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Recent strategies targeting HIV glycans in vaccine design.

ABSTRACT: Although efforts to develop a vaccine against HIV have so far met with little success, recent studies of HIV-positive patients with strongly neutralizing sera have shown that the human immune system is capable of producing potent and broadly neutralizing antibodies (bnAbs), some of which neutralize up to 90% of HIV strains. These antibodies bind conserved vulnerable sites on the viral envelope glycoprotein gp120, and identification of these sites has provided exciting clues about the design of potentially effective vaccines. Carbohydrates have a key role in this field, as a large fraction of bnAbs bind carbohydrates or combinations of carbohydrate and peptide elements on gp120. Additionally, carbohydrates partially mask some peptide surfaces recognized by bnAbs. The use of engineered glycoproteins and other glycostructures as vaccines to elicit antibodies with broad neutralizing activity is therefore a key area of interest in HIV vaccine design.

SUBMITTER: Horiya S

PROVIDER: S-EPMC4431543 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Recent strategies targeting HIV glycans in vaccine design.

Horiya Satoru S MacPherson Iain S IS Krauss Isaac J IJ

Nature chemical biology 20141201 12

Although efforts to develop a vaccine against HIV have so far met with little success, recent studies of HIV-positive patients with strongly neutralizing sera have shown that the human immune system is capable of producing potent and broadly neutralizing antibodies (bnAbs), some of which neutralize up to 90% of HIV strains. These antibodies bind conserved vulnerable sites on the viral envelope glycoprotein gp120, and identification of these sites has provided exciting clues about the design of p ...[more]

PMID: 25393493

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Project description:A successful HIV vaccine will likely induce both humoral and cell-mediated immunity, however, the enormous diversity of HIV has hampered the development of a vaccine that effectively elicits both arms of the adaptive immune response. To tackle the problem of viral diversity, T cell-based vaccine approaches have focused on two main strategies (i) increasing the breadth of vaccine-induced responses or (ii) increasing vaccine-induced responses targeting only conserved regions of the virus. The relative extent to which set-point viremia is impacted by epitope-conservation of CD8(+) T cell responses elicited during early HIV-infection is unknown but has important implications for vaccine design. To address this question, we comprehensively mapped HIV-1 CD8(+) T cell epitope-specificities in 23 ART-naïve individuals during early infection and computed their conservation score (CS) by three different methods (prevalence, entropy and conseq) on clade-B and group-M sequence alignments. The majority of CD8(+) T cell responses were directed against variable epitopes (p<0.01). Interestingly, increasing breadth of CD8(+) T cell responses specifically recognizing conserved epitopes was associated with lower set-point viremia (r?=?- 0.65, p?=?0.009). Moreover, subjects possessing CD8(+) T cells recognizing at least one conserved epitope had 1.4 log10 lower set-point viremia compared to those recognizing only variable epitopes (p?=?0.021). The association between viral control and the breadth of conserved CD8(+) T cell responses may be influenced by the method of CS definition and sequences used to determine conservation levels. Strikingly, targeting variable versus conserved epitopes was independent of HLA type (p?=?0.215). The associations with viral control were independent of functional avidity of CD8(+) T cell responses elicited during early infection. Taken together, these data suggest that the next-generation of T-cell based HIV-1 vaccines should focus on strategies that can elicit CD8(+) T cell responses to multiple conserved epitopes of HIV-1.

Dataset Information

Recent strategies targeting HIV glycans in vaccine design.

Publications

Recent strategies targeting HIV glycans in vaccine design.

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