Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• The emergence of SARS-CoV-2 variants and novel coronaviruses highlights the need for broadly protective vaccines.
• Current vaccine strategies targeting the SARS-CoV-2 receptor-binding domain (RBD) show limitations against emerging variants.
• Betacoronaviruses, including SARS-CoV-1, SARS-CoV-2, and MERS-CoV, pose significant pandemic threats.

Purpose of the Study:

• To isolate and characterize broadly neutralizing antibodies (bnAbs) effective against multiple betacoronaviruses.
• To investigate the potential of targeting the conserved S2 region of the spike protein for broad coronavirus immunity.
• To inform the development of universal vaccines against pandemic betacoronaviruses.

Main Methods:

• Isolation of bnAbs from individuals vaccinated against and recovered from SARS-CoV-2.
• In vitro neutralization assays against SARS-CoV-1, SARS-CoV-2, and MERS-CoV.
• In vivo protection studies in animal models.
• Structural studies (e.g., cryo-EM) to determine antibody-antigen interactions.

Main Results:

• A panel of bnAbs targeting a conserved S2 region of the betacoronavirus spike fusion machinery was isolated.
• Selected bnAbs demonstrated broad in vivo protection against SARS-CoV-1, SARS-CoV-2, and MERS-CoV.
• Structural analyses revealed common antibody features responsible for broad reactivity against betacoronaviruses.

Conclusions:

• Antibodies targeting the conserved S2 region are crucial for broad protection against betacoronaviruses.
• These bnAbs offer promising avenues for antibody-based therapies and the development of pan-betacoronavirus vaccines.
• Identifying conserved targets like S2 is essential for future pandemic preparedness and vaccine design.