Conserved Neutralizing Epitopes of HIV Type 1 CRF01_AE against Primary Isolates in Long-Term Nonprogressors

Sreepian, Apichai; Srisurapanon, Surangrat; Horthongkham, Nawin; Tunsupasawasdikul, Somsith; Kaoriangudom, Surapol; Khusmith, Srisin; Sutthent, Ruengpung

doi:10.1089/088922204323087787

Cited by 11 publications

(13 citation statements)

References 30 publications

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“…Together with the fact that the C1 region is known to be less variable [43], the C1 epitopes are interesting targets for neutralizing antibodies. Previously, a report by Sreepian et al , described the presence of antibodies against the C1 region in a subtype CRF01_AE infected HIV-1 individual, however, immunization studies performed with C1 epitopes did not result in neutralizing antibodies [44,45]. The role of the C1 antibodies in the neutralization capacity of ITM4 should be further analyzed.…”

Section: Discussionmentioning

confidence: 99%

Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies

et al. 2009

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BackgroundA minority of HIV-1 infected individuals develop broad cross-neutralizing (BCN) plasma antibodies that are capable of neutralizing a spectrum of virus variants belonging to different HIV-1 clades. The aim of this study was to identify the targeted epitopes of an individual with BCN plasma antibodies, referred to as ITM4, using peptide phage display. This study also aimed to use the selected mimotopes as tools to unravel the evolution of the antibody landscape and the viral envelope escape which may provide us with new insights for vaccine design.ResultsThis study led us to identify ITM4 plasma antibodies directed to the 4E10 epitope located in the gp41 membrane-proximal external region (MPER). Analysis of antibody specificities revealed unusual immunogenic properties of the ITM4 viral envelope, as not only the V3 loop and the gp41 MPER but also the C1 and lentivirus lytic peptide 2 (LLP2) region seem to be targets of the immune system. The 4E10-like antibodies are consistently elicited during the 6-year follow up period. HIV-1 ITM4 pseudoviruses showed an increasing resistance over time to MPER monoclonal antibodies 4E10 and 2F5, although no changes are found in the critical positions of the epitope. Neutralization of COT6.15 (subtype C; 4E10-sensitive) pseudoviruses with alanine substitutions in the MPER region indicated an overlapping specificity of the 4E10 monoclonal antibody and the ITM4 follow up plasma. Moreover the 4E10-like antibodies of ITM4 contribute to the BCN capacity of the plasma.ConclusionsUsing ITM4 BCN plasma and peptide phage display technology, we have identified a patient with 4E10-like BCN antibodies. Our results indicate that the elicited 4E10-like antibodies play a role in virus neutralization. The viral RNA was isolated at different time points and the ITM4 envelope sequence analysis of both early (4E10-sensitive) and late (4E10-resistant) viruses suggest that other regions in the envelope, outside the MPER region, contribute to the accessibility and sensitivity of the 4E10 epitope. Including ITM4 specific HIV-1 Env properties in vaccine strategies may be a promising approach.

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Section: Discussionmentioning

confidence: 99%

Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies

et al. 2009

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“…The designation of peptides corresponding C1 (C1E1 and C1E2) and C2 regions (C2E) has been described previously [ 18 ]. The peptides were designed from alignment of env nucleotide sequences (C2-V4) obtained from 43 HIV-1 CRF01_AE primary isolates (GenBank under accession number AF373037 - AF373043 , AY005164 - AY005179 and AF322195 - AF322214 ) [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

“…CRF01_AE, a hybrid of subtype A ( gag ) and E ( env ), is an important HIV-1 recombinant form prevalent in Asia. Since we demonstrated some conserved neutralizable epitopes, which are located on amino acids 93-112 (C1 region) and 218-239 (C2 region) of HIV-1 CRF01_AE primary isolates in previous study [ 18 ], we have attempted to test the immunogenicity of these conserved epitopes and potencies of these induced MAbs. Toward that aim, we immunized BALB/c mice with peptides corresponding to these epitopes and MAbs specific to these epitopes were produced.…”

Section: Introductionmentioning

confidence: 99%

HIV-1 neutralization by monoclonal antibody against conserved region 2 and patterns of epitope exposure on the surface of native viruses

Sreepian

Permmongkol

Kantakamalakul

et al. 2009

J Immune Based Ther Vaccines

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Background: Conserved neutralizing epitopes are considered to be a key role for eliciting broadly neutralizing antibody (NAb). Previously, two conserved neutralizing epitopes of HIV-1 CRF01_AE envelope were identified at amino acid 93-112 of the C1 (C1E) and at 218-239 of the C2 (C2E) regions. To access the potency of antibody directed against conserved epitopes, a monoclonal antibody (MAb) specific to the C2E region was developed and characterized.

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“…First, conserved T-and B-cell epitopes were explored, and many cross-subtype T-cell responses have been identified. 9,15,17,18,43 Although T-cell epitopes are more easily defined than B ¼ cell epitopes, several cross-subtype neutralizing antibodies have been identified and mapped. 7,10,35,44,[48][49][50] However, further experiments have failed to induce antibody responses to these epitopes, and passive transfer is not a practical prophylactic.…”

Section: Introductionmentioning

confidence: 99%

Similar T-Cell Immune Responses Induced by Group M Consensus Env Immunogens with Wild-Type or Minimum Consensus Variable Regions

Weaver

Camacho

Gao

2010

AIDS Research and Human Retroviruses

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Consensus HIV-1 genes can decrease the genetic distances between candidate immunogens and field virus strains. To ensure the functionality and optimal presentation of immunologic epitopes, we generated two group-M consensus env genes that contain variable regions either from a wild-type B/C recombinant virus isolate (CON6) or minimal consensus elements (CON-S) in the V1, V2, V4, and V5 regions. C57BL/6 and BALB/c mice were primed twice with CON6, CON-S, and subtype control (92UG37_A and HXB2/Bal_B) DNA and boosted with recombinant vaccinia virus (rVV). Mean antibody titers against 92UG37_A, 89.6_B, 96ZM651_C, CON6, and CON-S Env protein were determined. Both CON6 and CON-S induced higher mean antibody titers against several of the proteins, as compared with the subtype controls. However, no significant differences were found in mean antibody titers in animals immunized with CON6 or CON-S. Cellular immune responses were measured by using five complete Env overlapping peptide sets: subtype A (92UG37_A), subtype B (MN_B, 89.6_B and SF162_B), and subtype C (Chn19_C). The intensity of the induced cellular responses was measured by using pooled Env peptides; T-cell epitopes were identified by using matrix peptide pools and individual peptides. No significant differences in T-cell immune-response intensities were noted between CON6 and CON-S immunized BALB/c and C57BL/6 mice. In BALB/c mice, 10 and eight nonoverlapping T-cell epitopes were identified in CON6 and CON-S, whereas eight epitopes were identified in 92UG37_A and HXB2/BAL_B. In C57BL/6 mice, nine and six nonoverlapping T-cell epitopes were identified after immunization with CON6 and CON-S, respectively, whereas only four and three were identified in 92UG37_A and HXB2/BAL_B, respectively. When combined together from both mouse strains, 18 epitopes were identified. The group M artificial consensus env genes, CON6 and CON-S, were equally immunogenic in breadth and intensity for inducing humoral and cellular immune responses.

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Conserved Neutralizing Epitopes of HIV Type 1 CRF01_AE against Primary Isolates in Long-Term Nonprogressors

Cited by 11 publications

References 30 publications

Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies

Evolution of antibody landscape and viral envelope escape in an HIV-1 CRF02_AG infected patient with 4E10-like antibodies

HIV-1 neutralization by monoclonal antibody against conserved region 2 and patterns of epitope exposure on the surface of native viruses

Similar T-Cell Immune Responses Induced by Group M Consensus Env Immunogens with Wild-Type or Minimum Consensus Variable Regions

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