RESEARCH: ANTIBODY-AFFINITY-MATURATION
FOLDING PROJECT #18271 PROFILE

This project uses computer simulations to study how antibodies change and become better at fighting viruses. They're focusing on well-known antibody families that target HIV, looking at both their original form and their evolved, stronger forms. The goal is to understand how these changes happen so scientists can design even more powerful antibodies for vaccines and 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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Antibodies

Proteins 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 binding to specific parts of these invaders, marking them for destruction by other immune cells.

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Antigens

Molecules that trigger an immune response.

Antigens are substances that can trigger a response from our immune system. They are often found on the surface of bacteria, viruses, or other foreign invaders. When our body detects an antigen, it launches an immune response to try and eliminate the threat.

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Affinity Maturation

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

Affinity maturation is a key step in the development of a strong immune response. During this process, B cells (a type of white blood cell) undergo mutations that can improve the ability of their antibodies to bind to specific antigens. This makes the immune system more efficient at recognizing and eliminating threats.

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Humoral Immune Response

An immune response mediated by antibodies.

The humoral immune response is a branch of the adaptive immune system that involves the production of antibodies. These antibodies circulate in the body fluids (humors) and can bind to and neutralize pathogens, marking them for destruction.

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Antibodies Therapeutics

Medicines that use antibodies to treat diseases.

Antibody therapeutics are a type of medicine that uses specially designed antibodies to target and treat specific diseases. They can be used to block the action of harmful proteins, deliver drugs to cancer cells, or boost the immune system's ability to fight infection.

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Vaccine Immunogens

Substances that stimulate an immune response and provide immunity against a specific disease.

Vaccine immunogens are the components of vaccines that trigger an immune response. They can be weakened or inactive forms of viruses or bacteria, or they can be parts of these pathogens, like proteins or sugars. The goal is to teach the body's immune system to recognize and fight off the real disease.

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HIV

Human Immunodeficiency Virus.

HIV is a virus that attacks the immune system, specifically the CD4+ T cells. This weakens the body's ability to fight off infections and can lead to AIDS (Acquired Immunodeficiency Syndrome). There are effective treatments available to manage HIV infection but there is currently no cure.

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gp120

Glycoprotein 120, a surface protein of the HIV virus.

gp120 is a key 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. Antibodies that target gp120 are important for neutralizing HIV infection.

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Broadly Neutralizing Antibodies

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

Broadly neutralizing antibodies (bnAbs) are a powerful type of antibody that can target and neutralize a broad range of different HIV strains. They are highly sought after as potential therapeutic agents for HIV because they could provide long-lasting protection against infection.

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V3-glycan Epitope

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

The V3-glycan epitope is a specific binding site on the HIV envelope protein gp120. It's a common target for neutralizing antibodies, and some broadly neutralizing antibodies specifically recognize this region.

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V2-apex Epitope

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

The V2-apex epitope is another important binding site on the HIV envelope protein gp120. Some broadly neutralizing antibodies target this region to neutralize the virus.

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Simulations

Computer programs that mimic real-world processes.

Simulations are computer models that recreate real-world systems or processes. They can be used to study complex phenomena, predict outcomes, and test different scenarios without the need for physical experiments.