Clade Specific Neutralising Vaccines for HIV: An Appropriate Target?

Aasa-Chapman, Marlén M. I.

doi:10.2174/157016207782418524

Cited by 9 publications

(7 citation statements)

References 77 publications

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“…HIV-1 diversity influences rates of virus transmission 24 and disease progression, 25 highlighting the importance of elucidating cladeassociated properties. This possibly paved the way for evaluating HIV-1 vaccine concepts based on geographic region 26 and global approaches. 10,27 Induction and subsequent detection of virus-induced immune responses are major objectives of HIV vaccine formulations.…”

Section: Discussionmentioning

confidence: 99%

Profile of T Cell Recognition of HIV Type 1 Consensus Group M Gag and Nef Peptides in a Clade A1- and D-Infected Ugandan Population

Serwanga

Mugaba²,

Pimego³

et al. 2012

AIDS Research and Human Retroviruses

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Reagents for evaluating non-clade B HIV-specific T cell responses are uncommon. Peptides based on highly conserved HIV-1 consensus group M sequences that are phylogenetically closer to most circulating strains may provide potential alternative reagents in populations with diverse infections, and may be relevant for vaccine design. Recognition of such reagents in clade A1-and D-infected populations has not been previously evaluated. Interferon (IFN)-γ ELISpot assay was used to evaluate T cell recognition of Gag and Nef peptides based on consensus group M sequences in 50 treatment-naive adults predominantly infected with HIV-1 clades A1 and D. Gag-induced T cell responses were correlated with gag sequence diversity. Infecting clades were determined from gag sequences for 45 of the 50 subjects as 40% clade A1 (18/45), 45% clade D (20/45), 2% clade C (1/45), 2% A1/C recombinant (1/45), 2% A1/D (1/45), 7% CRF10_CD (3/45), and 2% U (unclassifiable) (1/45). The mean genetic divergence and diversity of clade A and D gag region compared to group M consensus sequences at synonymous and nonsynonymous nucleotide and amino acid levels were not always significant. Gag peptides were targeted at significantly higher frequency [88% (44/50)] than Nef [64% (32/50)]; p=0.014, although their mean IFN-γ magnitudes were comparable ([3703 (95% CI 2567-4839)] vs. [2120 (95% CI 478-3762)]), respectively. Measurable virus-induced IFN-γ responses were detected in 96% (48/50) individuals, primarily targeting the more conserved Gag p24 and Nef central core regions. Use of these reagents to screen for HIV-specific IFN-γ responses may mitigate the challenge of viral diversity; although this targeting is apparently biased toward a few highly conserved epitopes.

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Section: Discussionmentioning

confidence: 99%

Profile of T Cell Recognition of HIV Type 1 Consensus Group M Gag and Nef Peptides in a Clade A1- and D-Infected Ugandan Population

Serwanga

Mugaba²,

Pimego³

et al. 2012

AIDS Research and Human Retroviruses

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“…Other studies analyzed the sequence evolution in infected individuals and showed that the C3 region, including the externally accessible residues, is under strong positive selection both in clade B [ 24 - 26 ] and in HIV-1 subtype C infections [ 23 ]. These results may be of particular interest since this antigenic portion of the gp120 molecule has been considered in the development of candidate vaccines [ 52 - 56 ]-.…”

Section: Discussionmentioning

confidence: 99%

Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV-1) gp120 CD4-binding site in a group of long term non progressor (LTNP) subjects

et al. 2009

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The characteristics of intra-host human immunodeficiency virus type 1 (HIV-1) env evolution were evaluated in untreated HIV-1-infected subjects with different patterns of disease progression, including 2 normal progressor [NP], and 5 Long term non-progressor [LTNP] patients. Highresolution phylogenetic analysis of the C2-C5 env gene sequences of the replicating HIV-1 was performed in sequential samples collected over a 3-5 year period; overall, 301 HIV-1 genomic RNA sequences were amplified from plasma samples, cloned, sequenced and analyzed. Firstly, the evolutionary rate was calculated separately in the 3 codon positions. In all LTNPs, the 3 rd codon mutation rate was equal or even lower than that observed at the 1 st and 2 nd positions (p = 0.016), thus suggesting strong ongoing positive selection. A Bayesian approach and a maximum-likelihood (ML) method were used to estimate the rate of virus evolution within each subject and to detect positively selected sites respectively. A great number of N-linked glycosylation sites under positive selection were identified in both NP and LTNP subjects. Viral sequences from 4 of the 5 LTNPs showed extensive positive selective pressure on the CD4-binding site (CD4bs). In addition, localized pressure in the area of the IgG-b12 epitope, a broad neutralizing human monoclonal antibody targeting the CD4bs, was documented in one LTNP subject, using a graphic colour grade 3-dimensional visualization. Overall, the data shown here documenting high selective pressure on the HIV-1 CD4bs of a group of LTNP subjects offers important insights for planning novel strategies for the immune control of HIV-1 infection.

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“…One of the major obstacles to the development of an efficacious antibody response is the extraordinary diversity of HIV Envelope (Env) (45,46), the surface glycoprotein that is the target of neutralizing antibodies (70,84). The structural features of HIV Env, such as flexible loops and extensive glycosylation, also provide resistance to neutralization (reviewed in reference 62).…”

Section: % Of B Cells and 0047% Of Plasmablasts Secreted Env-spementioning

confidence: 99%

Frequency and Phenotype of Human Immunodeficiency Virus Envelope-Specific B Cells from Patients with Broadly Cross-Neutralizing Antibodies

Doria‐Rose¹,

Klein²,

Manion³

et al. 2009

J Virol

289

243

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Induction of broadly cross-reactive neutralizing antibodies (NAb) is an important goal for a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine. Some HIV-infected patients make a NAb response that reacts with diverse strains of HIV-1, but most candidate vaccines have induced NAb only against a subset of highly sensitive isolates. To better understand the nature of broad NAb responses that arise during natural infection, we screened patients for sera able to neutralize diverse HIV strains and explored the frequency and phenotype of their peripheral Envelope-specific B cells. We screened 113 HIV-infected patients of various clinical statuses for the prevalence of broad NAb. Sera able to neutralize at least four of five viral isolates were found in over one-third of progressors and slow progressors, but much less frequently in aviremic long-term nonprogressors. Most Env-specific antibody-secreting B cells were CD27 hi CD38 hi plasmablasts, and the total plasmablast frequency was higher in HIV-infected patients than in uninfected donors. We found that 0.0031% of B cells and 0.047% of plasmablasts secreted Env-specific immunoglobulin G (IgG) in an enzyme-linked immunospot (ELISPOT) assay. We developed a novel staining protocol to label HIV-specific B cells with Env gp140 protein. A total of 0.09% of B cells were found to be Env-specific by this method, a frequency far higher than that indicated by ELISPOT assay. gp140-labeled B cells were predominantly CD27 ؉ and surface IgG ؉ . These data describe the breadth and titer of serum NAb and the frequency and phenotype of HIV-specific B cells in a cohort of patients with broad cross-neutralizing antibody responses that are potential goals for vaccines for HIV.

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Clade Specific Neutralising Vaccines for HIV: An Appropriate Target?

Cited by 9 publications

References 77 publications

Profile of T Cell Recognition of HIV Type 1 Consensus Group M Gag and Nef Peptides in a Clade A1- and D-Infected Ugandan Population

Profile of T Cell Recognition of HIV Type 1 Consensus Group M Gag and Nef Peptides in a Clade A1- and D-Infected Ugandan Population

Dynamic features of the selective pressure on the human immunodeficiency virus type 1 (HIV-1) gp120 CD4-binding site in a group of long term non progressor (LTNP) subjects

Frequency and Phenotype of Human Immunodeficiency Virus Envelope-Specific B Cells from Patients with Broadly Cross-Neutralizing Antibodies

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