Co Evolution Of A Broadly Neutralizing Hiv 1 Antibody And Founder Virus Pdf
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- Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers
- Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
- A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch
Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers
Author s : Penny L. DOI : Background: A vaccine able to elicit broadly neutralizing antibodies capable of blocking infection by global viruses has not been achieved, and remains a key public health challenge. Objective: During infection, a robust strain-specific neutralizing response develops in most people, but only a subset of infected people develop broadly neutralizing antibodies. Understanding how and why these broadly neutralizing antibodies develop has been a focus of the HIV-1 vaccine field for many years, and has generated extraordinary insights into the neutralizing response to HIV-1 infection.
Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 HIV-1 -infected individuals. Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization BCN ability 1. In the present study, we report our findings on the evolution of host bNAb response over a period of 4 years in a subset of these individuals. Earlier studies have reported that in adults infected with HIV-1, bNAbs usually develop after 2—4 years of infection The autologous neutralizing response tends to be immunodominant, but when mutations occur in the variable epitopes V1—V5 in the viral envelope due to error prone reverse transcriptase activity, it leads to virus escape from neutralization These antibodies bind to the Env trimer and neutralize a broad spectrum of globally circulating HIV-1 strains 20 —
Similarly, a small number of macaques infected with SHIVs develop broadly neutralizing serologic activity, but less is known about the nature of simian antibodies. Ab neutralizes Ab binds the V3-glycan epitope in a glycan-dependent manner. The target epitopes of many bNAbs are unusual because they combine host-derived glycans with protein components of Env. Longitudinal cohort and structural studies demonstrated that bNAb maturation mediated by somatic hypermutation Wei et al. A number of structural studies have shown that the family of V3-glycan bNAbs is highly diverse.
Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
Therefore, the development of a safe and effective HIV-1 vaccine is on top of the global health priority. We believe that an effective HIV-1 vaccine, together with other prevention approaches, will bring an end to this epidemic in the near future. Now there are more than 35 million people living with HIV and 25 million individuals died of it. In , over people become newly infected with HIV every day [ 3 ]. Therefore, HIV cure is not possible until this reservoir is purged [ 7 ].
Developing HIV-1 vaccines that trigger broadly neutralizing antibodies bnAbs is a priority as bnAbs are considered key to elicitation of a protective immune response. To investigate whether the breadth of a neutralizing antibody nAb depended on the conservation of its epitope among circulating viruses, we examined Antibody:Envelope Ab:Env interactions and worldwide Env diversity. Neutralization breadth did not stem from the overall conservation of Ab epitopes but depended instead on the conservation of key sites of the Ab:Env interaction, revealing a mechanistic basis for neutralization breadth that could be exploited for vaccine design. So far, no HIV-1 vaccine has elicited broadly neutralizing antibodies bnAbs in humans. HIV-1, one of the most rapidly evolving pathogens, is remarkable for its high variability across individuals and adaptability within hosts. We tested the relationship between HIV-1 diversity and neutralization breadth.
A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch
Broadly neutralizing antibodies bNAbs are essential for a preventative HIV-1 vaccine but have not been elicited through vaccination. In these individuals, virus-antibody co-evolution is thought to drive the maturation of antibody lineages to neutralization breadth. We used deep sequencing of env genes and antibody transcripts from fourteen time points spanning the first 3 years of infection to characterize the virus-antibody co-evolution in donor CAP who developed V3-glycan-specific bNAbs. Sequencing and cloning of env genes, followed by neutralization assays, were used to identify Env mutations associated with neutralization escape from two bNAbs CAP G3 and CAP
Pritchard, Robyn L. Stanfield, Max Crispin, Andrew B. Moore, David Nemazee, Michel C.
Skip to search form Skip to main content You are currently offline. Some features of the site may not work correctly. DOI: Lynch and T. Zhou and F.
Original Research ARTICLE
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