RESEARCH: ANTIBODY-AFFINITY-MATURATION
FOLDING PROJECT #18266 PROFILE

This project simulates how antibodies improve at fighting germs over time. They're using computer models to track changes in antibodies that have become very good at recognizing and neutralizing HIV and other viruses. This could help scientists design even better 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 fight infections.

Antibodies are specialized proteins created by your body's immune system to identify and neutralize harmful substances like bacteria, viruses, and fungi. They work by binding to specific targets on these invaders, 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.

Affinity maturation is a crucial step in the development of a strong immune response. During this process, B cells (a type of white blood cell) undergo genetic changes that enhance the ability of their produced antibodies to bind to specific antigens (foreign substances). This refinement leads to antibodies with higher affinity, meaning they can more effectively neutralize threats.

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antigens

Molecules that trigger an immune response.

Antigens are essentially the 'red flags' of your body's immune system. They are molecules found on the surface of bacteria, viruses, and other foreign invaders. When your immune system encounters an antigen, it recognizes it as a potential threat and mounts a defense.

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mutations

Changes in the DNA sequence.

Mutations are alterations in the genetic code (DNA) that can be caused by various factors like errors during cell division or exposure to radiation. These changes can affect the function of genes and lead to variations in traits.

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immune response

The body's reaction to infection or injury.

Your immune response is your body's complex system for protecting you from harmful invaders. When a threat is detected, specialized cells and molecules work together to identify, neutralize, and eliminate the danger.

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therapeutic

Relating to the treatment of disease.

A therapeutic refers to any substance or treatment intended to prevent, diagnose, or treat a medical condition. Pharmaceuticals and therapies are constantly being developed to combat various diseases.

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immunogens

Substances that stimulate an immune response.

Immunogens are the key components of vaccines. They are typically weakened or inactive forms of viruses or bacteria that trigger the immune system to produce antibodies against specific pathogens.

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HIV

Human Immunodeficiency Virus

HIV is a virus that attacks the body's immune system, specifically targeting CD4+ T cells. Over time, HIV can weaken the immune system, making individuals more susceptible to infections and diseases.

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gp120

Glycoprotein 120

Gp120 is a protein found on the surface of HIV. It plays a crucial role in the virus's ability to bind to and infect human cells.

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broadly neutralizing antibodies

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

Broadly neutralizing antibodies are highly effective because they can target conserved regions on viruses or bacteria, making them less likely to develop resistance.

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V3-glycan epitope

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

The V3-glycan epitope is a crucial binding site for some broadly neutralizing antibodies. Understanding its structure and function can help researchers develop new antiviral therapies.

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V2-apex epitope

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

The V2-apex epitope is another important binding site for broadly neutralizing antibodies. Targeting this region could offer new avenues for HIV treatment.