Research Update
August 15, 2022
Immune imprinting and COVID-19 immune responses
Research project at Dana Farber suggests immune imprinting as an explanation of differences in immune responses to SARS-CoV-2 based on strain of infection
Project Dates: May 2022 - August 2022
SARS-CoV-2 virus overview. The initial attachment of SARS-CoV-2 to cells involves specific binding between the viral Spike glycoprotein and the angiotensin-converting enzyme 2, ACE2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and pathogenic coronavirus that emerged in late 2019 and has caused a pandemic of acute respiratory disease. The initial attachment of SARS-CoV-2 to cells involves specific binding between the viral Spike glycoprotein and the cellular angiotensin-converting enzyme 2 receptor, ACE2. Structural studies have identified a complex between the receptor-binding domain (RBD), a subunit of the Spike, and the ACE2 receptor. Therefore, the Spike protein is the primary target for neutralizing antibodies and the principal antigen in most vaccines to date.
Infection or immunization can induce an antibody response for a range of epitopes specific to the Spike. However, many SARS-CoV-2 variants of concern (VOC) exhibit mutations in the RBD that efficiently escape the neutralizing antibody response raised by infection or currently approved vaccines. One explanation to this observation can be given by the phenomenon of immune imprinting, where initial exposure to one virus strain limits the development of immunity against new minor variant strains of the virus.
I analyzed antibody responses of triple vaccinated individuals infected with different SARS-CoV-2 strains to compare their antibody response towards each strain, their antibodies’ ability to bind to a range of variant Spikes, and their antibodies’ ability to neutralize a range of variant Spikes. I found that individuals infected with the Delta variant generally showed a robust anti-Spike IgG response compared to individuals infected with an Omicron variant strain. In addition, individuals infected with an Omicron strain showed a greater IgG binding bias for the Wuhan Spike compared to the BA.1 Spike and higher crossbinding activity for Wuhan and BA.1 RBD epitopes, pointing to immune imprinting.
Notes
Image credit: Yang, J., Petitjean, S. J., Koehler, M., Zhang, Q., Dumitru, A. C., Chen, W., Derclaye, S., Vincent, S. P., Soumillion, P., & Alsteens, D. (2020). Molecular interaction and inhibition of SARS-COV-2 binding to the ACE2 receptor. Nature Communications, 11(1).
I would like to thank Dr. Marasco, Hanzhong Ke, Matthew Chang, and the Marasco Lab for giving me this opportunity and for their guidance throughout this project.
