, we have identified 15 subdominant CD8 epitopes representing common HLA super-types theoretically covering most HLA alleles in any population. Herein we demonstrate that the selected vaccine epitopes are well conserved and simultaneously present in sequences from West Africa and Denmark. Use of the selected epitopes will likely ensure 10 immune targets in the majority of candidates for experimental therapeutic vaccination in both geographic regions. Our results warrant testing of the selected vaccine epitopes in both geographic locations.
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| 2. |
- Gram, Gregers J., 1968
(författare)
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Immune recognition and early virus-cell interactions. Glycobiological aspects on HIV-1 gp120
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) are the etiological agents of AIDS in humans. The viral envelope glycoproteins gp120 and gp41 mediate the early virus-cell interaction of HIV with the target cells. The envelope glycoprotein is organised into trimeric complexes on the virion surface and the heavily glycosylated gp120 contains both N- and O-linked glycans. The glycosylation is necessary for generation of correct conformation but it is also an important component to decrease the susceptibility of the virus to immune responses of the host. These and other factors are likely to influence the progression of the natural infection in HIV infected individuals. Several aspects of N-linked glycans and O-linked glycans of gp120 were investigated. We characterised two N-glycan in the V1-loop and V3-loop of gp120 and found both N-glycans to be of the complex type. Further, these N-glycans was found to influence the sensitivity of the virus to neutralising antibodies. We deleted all potential O-glycan sites in the V3-loop of gp120, to pin-point the unknown location of broadly O-linked neutralisation epitopes of gp120. However, the location of these neutralisation epitopes must be outside of the V3-loop. Using a novel deglycosylation assay, we identified N-glycans located in the vicinity of the CD4 binding site and epitopes on gp120 recognised by antibodies from HIV infected individuals. However, these recognition sites were found to be only partly overlapping. These antibody responses are likely to influence the progression of infection in HIV infected individuals, but the presence of autologous neutralising antibodies was not a requirement in persons displaying a slow progressing HIV infection. However, a non-syncytium viral phenotype in conjunction with a mutant allele carrying a 32 base pair deletion in the CCR5 co-receptor gene, was found to be predictive for slow progressing infection.
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