RESEARCH: ANTIBODY-AFFINITY-MATURATION
FOLDING PROJECT #18267 PROFILE

Scientists are using computer simulations to understand how antibodies change and become better at fighting viruses like HIV. They're looking at real antibody families to see how their shape and function evolve. This could lead to new, more effective treatments.

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 the body's immune system to fight off infections. They recognize and bind to specific invaders like bacteria or viruses, marking them for destruction by other immune cells.

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affinity maturation

The process by which antibodies become more effective at binding to their target antigens over time

Affinity maturation is a key part of the immune system's learning process. When exposed to a pathogen, B cells produce antibodies that gradually improve their ability to bind to the invader. This makes the immune response stronger and more specific.

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antigen

A molecule that triggers an immune response

Antigens are the molecules that alert the immune system to the presence of a foreign invader. They can be parts of bacteria, viruses, or other harmful substances.

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HIV

Human Immunodeficiency Virus

HIV is a virus that attacks the body's immune system, specifically targeting CD4+ T cells. This weakens the immune system, making people more vulnerable to infections and diseases.

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gp120

Glycoprotein 120, a surface protein on the HIV virus

gp120 is a key protein found on the surface of the HIV virus. It plays a crucial role in helping the virus 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 a type of antibody that can target multiple strains of a virus. They are highly valuable for developing treatments and vaccines because they offer broader protection against diverse viral variants.