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

Abstract

The single dose Ad.26.COV.2 (Janssen) vaccine elicits lower levels of neutralizing antibodies and shows more limited efficacy in protection against infection than either of the available mRNA vaccines. In addition, the Ad.26.COV.2 has been less effective in protection against severe disease during the Omicron surge. Here, we examined the memory B cell response to single dose Ad.26.COV.2 vaccination. Compared to mRNA vaccines, Ad.26.COV.2 recipients had significantly lower numbers of RBD-specific memory B cells 1.5 or 6 months after vaccination. Memory antibodies elicited by both vaccine types show comparable neutralizing potency against SARS-CoV-2 and Delta. However, the number of memory cells producing Omicron neutralizing antibodies was somewhat lower after Ad.26.COV.2 than mRNA vaccination. The data help explain why boosting Ad.26.COV.2 vaccine recipients with mRNA vaccines is effective, and why the Janssen vaccine appears to have been less protective against severe disease during the Omicron surge than the mRNA vaccine.

Humoral immunity to SARS-CoV-2 elicited by combination COVID-19 vaccination regimens

“… a, Vaccination and blood donation schedules for mRNA vaccinees (upper panel), Ad26.COV.2S (Janssen) vaccinees (middle panel), and ChAdOx1 (AZ) vaccinees boosted with either BNT162b2 (BNT, upper half of lower panel) or AZ (lower half of lower panel). b, Area under the curve (AUC) for plasma IgG antibody binding to SARS-CoV-2 Wuhan-Hu-1 RBD 1 month (m) after mRNA prime (Cho et al, 2021), or Janssen Ad26.COV.2S prime (Cho et al, 2022) or AZ prime, as well as 4 months or 6 months after the initial AZ prime (AZ/BNT; n=26) or (AZ/AZ; n=23). Lines connect longitudinal samples.…”

“…c, Number of Wuhan- Hu-1 RBD-specific B cells per 10 M B cells for AZ vaccinees 1 m after prime compared to AZ/BNT and AZ/AZ vaccinees 6 m after initial dose. d, Number of Wuhan-Hu-1 RBD-specific B cells per 10 M B cells for mRNA vaccinees 6 m after initial dose (Cho et al, 2021) and Janssen Ad26.COV2.S vaccinees 6 m after prime (Cho et al, 2022) compared to AZ/BNT and AZ/AZ vaccinees 6 m after initial dose. e, Pie charts show the distribution of antibody sequences obtained from Wuhan-Hu-1 RBD-specific memory B cells of mRNA vaccinees 6 m after initial dose and Ad26.COV.2S (Janssen) vaccinees 6 m after initial prime, or AZ/BNT and AZ/AZ vaccinees 6 m after initial dose.…”

“…c, Graphs show anti-SARS-CoV-2 neutralizing activity of monoclonal antibodies measured by a SARS-CoV-2 pseudotype virus neutralization assay using wild-type (Wuhan-Hu-1 (Wu et al, 2020)) (SARS-CoV-2 pseudovirus (Robbiani et al, 2020;Schmidt et al, 2020)) for antibodies cloned from mRNA vaccinees and 6 m after initial dose (n=262) (Cho et al, 2021), or from Janssen Ad26.COV2.S vaccinees (n=95) 6 m after prime (Cho et al, 2022), compared to antibodies cloned from AZ/BNT (n=189) and AZ/AZ (n=94) vaccinees 6 m after initial dose. d. Pie charts indicated the frequency of neutralizing (IC50<1000 ng/mL, white) vs. non-neutralizing (IC50>1000 ng/mL, black) antibodies cloned from mRNA vaccinees (Cho et al, 2021), Janssen Ad26.COV2.S vaccinees (Cho et al, 2022) Results of epitope mapping performed by competition BLI, comparing mAbs cloned from Janssen vaccinees 6 m (n=33) after prime (Cho et al, 2022) and mAbs cloned from mRNA vaccinees 6 m after initial dose (n=68) (Cho et al, 2021), to mAbs cloned from AZ/AZ (n=62) or AZ/BNT(n=66) vaccinees 6 m after initial dose. a, Pie charts show the distribution of the antibody classes among all RBD-binding antibodies, Wuhan-Hu-1 neutralizing antibodies only or non-neutralizing antibodies only.…”

“…The latter is likely to be particularly important for recall responses and protection from severe diseases upon repeated viral challenge (Amanna et al, 2007;Mesin et al, 2020). for plasma IgG antibody binding to SARS-CoV-2 Wuhan-Hu-1 RBD 1 month (m) after mRNA prime (Cho et al, 2021), or Janssen Ad26.COV.2S prime (Cho et al, 2022) or AZ prime, as well as 4 months or 6 months after the initial AZ prime (AZ/BNT; n=26) or (AZ/AZ; n=23). Lines connect longitudinal samples.…”

“…Lines connect longitudinal samples. c-e, AUC for plasma IgG binding to Wuhan-Hu-1 RBD in vaccinees 1 m after AZ prime compared to mRNA prime (Cho et al, 2021) or Janssen Ad26.COV2.S (Cho et al, 2022) prime at similar timepoint (c) , mRNA vaccinees 2.3 m after initial dose (Cho et al, 2021) compared to AZ/BNT and AZ/AZ vaccinees 4 m after initial dose (d), or mRNA vaccinees 6 m after initial dose (Cho et al, 2021) and Janssen Ad26.COV2.S vaccinees 6 m after one dose (Cho et al, 2022) compared to AZ/BNT and AZ/AZ vaccinees 6 m after initial dose (e). f-i, Anti-SARS-CoV-2 NT50s of plasma measured by a SARS-CoV-2 pseudotype virus neutralization assay using wild-type (Wuhan-Hu-1 (Wu et al, 2020)) SARS-CoV-2 pseudovirus (Robbiani et al, 2020;Schmidt et al, 2020) in plasma samples shown in panels a-e. j-m, Plasma neutralizing activity against indicated SARS-CoV-2 Delta (j) and Omicron (k) variants for n=24 (AZ/BNT: n=12 and AZ/AZ:n=12) randomly selected samples assayed in HT1080Ace2 cl.14 cells.…”