RESEARCH: ANTIBODY-AFFINITY-MATURATION
FOLDING PROJECT #18273 PROFILE

This project simulates how antibodies evolve to better fight infections. By tracking changes in antibody structure over time, scientists hope to design more effective vaccines and treatments for diseases like HIV.

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 fight infections.

Antibodies are specialized proteins created by your immune system to target and neutralize harmful invaders like bacteria, viruses, and fungi. They work by binding to specific parts of these invaders, marking them for destruction or preventing them from causing harm.

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Affinity Maturation

The process by which antibodies increase in affinity (binding strength) for an antigen over time.

Affinity maturation is a key step in the development of a strong and specific immune response. During this process, B cells that produce antibodies undergo mutations in their genes, leading to changes in the structure of the antibody proteins. Some of these mutations result in antibodies with a stronger affinity for the target antigen (the substance being attacked by the immune system). These high-affinity antibodies are then selected and replicated, providing long-lasting protection against the specific pathogen.

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Antigen

A molecule that triggers an immune response.

Antigens are substances, often found on the surface of pathogens (like bacteria or viruses), that can be recognized by the immune system. When an antigen enters the body, it is detected by specialized cells called lymphocytes. These cells then initiate an immune response to eliminate the threat.

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B Cell

A type of white blood cell that produces antibodies.

B cells are a crucial part of the adaptive immune system. They have receptors on their surface that can bind to specific antigens. When a B cell encounters its matching antigen, it becomes activated and starts producing antibodies. These antibodies then circulate throughout the body, targeting and neutralizing the specific pathogen that triggered the immune response.

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HIV

Human Immunodeficiency Virus

HIV is a virus that attacks the immune system, specifically targeting CD4+ T cells. Over time, HIV infection can lead to Acquired Immunodeficiency Syndrome (AIDS), a condition where the body's ability to fight infections is severely weakened.

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gp120

A glycoprotein found on the surface of the HIV envelope.

gp120 is a crucial protein on the surface of the HIV virus. It plays a key role in attaching to and entering host cells. Antibodies that target gp120 can help prevent HIV infection by blocking this attachment.

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Broadly Neutralizing Antibody

An antibody that can neutralize a wide range of different HIV strains.

Broadly neutralizing antibodies (bNAbs) are highly sought-after in the fight against HIV. They can recognize and bind to multiple, diverse strains of the virus, offering a broader protection against infection.

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V3-glycan Epitope

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

The V3-glycan epitope is a crucial target for some broadly neutralizing antibodies. Antibodies that bind to this region can effectively block HIV from attaching to and entering host cells.

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V2-apex Epitope

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

The V2-apex epitope is another important target for broadly neutralizing antibodies. Antibodies that bind to this region can also effectively block HIV from attaching to and entering host cells.