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Exploring a New Avenue in Vaccine Development: Targeting Conserved Epitopes with Broadly Neutralizing Antibodies


SARS-CoV-2’s ability to evolve quickly creates ongoing challenges for vaccine development. The spike protein, critical for the virus’s cell infection, undergoes rapid mutations, making antibodies less effective against new strains. Traditional vaccines, with their lengthy development and testing timelines, struggle to predict these evolutionary changes accurately, leading to a constant struggle to keep pace with the virus.

In a study published in Science Translational Medicine, researchers from the NIH-NIAID aimed to identify novel epitopes on the spike protein that evolve less rapidly. By sidestepping the most rapidly evolving areas, the researchers sought to discover antibodies capable of neutralizing multiple strains, including those not yet identified. This approach aims to establish a more sustainable method of countering the virus without relying on rapid vaccine adaptation.

Harnessing the Power of the Beacon® System for Rapid Antibody Screening

The study involved an in-depth analysis of plasma samples from 142 donors to identify candidates with broad reactivity against seven coronavirus strains. From this pool, 19 donors were chosen for isolating monoclonal antibodies. Bruker’s Beacon® system played a crucial role in rapidly screening activated memory B cells to identify cross-reactive monoclonal antibody sequences against three of the seven strains.

The Beacon system facilitated the swift screening of individual antibody secreting clones, identifying 60 monoclonal antibodies exhibiting reactivity against three strains, and of which six rare candidates with cross-reactivity against all seven coronaviruses. Further, these six antibodies targeted a highly conserved motif on the fusion peptide region across 34 viral isolates in four genera.

Extending Protection to a Wider Range of Current and Prospective Coronaviruses

Utilizing the six antibodies identified via the Beacon system, researchers identified a novel epitope on the fusion peptide region. This epitope displayed a high degree of conservation across multiple viral isolates and demonstrated neutralization against SARS-CoV-2. In a Syrian hamster model, some of these antibodies were able to limit disease severity.

This less commonly targeted epitope, not frequently observed in convalescent patients or Moderna mRNA-1273 vaccinated individuals, holds promise for vaccine development. It may offer a more stable solution to the challenges posed by the virus’s rapid evolution, potentially providing broader protection against both current and future coronaviruses.

Shaping Future Responses to Viral Evolution

The study’s focus on identifying broadly neutralizing antibodies targeting less-evolving epitopes, enabled by the Beacon System, represents a step forward in the ongoing battle against COVID-19. The NIH’s approach offers a potential avenue for vaccine development, contributing to our ability to respond effectively to the virus’s evolutionary changes.

This method isn’t confined to coronaviruses alone; its applications extend to other viral threats, including HIV. As stated in the study, “These findings have parallels to studies of HIV-1 gp120, where the surface-exposed fusion peptide was identified as a target of neutralizing mAbs.” The study’s success marks a meaningful progression in our ability to navigate evolving viral challenges.

Read our Application Note to learn how you can experience unprecedented speed in antibody discovery with the Opto® B discovery application on the Beacon system.

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