RESEARCH: ANTIBODY-DYNAMICS
FOLDING PROJECT #18268 PROFILE

This project simulates how antibodies evolve to fight infections better. By studying these simulations, scientists hope to design new drugs and vaccines that are even more effective.

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 made by your immune system. They recognize and attach to harmful invaders like bacteria and viruses, marking them for destruction. Each antibody is designed to target a specific invader, like a key fitting into a lock.

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affinity maturation

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

Affinity maturation is like a refining process for antibodies. When your body encounters an infection, your immune system produces many different antibodies. Over time, the antibodies that bind most strongly to the invader (have high affinity) are favored and replicated. This makes the immune response more effective at fighting off the infection.

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antigen

A molecule that triggers an immune response.

Antigens are like flags on invaders (bacteria, viruses, etc.) that alert your immune system. When your body recognizes an antigen as foreign, it mounts an immune response to try and eliminate the threat.

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HIV

Human Immunodeficiency Virus

HIV is a virus that attacks the body's immune system, specifically the CD4+ T cells. Over time, HIV can weaken the immune system to the point where it can no longer fight off infections and diseases, leading to AIDS (Acquired Immune Deficiency Syndrome).

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gp120

Glycoprotein 120

gp120 is a protein found on the surface of the HIV virus. It's responsible for binding to receptors on human cells, allowing the virus to enter and infect them.

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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. They're designed to target multiple parts of a virus, making them effective against a wide variety of its strains. This is particularly important for viruses like HIV, which mutate rapidly and can develop resistance to traditional 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 unique feature on the surface of the HIV virus. Certain antibodies, like those in the PGT121 lineage, are designed to target this region and neutralize the virus.

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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 unique feature on the surface of the HIV virus. Certain antibodies, like those in the CAP256-VRC26 lineage, are designed to target this region and neutralize the virus.