A vaccine for HIV type 1: The antibody perspective

Burton, Dennis R.

doi:10.1073/pnas.94.19.10018

Cited by 197 publications

(101 citation statements)

References 70 publications

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“…Conjugation of ISS to protein Ags, including gp120, has previously been shown to improve some aspects of their immunogenicity (12,19,27,28). Therefore, we generated the gp120:ISS conjugate to determine whether ISS conjugation might generate an improved immune response to this relatively poorly immunogenic HIV Ag (29). ISS-containing ODN (7.5 kDa) or ODN containing a mutated, nonstimulatory motif (mODN, 7.5 kDa) were conjugated to gp120 protein (120 kDa) as described in Materials and Methods.…”

Section: Synthesis Of the Gp120:iss Conjugatementioning

confidence: 99%

Immunostimulatory DNA-Based Vaccines Elicit Multifaceted Immune Responses Against HIV at Systemic and Mucosal Sites

Horner¹,

Datta²,

Takabayashi³

et al. 2001

The Journal of Immunology

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Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathogen-associated molecular patterns that are potent stimulators of innate immunity. We tested the ability of ISS to act as an immunostimulatory pathogen-associated molecular pattern in a model HIV vaccine using gp120 envelope protein as the Ag. Mice immunized with gp120 and ISS, or a gp120:ISS conjugate, developed gp120-specific immune responses which included: 1) Ab production; 2) a Th1-biased cytokine response; 3) the secretion of β-chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV; 4) CTL activity; 5) mucosal immune responses; and 6) CD8 T cell responses that were independent of CD4 T cell help. Based on these results, ISS-based immunization holds promise for the development of an effective preventive and therapeutic HIV vaccine.

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Section: Synthesis Of the Gp120:iss Conjugatementioning

confidence: 99%

Immunostimulatory DNA-Based Vaccines Elicit Multifaceted Immune Responses Against HIV at Systemic and Mucosal Sites

Horner¹,

Datta²,

Takabayashi³

et al. 2001

The Journal of Immunology

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“…4 In addition to a high mutational rate of HIV, the weak neutralizing antibody response of HIV gp120 also makes vaccine development problematic. 5 Recently, lectins targeting the glycans of HIV gp120 have become attractive candidates as anti-HIV agents. 6,7 Lectins bound to glycans inhibit the HIV entry process, causing steric hindrance between gp120-receptor interaction and by preventing the conformational changes of gp120.…”

Section: Introductionmentioning

confidence: 99%

Actinohivin: specific amino acid residues essential for anti-HIV activity

et al. 2010

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Actinohivin (AH) is a microbial lectin containing 114 amino acids, which inhibits human immunodeficiency virus (HIV) infection. This effect is brought about by its specific binding to Man-a(1-2)-Man unit(s) of high-mannose type glycan (HMTG) bound to HIV gp120. The recently determined crystal structure of AH suggests that three repeated segments (the residue numbers 1-38, 39-76 and 77-114 for segments 1, 2 and 3, respectively) form three sugar-binding pockets to accommodate Man-a(1-2)-Man units. The strong specific binding of AH to gp120 is considered to be due to multivalent interaction of the three sugar-binding pockets with three HMTGs of gp120 via the 'cluster effect' of lectin. It remains to be seen which residues of the sugar-binding pockets are essential for acceptance of Man-a(1-2)-Man. To identify the amino acid residues critical for anti-HIV effect, we performed mutational analysis. Mutant AHs were subjected to enzyme-linked immunosorbent assay testing for gp120-binding activity and to syncytium formation assay. As a result, it was revealed that Asp15, Tyr23, Leu25, Asn28 and Tyr32 in segment 1, Tyr61 in segment 2 and Tyr99 in segment 3 are essential for anti-HIV activity. The conserved residues, Asp53, Leu63, Asn66 and Tyr70, in segment 2 and, Asp91, Leu101, Asn104 and Tyr108, in segment 3 are also necessary. Furthermore, aromatic residues at positions 23 and 32 are required for creation of potency. These data will be useful for predicting the detailed mechanism of AH-Man-a(1-2)-Man/HMTG/gp120 interaction by computational analysis and for possible development of more potent microbicides for prevention of HIV transmission.

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“…The development of a vaccine active against multiple clades of HIV is complicated by the high mutation rate of the virus (2). In the absence of vaccines, there is a growing interest in the development of anti-HIV virucides for either topical or ex vivo use (3).…”

mentioning

confidence: 99%

Structures of the Complexes of a Potent Anti-HIV Protein Cyanovirin-N and High Mannose Oligosaccharides

Botos

O’Keefe

Shenoy

et al. 2002

Journal of Biological Chemistry

172

201

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The development of anti-human immunodeficiency virus (HIV) microbicides for either topical or ex vivo use is of considerable interest, mainly due to the difficulties in creating a vaccine that would be active against multiple clades of HIV. Cyanovirin-N (CV-N), an 11-kDa protein from the cyanobacterium (blue-green algae) Nostoc ellipsosporum with potent virucidal activity, was identified in the search for such antiviral agents. The binding of CV-N to the heavily glycosylated HIV envelope protein gp120 is carbohydrate-dependent. Since previous CV-N-dimannose structures could not fully explain CV-N-oligomannose binding, we determined the crystal structures of recombinant CV-N complexed to Man-9 and a synthetic hexamannoside, at 2.5-and 2.4-Å resolution, respectively. CV-N is a three-dimensional domainswapped dimer in the crystal structures with two primary sites near the hinge region and two secondary sites on the opposite ends of the dimer. The binding interface is constituted of three stacked ␣132-linked mannose rings for Man-9 and two stacked mannose rings for hexamannoside with the rest of the saccharide molecules pointing to the solution. These structures show unequivocally the binding geometry of high mannose sugars to CV-N, permitting a better understanding of carbohydrate binding to this potential new lead for the design of drugs against AIDS.

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A vaccine for HIV type 1: The antibody perspective

Cited by 197 publications

References 70 publications

Immunostimulatory DNA-Based Vaccines Elicit Multifaceted Immune Responses Against HIV at Systemic and Mucosal Sites

Immunostimulatory DNA-Based Vaccines Elicit Multifaceted Immune Responses Against HIV at Systemic and Mucosal Sites

Actinohivin: specific amino acid residues essential for anti-HIV activity

Structures of the Complexes of a Potent Anti-HIV Protein Cyanovirin-N and High Mannose Oligosaccharides

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