RESEARCH: ANTIBODY-AFFINITY-MATURATION
FOLDING PROJECT #18272 PROFILE

This project uses computer simulations to understand how antibodies become better at fighting viruses like HIV. Scientists will track the changes in antibodies over time, looking at both their variable and constant regions. The goal is to learn how antibodies develop high-affinity for their targets, which can help create more effective antibody drugs and vaccines.

Note: This TLDR is a simplication and may not be 100% accurate.

In their response to antigens, antibodies undergo a process called affinity maturation where they pick up mutations that help increase their affinity for the antigen.

This is an integral part of the humoral immune response.

There are tools to decode what these mutations are, but the role of these mutations in influencing antibody dynamics remains largely unclear.

Understanding how antibody dynamics change throughout the course of affinity maturation would help in designing highly specific antibody therapeutics and vaccine immunogens.
This project aims to simulate a range of antibody affinity maturation pathways.

We have multiple lineages we would like to track.

These are all lineages that have led to potent antibodies and have published structures available.

For each lineage, we are simulating a naïve antibody and a mature antibody.

Similar studies conducted in the past have used short
simulations and have simulated only the variable regions of the proteins.

Here, we will generate large simulation datasets that include the constant regions as well as the variable regions, giving us a more accurate glimpse into antibody dynamics.

Our hope is that these simulations will uncover the dynamics that are responsible for highly specific and potent antibodies, helping to improve antibody design in the future.
p18265 – PGT121 lineage, naïve antibody.

The PGT121 lineage antibodies
are broadly neutralizing antibodies that bind to the V3-glycan epitope on
the HIV envelope protein gp120.
p18266 – PGT121 lineage, mature antibody.

The PGT121 lineage antibodies
are broadly neutralizing antibodies that bind to the V3-glycan epitope on
the HIV envelope protein gp120.
p18267 – CAP256-VRC26 lineage, naïve antibody.

The CAP256-VRC26
lineage antibodies are broadly neutralizing antibodies that bind to the V2-
apex epitope on the HIV envelope protein gp120.
p18268 – CAP256-VRC26, mature antibody.

The CAP256-VRC26 lineage
antibodies are broadly neutralizing antibodies that bind to the V2-apex
epitope on the HIV envelope protein gp120.
p18569 – CH65-CH67 lineage, naïve antibody.

The CH65-CH67 lineage
antibodies bind to the receptor binding site on the influenza hemagglutinin
protein. p18270 – CH65-CH67 lineage, mature antibody.

The CH65-CH67 lineage
antibodies bind to the receptor binding site on the influenza hemagglutinin
protein.
p18271 – CH103 lineage, naïve antibody.

The CH103 lineage antibodies are
broadly neutralizing antibodies that bind to the CD4 binding site epitope on
the HIV envelope protein gp120.
p18272 – CH103 lineage, mature antibody.

The CH103 lineage antibodies
are broadly neutralizing antibodies that bind to the CD4 binding site epitope
on the HIV envelope protein gp120.
p18273 – 1-18 lineage, naïve antibody.

The 1-18 lineage antibodies bind to
the CD4 binding site on the HIV envelope protein gp120.
p18274 – 1-18 lineage, mature antibody.

The 1-18 lineage antibodies are
broadly neutralizing antibodies that bind to the CD4 binding site on the HIV
envelope protein gp120.

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Antibody

A protein produced by the immune system to neutralize pathogens.

Antibodies are specialized proteins created by our immune system to fight off harmful invaders like bacteria and viruses. They work by recognizing and attaching to specific parts of these invaders, marking them for destruction.

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Affinity Maturation

The process by which antibodies increase their binding affinity to an antigen over time.

Affinity maturation is a key process in the immune system where antibodies become better and better at recognizing and attaching to specific invaders (antigens). This happens through mutations that refine the antibody's shape, allowing it to bind more tightly.

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Antigen

A molecule that triggers an immune response.

Antigens are essentially the 'enemy' signals that our immune system recognizes. They can be parts of bacteria, viruses, or even our own cells when they become abnormal. The immune system uses antigens to identify and target harmful invaders.

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HIV

Human Immunodeficiency Virus

HIV is a virus that attacks the body's immune system, specifically the cells that help fight off infections. If left untreated, HIV can lead to AIDS (Acquired Immunodeficiency Syndrome).

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gp120

Glycoprotein 120

gp120 is a protein found on the surface of the HIV virus. It plays a crucial role in allowing the virus to attach to and enter human cells.

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Broadly Neutralizing Antibodies

Antibodies that can neutralize a wide range of different strains of a virus.

Broadly neutralizing antibodies are like super-powered antibodies that can fight off many different versions of a virus. This is particularly important for viruses like HIV, which mutate rapidly and develop resistance to standard treatments.

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V3-glycan Epitope

A specific region on the HIV envelope protein gp120 that is recognized by certain antibodies.

The V3-glycan epitope is a vulnerable spot on the surface of the HIV virus. Some antibodies specifically target this site to block the virus from entering human cells.

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V2-apex Epitope

A specific region on the HIV envelope protein gp120 that is recognized by certain antibodies.

The V2-apex epitope is another vulnerable spot on the surface of the HIV virus. Some antibodies specifically target this site to block the virus from entering human cells.

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Lineage

A group of related antibodies that share a common ancestor.

In antibody research, a lineage refers to a family of similar antibodies that evolved from a single original antibody. Tracking these lineages helps scientists understand how antibodies change and improve over time.