Cross-Reactive Coronavirus Antibodies and Vaccine Development

Overview of Coronaviruses

Patients exposed to coronaviruses may generate a versatile, cross-reactive antibody that could contribute to the development of a broad-acting vaccine. There are seven known human coronavirus types, four of which—OC43, HKU1, 229E, and NL63—are responsible for the common cold. Most individuals encounter at least one of these four coronaviruses during their lifetime. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, is another member of this family. Infections with cold-causing coronaviruses can lead to immune memory, potentially influencing the immune response to COVID-19.

Research Findings

A study published in Nature Communications compared blood samples from patients collected prior to the pandemic to those who tested positive for COVID-19. This comparison revealed antibody types that cross-react with other coronaviruses as well as SARS-CoV-2.

Discovery of Cross-Reactive Antibodies

Researchers found that a cross-reactive coronavirus antibody is elicited directly by COVID-19 infection. Dr. Raiees Andrabi, a senior author of the study, noted, “We were able to determine that this type of cross-reactive antibody is likely produced by a memory B cell that’s initially exposed to a coronavirus that causes the common cold and is then recalled during a COVID-19 infection.” Memory B cells are long-lasting and can circulate in the body for decades, enabling rapid antibody production against previously encountered pathogens. Although evidence of pre-existing cross-reactive memory B cells triggered by SARS-CoV-2 infection was found, there was only limited evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in samples collected before the pandemic. Nevertheless, researchers identified one cross-reactive neutralizing antibody specific to the S2 subunit of the spike (S) protein.

Mechanism of Action

The researchers utilized electron microscopy to observe how the cross-reactive antibody neutralizes various coronaviruses, including SARS-CoV-2. They discovered that the antibody typically binds to the S protein of the virus, a region that appears consistent across different coronavirus strains. Ge Song, the first author of the paper, emphasized, “The study highlights how important it is to fully understand the nature of pre-existing immunity, especially in regard to coronaviruses. Earlier exposure to a coronavirus, even a virus that causes mild colds, impacts the nature and level of antibodies produced when more serious coronavirus threats emerge.”

Implications for Vaccine Development

The findings of this study hold significant potential for vaccination strategies, as immunological memory is foundational for effective vaccines. The research may pave the way for developing a vaccine or antibody treatment effective against a range of coronaviruses. Further investigation into pre-existing immunity to endemic coronaviruses is necessary to evaluate antibody responses to SARS-CoV-2. Co-author Dr. Dennis Burton stated, “Another deadly coronavirus will likely emerge again in the future – and when it does, we want to be better prepared. Our identification of a cross-reactive antibody against SARS-CoV-2 and the more common coronaviruses is a promising development on the way to a broad-acting vaccine or therapy.”

References

1. Song, G., et al. (2021). Cross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection. Nature Communications, 12(1), 1-10. Retrieved from: https://www.nature.com/articles/s41467-021-23074-3
2. Versatile coronavirus antibody may be starting point for broader-acting vaccines (2021). EurekAlert! Retrieved from: https://www.eurekalert.org/pub_releases/2021-05/sri-vca052721.php
3. Quast, I. and Tarlinton, D. (2021). B cell memory: understanding COVID-19. Immunity, 54(2), 205-210. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826135/