Ad26.COV2.S priming provided a solid immunological base for mRNA-based COVID-19 booster vaccination

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• The emergence of SARS-CoV-2 variants necessitated booster vaccinations following initial Ad26.COV2.S priming.
• Previous studies indicated heterologous boosters elicit high antibody levels, but their impact on other immune functions was unclear.

Purpose of the Study:

• To investigate the effects of homologous and heterologous (mRNA-1273 or BNT162b2) booster vaccinations on the immune response in Ad26.COV2.S-primed individuals.
• To assess changes in functional antibodies and T-cell responses against SARS-CoV-2 and its variants post-booster.

Main Methods:

• Immunological profiling of individuals primed with Ad26.COV2.S.
• Analysis of samples before and after homologous or heterologous booster vaccination.
• Measurement of functional antibodies and T-cell responses, including cross-reactivity to variants.

Main Results:

• Booster vaccinations significantly increased functional antibodies targeting both ancestral SARS-CoV-2 and emerging variants.
• Heterologous boosters, in particular, induced high levels of functional antibodies.
• T-cell responses showed similar magnitudes after homologous or heterologous boosting and maintained cross-reactivity against variants.
• Minimal expansion of SARS-CoV-2-specific T-cell clones and no increase in T-cell repertoire breadth were observed.

Conclusions:

• Ad26.COV2.S priming establishes a robust foundation for heterologous boosting.
• Heterologous boosting enhances both humoral and cellular immune responses against SARS-CoV-2 variants of concern.