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Use of an Influenza Antigen Microarray to Measure the Breadth of Serum Antibodies Across Virus Subtypes

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Humoral Immunity Profiling to Pandemic and Bat-Derived Coronavirus Variants: A Geographical Comparison.

Parinaz Fathi¹, Andrea Lucia Alfonso¹, Christina Yek²

¹Section on Immunoengineering, Biomedical Engineering and Technology Acceleration Center, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD, 20892, USA.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)

|October 29, 2024

Summary

Pre-pandemic exposure to related betacoronaviruses in Cambodia may have provided cross-reactive immunity to SARS-CoV-2 (SCV2). This finding offers insights into lower SCV2 severity in Southeast Asia.

Keywords:

SARS‐CoV‐2 antibodies bats betacoronaviruses cross‐reactivity

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Area of Science:

Virology
Immunology
Epidemiology

Background:

Dynamic pathogen exposure can influence immunological responses to novel viruses like SARS-CoV-2 (SCV2).
Southeast Asia's lower rates of severe SCV2 morbidity and mortality may be linked to prior exposure to related betacoronaviruses.
SCV2-related betacoronaviruses have been identified in bats in Southeast Asia, indicating potential for bat-to-human spillover events.

Purpose of the Study:

To investigate the presence of antibodies to SCV2 and a related bat coronavirus (RshSTT182) in pre-pandemic Cambodian human sera.
To determine if pre-existing cross-reactive immunity to SCV2 was present in the Cambodian population before the global pandemic.

Main Methods:

Serum samples from 293 Cambodians (pre-pandemic) were tested using ELISA assays for antibodies against SCV2 and RshSTT182.
Seropositive samples were further analyzed for antibody levels and cross-reactivity using competitive binding ELISA.
Surrogate virus neutralization tests were performed to assess neutralizing activity against SCV2 and related betacoronaviruses.

Main Results:

10.9% of pre-pandemic Cambodian sera were seropositive for SCV2.
Half of the SCV2 seropositive samples showed higher antibody levels to the bat coronavirus RshSTT182.
Competitive binding assays confirmed cross-reactivity, and neutralization tests indicated activity against SCV2 and related viruses.

Conclusions:

Exposure to related betacoronaviruses prior to the COVID-19 pandemic may induce cross-reactive immune responses to SCV2.
This cross-reactivity could be a contributing factor to the observed lower SCV2 severity in Southeast Asia.
Findings highlight the importance of understanding endemic coronaviruses in predicting responses to novel viral threats.