Diverse BCR usage and T cell activation induced by different COVID-19 sequential vaccinations

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Limited understanding exists regarding SARS-CoV-2 specific antibody breadth and T cell differentiation across diverse COVID-19 sequential vaccination strategies.
• Comparing immunogenicity of third doses of mRNA, adenoviral vector, and recombinant protein vaccines is crucial for optimizing vaccination protocols.

Purpose of the Study:

• To compare the immunogenicity of sequential mRNA (I-I-M), adenoviral vector (I-I-A), and recombinant protein (I-I-R) COVID-19 vaccine strategies.
• To analyze differences in antibody response magnitude and breadth, and SARS-CoV-2 specific T and B cell differentiation.
• To provide insights guiding the selection of future vaccination strategies based on immune response profiles.

Main Methods:

• A single clinical trial cohort received sequential vaccinations with mRNA, adenoviral vector, or recombinant protein COVID-19 vaccines.
• Samples were assessed in the same laboratory to ensure consistency.
• Analysis included dominant B cell receptor (BCR) usage, RBD+ B cell activation, regulatory T cells, circulating T follicular helper cells (cTFH), and virus-specific CD4+ T cell responses.

Main Results:

• Distinct dominant BCR usages were observed for each vaccination strategy (IGHV1-69 for I-I-M, IGHV3-9 for I-I-A, IGHV4-34 for I-I-R), with comparable RBD+ B cell activation.
• The I-I-R group showed higher regulatory T cells, various cTFH subsets, and lower T cell proliferative capacity compared to I-I-M and I-I-A.
• The I-I-A group exhibited a higher proportion and number of virus-specific CD4+ T cells than the I-I-R group.

Conclusions:

• Sequential COVID-19 vaccination strategies induce distinct SARS-CoV-2 specific antibody profiles, BCR usage, and T/B cell activation patterns.
• Recombinant protein vaccines modulate T cell populations differently, while adenoviral vector vaccines enhance virus-specific CD4+ T cell responses.
• These findings offer valuable insights into the immunological mechanisms underlying vaccine efficacy and inform future vaccination strategy selection.