co evolution of a broadly neutralizing hiv 1 antibody and founder virus pdf

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

Journal of Immunology Research

Background

The Neutralizing Antibody Response to the HIV-1 Env Protein

Pritchard, Robyn L. Stanfield, Max Crispin, Andrew B.

Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers

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.

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

Journal of Immunology Research

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Current human immunodeficiency virus-1 HIV-1 vaccines elicit strain-specific neutralizing antibodies. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation.

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 A recombinant V3-region became fixed from 8 wpi, conferring slight neutralization resistance to CAP

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 ]. Therefore, the development of a safe and effective prophylactic HIV-1 vaccine would be the best for the ultimate elimination of the AIDS pandemic. However, no fully effective HIV vaccine is available till now.

Background

Metrics details. Broadly neutralizing antibodies bNAbs , able to prevent viral entry by diverse global viruses, are a major focus of HIV vaccine design, with data from animal studies confirming their ability to prevent HIV infection. However, traditional vaccine approaches have failed to elicit these types of antibodies. During chronic HIV infection, a subset of individuals develops bNAbs, some of which are extremely broad and potent.

A broadly neutralizing macaque monoclonal antibody against the HIV-1 V3-Glycan patch

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 Neutralizing Antibody Response to the HIV-1 Env Protein

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.

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. Gao and S. Alam and S.

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Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

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