Antibody evolution to SARS-CoV-2 after single-dose Ad26.COV2.S vaccine in humans

Alice Cho1, Frauke Muecksch2, Zijun Wang1

  • 1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Insights

The Janssen Ad.26.COV.2 vaccine generates fewer memory B cells than mRNA vaccines, but these cells still offer comparable protection against SARS-CoV-2 variants. This explains why mRNA boosters are effective for Ad.26.COV.2 recipients.

Area of Science:

  • Immunology
  • Vaccinology
  • Virology

Background:

  • The single-dose Ad.26.COV.2 (Janssen) vaccine shows lower neutralizing antibody levels and reduced efficacy against SARS-CoV-2 infection and severe disease, particularly during the Omicron surge, compared to mRNA vaccines.
  • Understanding the memory B cell response is crucial for evaluating vaccine effectiveness and informing booster strategies.

Purpose of the Study:

  • To investigate the memory B cell response following a single dose of the Ad.26.COV.2 vaccine.
  • To compare the quantity and quality of memory B cell responses elicited by Ad.26.COV.2 vaccination versus mRNA vaccines.

Main Methods:

  • Analysis of memory B cell populations in Ad.26.COV.2 vaccine recipients at 1.5 and 6 months post-vaccination.
  • Comparison of RBD-specific memory B cell numbers and neutralizing antibody potency against SARS-CoV-2 variants (Wuhan-Hu-1, Delta, Omicron BA.1) between Ad.26.COV.2 and mRNA vaccine groups.

Main Results:

  • Ad.26.COV.2 recipients exhibited significantly lower numbers of RBD-specific memory B cells compared to mRNA vaccine recipients at both 1.5 and 6 months post-vaccination.
  • Despite quantitative differences, the quality of memory B cell responses was comparable, with elicited memory antibodies showing similar neutralizing potency against SARS-CoV-2 Wuhan-Hu-1, Delta, and Omicron BA.1 variants.

Conclusions:

  • The Ad.26.COV.2 vaccine elicits a lower quantity but comparable quality of memory B cell response relative to mRNA vaccines.
  • These findings support the effectiveness of mRNA vaccine boosting in Ad.26.COV.2 recipients and explain the vaccine's retained protective efficacy against severe disease during Omicron surges.