Vaccination with BNT162b2 and ChAdOx1 nCoV-19 Induces Cross-Reactive Anti-RBD IgG against SARS-CoV-2 Variants including Omicron

Daniela Gerges, Sebastian Kapps, Esperanza Hernández-Carralero, Raimundo Freire, Monika Aiad, Sophie Schmidt, Wolfgang Winnicki, Thomas Reiter, Sahra Pajenda, Alice Schmidt, Gere Sunder-Plassmann, Ludwig Wagner, Daniela Gerges, Sebastian Kapps, Esperanza Hernández-Carralero, Raimundo Freire, Monika Aiad, Sophie Schmidt, Wolfgang Winnicki, Thomas Reiter, Sahra Pajenda, Alice Schmidt, Gere Sunder-Plassmann, Ludwig Wagner

Abstract

SARS-CoV-2 variants of concern (VOCs) have caused a significant increase in infections worldwide. Despite high vaccination rates in industrialized countries, the fourth VOC, Omicron, has outpaced the Delta variant and is causing breakthrough infections in individuals with two booster vaccinations. While the magnitude of morbidity and lethality is lower in Omicron, the infection rate and global spread are rapid. Using a specific IgG multipanel-ELISA with the spike protein’s receptor-binding domain (RBD) from recombinant Alpha, Gamma, Delta, and Omicron variants, sera from health-care workers from the Medical University of Vienna were tested pre-pandemic and post-vaccination (BNT162b2; ChAdOx1 nCoV-19). The cohort was continuously monitored by SARS-CoV-2 testing and commercial nucleocapsid IgG ELISA. RBD IgG ELISA showed significantly lower reactivity against the Omicron-RBD compared to the Alpha variant in all individuals (p < 0.001). IgG levels were independent of sex, but were significantly higher in BNT162b2 recipients <45 years of age for Alpha, Gamma, and Delta (p < 0.001; p = 0.040; p = 0.004, respectively). Pre-pandemic cross-reactive anti-Omicron IgG was detected in 31 individuals and was increased 8.78-fold after vaccination, regardless of vaccine type. The low anti-RBD Omicron IgG level could explain the breakthrough infections and their presence could also contribute to a milder COVID-19 course by cross-reactivity and broadening the adaptive immunity.

Trial registration: ClinicalTrials.gov NCT04347694.

Keywords: COVID-19; Omicron; SARS-CoV-2; cross-reactive antibodies; receptor-binding domain (RBD); variants of concern.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of analyzed sera and vaccination status.
Figure 2
Figure 2
Alignment of the RBD part of the spike protein of SARS-CoV-2, with amino acid changes indicated in yellow when comparing variants Gamma, Delta, and Omicron with Alpha.
Figure 3
Figure 3
Age distribution of vaccinees and anti-RBD IgG levels against SARS-CoV-2 variants. (A) Age distribution of participants receiving ChAdOx1 nCoV-19 (Oxford/AstraZeneca) or BNT162b2 (Pfizer); (B) Anti-RBD-domain IgG levels detected against the variants Alpha, Gamma, Delta, and Omicron after vaccination regardless of vaccine type; **** p < 0.0001, hyphenated line represents the test cut-off.
Figure 4
Figure 4
Intervariant differences of RBD-specific IgG of ChAdOx1 nCoV-19 (Oxford/AstraZeneca) recipients compared with BNT162b2 (Pfizer). Individuals who tested positive in the nucleocapsid ELISA and were classified as convalescent are marked in bright red. (*** p < 0.001).
Figure 5
Figure 5
Gender dependence of RBD variant–specific IgG induction following vaccination with either ChAdOx1 nCoV-19 (Panel A) or BNT162b2 (Panel B).
Figure 6
Figure 6
Age dependence of anti-RBD IgG against variants Alpha, Gamma, Delta, and Omicron. (A) Participants who received the first dose of ChAdOx1 nCoV-19. (B) Participants who received the booster dose of BNT162b2; * p < 0.05; ** p < 0.01; *** p < 0.001.
Figure 7
Figure 7
Cross-reactive IgG antibody levels could be found in several pre-pandemic sera but increased significantly after vaccination. (A) Anti-Omicron IgG increasing from the pre-pandemic status upon vaccination with BNT162b2 (Pfizer) or ChAdOx1 nCoV-19 (Oxford/AstraZeneca) vaccine and/or having undergone mild-to-moderate COVID-19 in healthcare workers. (B) Anti-Omicron-RBD IgG increase from pre-pandemic levels, exhibiting cross-reactivity and increase following vaccination with the BNT162b2 or ChAdOx1 nCoV-19 vaccines. For paired samples, Wilcoxon test was applied; **** p < 0.0001.

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