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1.
Immunity ; 51(1): 141-154.e6, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315032

RESUMO

The VH1-2 restricted VRC01-class of antibodies targeting the HIV envelope CD4 binding site are a major focus of HIV vaccine strategies. However, a detailed analysis of VRC01-class antibody development has been limited by the rare nature of these responses during natural infection and the lack of longitudinal sampling of such responses. To inform vaccine strategies, we mapped the development of a VRC01-class antibody lineage (PCIN63) in the subtype C infected IAVI Protocol C neutralizer PC063. PCIN63 monoclonal antibodies had the hallmark VRC01-class features and demonstrated neutralization breadth similar to the prototype VRC01 antibody, but were 2- to 3-fold less mutated. Maturation occurred rapidly within ∼24 months of emergence of the lineage and somatic hypermutations accumulated at key contact residues. This longitudinal study of broadly neutralizing VRC01-class antibody lineage reveals early binding to the N276-glycan during affinity maturation, which may have implications for vaccine design.


Assuntos
Vacinas contra a AIDS/imunologia , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/metabolismo , Anticorpos Amplamente Neutralizantes/metabolismo , Anticorpos Anti-HIV/metabolismo , Infecções por HIV/imunologia , HIV-1/fisiologia , Vacinas contra a AIDS/genética , Sequência de Aminoácidos , Anticorpos Monoclonais/genética , Anticorpos Neutralizantes/genética , Afinidade de Anticorpos , Linfócitos B/imunologia , Anticorpos Amplamente Neutralizantes/genética , Antígenos CD4/metabolismo , Regiões Determinantes de Complementaridade/genética , Anticorpos Anti-HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/metabolismo , Humanos , Polissacarídeos/metabolismo , Ligação Proteica
2.
Retrovirology ; 17(1): 24, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32762760

RESUMO

BACKGROUND: HIV-1 infects a wide range of CD4+ T cells with different phenotypic properties and differing expression levels of entry coreceptors. We sought to determine the viral tropism of subtype C (C-HIV) Envelope (Env) clones for different CD4+ T cell subsets and whether tropism changes during acute to chronic disease progression. HIV-1 envs were amplified from the plasma of five C-HIV infected women from three untreated time points; less than 2 months, 1-year and 3-years post-infection. Pseudoviruses were generated from Env clones, phenotyped for coreceptor usage and CD4+ T cell subset tropism was measured by flow cytometry. RESULTS: A total of 50 C-HIV envs were cloned and screened for functionality in pseudovirus infection assays. Phylogenetic and variable region characteristic analysis demonstrated evolution in envs between time points. We found 45 pseudoviruses were functional and all used CCR5 to mediate entry into NP2/CD4/CCR5 cells. In vitro infection assays showed transitional memory (TM) and effector memory (EM) CD4+ T cells were more frequently infected (median: 46% and 25% of total infected CD4+ T cells respectively) than naïve, stem cell memory, central memory and terminally differentiated cells. This was not due to these subsets contributing a higher proportion of the CD4+ T cell pool, rather these subsets were more susceptible to infection (median: 5.38% EM and 2.15% TM cells infected), consistent with heightened CCR5 expression on EM and TM cells. No inter- or intra-participant changes in CD4+ T cell subset tropism were observed across the three-time points. CONCLUSIONS: CD4+ T cell subsets that express more CCR5 were more susceptible to infection with C-HIV Envs, suggesting that these may be the major cellular targets during the first 3 years of infection. Moreover, we found that viral tropism for different CD4+ T cell subsets in vitro did not change between Envs cloned from acute to chronic disease stages. Finally, central memory, naïve and stem cell memory CD4+ T cell subsets were susceptible to infection, albeit inefficiently by Envs from all time-points, suggesting that direct infection of these cells may help establish the latent reservoir early in infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Subpopulações de Linfócitos T/imunologia , Tropismo Viral , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo , Adulto , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Feminino , Variação Genética , Infecções por HIV/imunologia , HIV-1/classificação , HIV-1/genética , Humanos , Memória Imunológica , Estudos Longitudinais , Filogenia , Receptores de HIV/metabolismo , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/virologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
3.
Nature ; 509(7498): 55-62, 2014 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-24590074

RESUMO

Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , Proteína gp160 do Envelope de HIV/química , Proteína gp160 do Envelope de HIV/imunologia , Vacinas contra a AIDS/química , Vacinas contra a AIDS/imunologia , Sequência de Aminoácidos , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/isolamento & purificação , Afinidade de Anticorpos/genética , Afinidade de Anticorpos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Sítios de Ligação/imunologia , Antígenos CD4/imunologia , Antígenos CD4/metabolismo , Linhagem da Célula , Regiões Determinantes de Complementaridade/química , Regiões Determinantes de Complementaridade/genética , Regiões Determinantes de Complementaridade/imunologia , Mapeamento de Epitopos , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Evolução Molecular , Anticorpos Anti-HIV/química , Anticorpos Anti-HIV/genética , Anticorpos Anti-HIV/isolamento & purificação , Infecções por HIV/imunologia , HIV-1/química , HIV-1/imunologia , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Testes de Neutralização , Estrutura Terciária de Proteína , Hipermutação Somática de Imunoglobulina/genética
4.
J Virol ; 87(9): 4882-94, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23408621

RESUMO

Broadly cross-neutralizing (BCN) antibodies are likely to be critical for an effective HIV vaccine. However, the ontogeny of such antibodies and their relationship with autologous viral evolution is unclear. Here, we characterized viral evolution in CAP256, a subtype C-infected individual who developed potent BCN antibodies targeting positions R166 and K169 in the V2 region. CAP256 was superinfected at 3 months postinfection with a virus that was highly sensitive to BCN V2-dependent monoclonal antibodies. The autologous neutralizing response in CAP256 was directed at V1V2, reaching extremely high titers (>1:40,000) against the superinfecting virus at 42 weeks, just 11 weeks prior to the development of the BCN response targeting the same region. Recombination between the primary and superinfecting viruses, especially in V2 and gp41, resulted in two distinct lineages by 4 years postinfection. Although neutralization of some CAP256 clones by plasma from as much as 2 years earlier suggested incomplete viral escape, nonetheless titers against later clones were reduced at least 40-fold to less than 1:1,000. Escape mutations were identified in each lineage, either at R166 or at K169, suggesting that strain-specific and BCN antibodies targeted overlapping epitopes. Furthermore, the early dependence of CAP256 neutralizing antibodies on the N160 glycan decreased with the onset of neutralization breadth, indicating a change in specificity. These data suggest rapid maturation, within 11 weeks, of CAP256 strain-specific antibodies to acquire breadth, with implications for the vaccine elicitation of BCN V2-dependent antibodies. Overall these studies demonstrate that ongoing viral escape is possible, even from BCN antibodies.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Sequência de Aminoácidos , Reações Cruzadas , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência
5.
Virol J ; 10: 347, 2013 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-24295501

RESUMO

BACKGROUND: Identification of the epitopes targeted by antibodies that can neutralize diverse HIV-1 strains can provide important clues for the design of a preventative vaccine. METHODS: We have developed a computational approach that can identify key amino acids within the HIV-1 envelope glycoprotein that influence sensitivity to broadly cross-neutralizing antibodies. Given a sequence alignment and neutralization titers for a panel of viruses, the method works by fitting a phylogenetic model that allows the amino acid frequencies at each site to depend on neutralization sensitivities. Sites at which viral evolution influences neutralization sensitivity were identified using Bayes factors (BFs) to compare the fit of this model to that of a null model in which sequences evolved independently of antibody sensitivity. Conformational epitopes were identified with a Metropolis algorithm that searched for a cluster of sites with large Bayes factors on the tertiary structure of the viral envelope. RESULTS: We applied our method to ID50 neutralization data generated from seven HIV-1 subtype C serum samples with neutralization breadth that had been tested against a multi-clade panel of 225 pseudoviruses for which envelope sequences were also available. For each sample, between two and four sites were identified that were strongly associated with neutralization sensitivity (2ln(BF) > 6), a subset of which were experimentally confirmed using site-directed mutagenesis. CONCLUSIONS: Our results provide strong support for the use of evolutionary models applied to cross-sectional viral neutralization data to identify the epitopes of serum antibodies that confer neutralization breadth.


Assuntos
Anticorpos Neutralizantes/imunologia , Reações Cruzadas , Epitopos/imunologia , Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Biologia Computacional/métodos , Epitopos/genética , HIV-1/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
6.
J Virol ; 85(7): 3128-41, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21270156

RESUMO

The targets of broadly cross-neutralizing (BCN) antibodies are of great interest in the HIV vaccine field. We have identified a subtype C HIV-1-superinfected individual, CAP256, with high-level BCN activity, and characterized the antibody specificity mediating breadth. CAP256 developed potent BCN activity peaking at 3 years postinfection, neutralizing 32 (76%) of 42 heterologous viruses, with titers of antibodies against some viruses exceeding 1:10,000. CAP256 showed a subtype bias, preferentially neutralizing subtype C and A viruses over subtype B viruses. CAP256 BCN serum targeted a quaternary epitope which included the V1V2 region. Further mapping identified residues F159, N160, L165, R166, D167, K169, and K171 (forming the FN/LRD-K-K motif) in the V2 region as crucial to the CAP256 epitope. However, the fine specificity of the BCN response varied over time and, while consistently dependent on R166 and K169, became gradually less dependent on D167 and K171, possibly contributing to the incremental increase in breadth over 4 years. The presence of an intact FN/LRD-K-K motif in heterologous viruses was associated with sensitivity, although the length of the adjacent V1 loop modulated the degree of sensitivity, with a shorter V1 region significantly associated with higher titers. Repair of the FN/LRD-K-K motif in resistant heterologous viruses conferred sensitivity, with titers sometimes exceeding 1:10,000. Comparison of the CAP256 epitope with that of the PG9/PG16 monoclonal antibodies suggested that these epitopes overlapped, adding to the mounting evidence that this may represent a common neutralization target that should be further investigated as a potential vaccine candidate.


Assuntos
Anticorpos Neutralizantes/sangue , Epitopos/imunologia , Anticorpos Anti-HIV/sangue , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Anticorpos Neutralizantes/imunologia , Reações Cruzadas , Mapeamento de Epitopos , Genótipo , Anticorpos Anti-HIV/imunologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Humanos , Testes de Neutralização , Plasma/imunologia
7.
Front Immunol ; 11: 984, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582155

RESUMO

We report here on HIV-1 immunization results in rabbits and macaques co-immunized with clade C gp160 DNA and gp140 trimeric envelope vaccines, a strategy similar to a recent clinical trial that showed improved speed and magnitude of humoral responses. Clade C envelopes were isolated from CAP257, an individual who developed a unique temporal pattern of neutralization breadth development, comprising three separate "Waves" targeting distinct Env epitopes and different HIV clades. We used phylogeny and neutralization criteria to down-select envelope vaccine candidates, and confirmed antigenicity of our antigens by interaction with well-characterized broadly neutralizing monoclonal antibodies. Using these envelopes, we performed rabbit studies that screened for immunogenicity of CAP257 Envs from timepoints preceding peak neutralization breadth in each Wave. Selected CAP257 envelopes from Waves 1 and 2, during the first 2 years of infection that were highly immunogenic in rabbits were then tested in macaques. We found that in rabbits and macaques, co-immunization of DNA, and protein envelope-based vaccines induced maximum binding and neutralizing antibody titers with three immunizations. No further benefit was obtained with additional immunizations. The vaccine strategies recapitulated the Wave-specific epitope targeting observed in the CAP257 participant, and elicited Tier 1A, 1B, and Tier 2 heterologous neutralization. CAP257 envelope immunogens also induced the development of ADCC and TFH responses in macaques, and these responses positively correlated with heterologous neutralization. Together, the results from two animal models in this study have implications for identifying effective vaccine immunogens. We used a multi-step strategy to (1) select an Env donor with well-characterized neutralization breadth development; (2) study Env phylogeny for potential immunogens circulating near peak breadth timepoints during the first 2 years of infection; (3) test down-selected Envs for antigenicity; (4) screen down-selected Envs in an effective vaccine regimen in rabbits; and (5) advance the most immunogenic Envs to NHP studies. The results were an induction of high titers of HIV-1 envelope-specific antibodies with increasing avidity and cross-clade neutralizing antibodies with effector functions that together may improve the potential for protection in a pre-clinical SHIV model.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Anticorpos Amplamente Neutralizantes/sangue , Anticorpos Anti-HIV/sangue , Proteína gp160 do Envelope de HIV/administração & dosagem , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Imunização , Imunogenicidade da Vacina , Produtos do Gene env do Vírus da Imunodeficiência Humana/administração & dosagem , Vacinas contra a AIDS/imunologia , Animais , Anticorpos Amplamente Neutralizantes/imunologia , Epitopos , Feminino , Anticorpos Anti-HIV/imunologia , Proteína gp160 do Envelope de HIV/genética , Proteína gp160 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , Imunidade Humoral , Macaca mulatta , Masculino , Coelhos , Fatores de Tempo , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
8.
Cell Rep ; 33(8): 108430, 2020 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33238131

RESUMO

Neutralizing antibodies (nAbs) to highly variable viral pathogens show remarkable diversification during infection, resulting in an "arms race" between virus and host. Studies of nAb lineages have shown how somatic hypermutation (SHM) in immunoglobulin (Ig)-variable regions enables maturing antibodies to neutralize emerging viral escape variants. However, the Ig-constant region (which determines isotype) can also influence epitope recognition. Here, we use longitudinal deep sequencing of an HIV-directed nAb lineage, CAP88-CH06, and identify several co-circulating isotypes (IgG3, IgG1, IgA1, IgG2, and IgA2), some of which share identical variable regions. First, we show that IgG3 and IgA1 isotypes are better able to neutralize longitudinal autologous viruses and epitope mutants than can IgG1. Second, detrimental class-switch recombination (CSR) events that resulted in reduced neutralization can be rescued by further CSR, which we term "switch redemption." Thus, CSR represents an additional immunological mechanism to counter viral escape from HIV-specific antibody responses.


Assuntos
HIV-1/imunologia , Switching de Imunoglobulina/imunologia , Testes de Neutralização/métodos , Humanos
9.
Cell Host Microbe ; 24(4): 593-599.e3, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30269971

RESUMO

Eliciting antibodies that neutralize a broad range of circulating HIV strains (broadly neutralizing antibodies [bnAbs]) represents a key priority for vaccine development. HIV superinfection (re-infection with a second strain following an established infection) has been associated with neutralization breadth, and can provide insights into how the immune system responds to sequential exposure to distinct HIV envelope glycoproteins (Env). Characterizing the neutralizing antibody (nAb) responses in four superinfected women revealed that superinfection does not boost memory nAb responses primed by the first infection or promote nAb responses to epitopes conserved in both infecting viruses. While one superinfected individual developed potent bnAbs, superinfection was likely not the driver as the nAb response did not target an epitope conserved in both viruses. Rather, sequential exposure led to nAbs specific to each Env but did not promote bnAb development. Thus, sequential immunization with heterologous Envs may not be sufficient to focus the immune response onto conserved epitopes.


Assuntos
Anticorpos Anti-HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , RNA Viral/imunologia , Superinfecção/virologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Anticorpos Neutralizantes/imunologia , Feminino , Células HEK293 , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , RNA Viral/sangue , RNA Viral/genética , Superinfecção/sangue , Superinfecção/complicações , Superinfecção/tratamento farmacológico , Tenofovir/uso terapêutico
10.
Cell Rep ; 25(11): 3123-3135.e6, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30540944

RESUMO

Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to the RV144 antibody CH58, but one lineage (CAP228-16H/19F) uses a light chain without the ED motif. A cocrystal structure of CAP228-16H bound to a V2 peptide identified a IGLV3-21 gene-encoded DDxD motif that is used to bind K169, with a mechanism that allows CAP228-16H to recognize more globally relevant V2 immunotypes. Overall, these data further our understanding of the development of cross-reactive, V2-binding, antiviral antibodies and effectively expand the human light chain repertoire able to respond to RV144-like immunogens.


Assuntos
Vacinas contra a AIDS/imunologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/química , Infecções por HIV/imunologia , Infecções por HIV/virologia , Cadeias Leves de Imunoglobulina/metabolismo , Lisina/metabolismo , Alelos , Sequência de Aminoácidos , Anticorpos Anti-HIV/isolamento & purificação , Proteína gp120 do Envelope de HIV/metabolismo , Humanos , Cadeias Leves de Imunoglobulina/química , Modelos Moleculares , Peptídeos/metabolismo , Ligação Proteica , Doadores de Tecidos
11.
Virology ; 446(1-2): 66-76, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24074568

RESUMO

We examined the ability of HIV-1 subtype C to develop resistance to the inhibitory lectins, griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN), which bind multiple mannose-rich glycans on gp120. Four primary HIV-1 strains cultured under escalating concentrations of these lectins became increasingly resistant tolerating 2 to 12 times their 50% inhibitory concentrations. Sequence analysis of gp120 showed that most had deletions of 1 to 5 mannose-rich glycans. Glycosylation sites at positions 230, 234, 241, 289 located in the C2 region and 339, 392 and 448 in the C3-C4 region were affected. Furthermore, deletions and insertions of up to 5 amino acids in the V4 region were observed in 3 of the 4 isolates. These data suggest that loss of glycosylation sites on gp120 as well as rearrangement of glycans in V4 are mechanisms involved in HIV-1 subtype C escape from GRFT, CV-N and SVN.


Assuntos
Antivirais/farmacologia , Proteínas de Bactérias/farmacologia , Proteínas de Transporte/farmacologia , Farmacorresistência Viral , HIV-1/efeitos dos fármacos , Lectinas/farmacologia , Lectinas de Plantas/farmacologia , Linhagem Celular , Tolerância a Medicamentos , Glicosilação , Proteína gp120 do Envelope de HIV/genética , HIV-1/genética , HIV-1/crescimento & desenvolvimento , Humanos , Concentração Inibidora 50 , Proteínas de Membrana , Testes de Sensibilidade Microbiana , Proteínas Mutantes/genética , Mutação de Sentido Incorreto , Análise de Sequência de DNA , Inoculações Seriadas
12.
Nat Med ; 18(11): 1688-92, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23086475

RESUMO

Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1-infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.


Assuntos
Anticorpos Neutralizantes , Epitopos , HIV-1 , HIV , Polissacarídeos , Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/uso terapêutico , Sequência de Aminoácidos , Anticorpos Neutralizantes/genética , Anticorpos Neutralizantes/imunologia , Especificidade de Anticorpos , Epitopos/genética , Epitopos/imunologia , Evolução Molecular , Feminino , Genoma Viral , HIV/genética , HIV/imunologia , HIV/patogenicidade , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , Soropositividade para HIV/genética , Soropositividade para HIV/imunologia , HIV-1/genética , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Testes de Neutralização , Polissacarídeos/genética , Polissacarídeos/imunologia
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