Antibody modulation of B cell responses—Incorporating positive and negative feedback

Cyster, Jason G.; Wilson, Patrick C.

doi:10.1016/j.immuni.2024.06.009

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2024

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Cited by 7 publications

References 136 publications

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Vaccination against rapidly evolving pathogens and the entanglements of memory

Cobey

2024

Nat Immunol

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Vaccination against rapidly evolving pathogens and the entanglements of memory

Cobey

2024

Nat Immunol

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Trade-off between the antiviral and vaccinal effects of antibody therapy in the humoral response to HIV

Mittal,

Garg,

Desikan

et al. 2024

J. R. Soc. Interface.

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Antibody therapy for HIV-1 infection exerts two broad effects: a drug-like, antiviral effect, which rapidly lowers the viral load, and a vaccinal effect, which may control the viral load long-term by improving the immune response. Here, we elucidate a trade-off between these two effects as they pertain to the humoral response, which may compromise antibody therapy aimed at eliciting long-term HIV-1 remission. We developed a multi-scale computational model that combined within-host viral dynamics and stochastic simulations of the germinal centre (GC) reaction, enabling simultaneous quantification of the antiviral and vaccinal effects of antibody therapy. The model predicted that increasing antibody dosage or antibody–antigen affinity increased immune complex formation and enhanced GC output. Beyond a point, however, a strong antiviral effect reduced antigen levels substantially, extinguishing GCs and limiting the humoral response. We found signatures of this trade-off in clinical studies. Accounting for the trade-off could be important in optimizing antibody therapy for HIV-1 remission.

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Modulation of B cell receptor activation by antibody competition

He,

Guo,

Vahey

2024

Preprint

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During repeated virus exposure, pre-existing antibodies can mask viral epitopes by competing with B cell receptors for antigen. Although this phenomenon has the potential to steer B cell responses away from conserved epitopes, the factors that influence epitope masking by competing antibodies remain unclear. Using engineered, influenza-reactive B cells, we investigate how antibodies influence the accessibility of epitopes on the viral surface. We find that membrane-proximal epitopes on influenza hemagglutinin are fundamentally at a disadvantage for B cell recognition because they can be blocked by both directly and indirectly competing antibodies. While many influenza-specific antibodies can inhibit B cell activation, the potency of masking depends on proximity of the targeted epitopes as well as antibody affinity, kinetics, and valency. Although most antibodies are inhibitory, we identify one that can enhance accessibility of hidden viral epitopes. Together, these findings establish rules for epitope masking that could help advance immunogen design.

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Antibody modulation of B cell responses—Incorporating positive and negative feedback

Cited by 7 publications

References 136 publications

Vaccination against rapidly evolving pathogens and the entanglements of memory

Vaccination against rapidly evolving pathogens and the entanglements of memory

Trade-off between the antiviral and vaccinal effects of antibody therapy in the humoral response to HIV

Modulation of B cell receptor activation by antibody competition

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