Immunogenicity and Durability of Antibody Responses to Homologous and Heterologous Vaccinations with BNT162b2 and ChAdOx1 Vaccines for COVID-19

Abstract

During the COVID-19 pandemic, vaccines were developed based on various platform technologies and were approved for emergency use. However, the comparative analysis of immunogenicity and durability of vaccine-induced antibody responses depending on vaccine platforms or vaccination regimens has not been thoroughly examined for mRNA- or viral vector-based vaccines. In this study, we assessed spike-binding IgG levels and neutralizing capacity in 66 vaccinated individuals prime-boost immunized either by homologous (BNT162b2-BNT162b2 or ChAdOx1-ChAdOx1) or heterologous (ChAdOx1-BNT162b2) vaccination for six months after the first vaccination. Despite the discrepancy in intervals for the prime-boost vaccination regimen of different COVID-19 vaccines, we found stronger induction and relatively rapid waning of antibody responses by homologous vaccination of the mRNA vaccine, while weaker boost effect and stable maintenance of humoral immune responses were observed in the viral vector vaccine group over 6 months. Heterologous vaccination with ChAdOx1 and BNT162b2 resulted in an effective boost effect with the highest remaining antibody responses at six months post-primary vaccination.

Keywords: BNT162b2; COVID-19; ChAdOx1; SARS-CoV-2; antibody; vaccine.

Figure 1

Study design and peak antibody responses. (A) Schematic presentation of experimental schedule. The individuals were vaccinated with BNT162b2 and ChAdOx1 followed by the second dose in either homologous (BNT162b2-BNT162b2, ChAdOx1-ChAdOx1) or heterologous (ChAdOx1-BNT162b2) manner. The groups and time points for collecting blood specimens are depicted in the figure. (B) Levels of anti-nucleocapsid antibody in plasma specimens. (C,D) Levels of SARS-CoV-2 spike-binding antibody (C) and neutralizing antibody to SARS-CoV-2 (D) were measured from plasma specimens at 3–4 weeks post-primary vaccination by ELISA and microneutralization assay, respectively. (E,F) Titers of SARS-CoV-2 spike-binding antibody (E) and neutralizing antibody (F) were assessed three weeks after the boost shot. * p < 0.05, ** p < 0.01, and *** p < 0.001.

Figure 2

Kinetic changes and maintenance of spike-binding IgGs. Vaccine-induced spike-binding antibody titers were longitudinally monitored in three vaccinated groups. (A–C) Kinetics of SARS-CoV-2 spike-specific IgG levels in the BNT-BNT (A), ChAd-ChAd (B), and ChAd-BNT (C) groups. (D) Titers of anti-spike IgGs in the three groups approximately six months after primary immunization. (E) Boosting effect of secondary vaccination depicted by the fold increase in anti-spike IgG levels. (F) Fold change in anti-spike IgG contractions for three months after the second shot. (G) Fold changes in anti-spike IgG titers from three weeks post-primary immunization to the last monitoring period (six months). * p < 0.05, ** p < 0.01, and **** p < 0.0001.

Figure 3

Kinetic changes and maintenance of SARS-CoV-2 neutralizing antibodies. Plasma-neutralizing antibody titers against SARS-CoV-2 were assessed longitudinally in vaccinated individuals. (A–C) Kinetic changes in neutralizing antibody titers in the BNT-BNT (A), ChAd-ChAd (B), and ChAd-BNT (C) groups. (D) Neutralizing capacities in the three groups of vaccinees at approximately six months after primary immunization. (E) Boosting effect of secondary vaccination is displayed by the fold increase in neutralizing antibody levels. (F) Fold change in neutralizing antibodies for 3 months after the second shot. (G) Fold changes in neutralizing antibody titers from three weeks to approximately six months after the primary immunization. ** p < 0.01, and *** p < 0.001.

Figure 3

Kinetic changes and maintenance of SARS-CoV-2 neutralizing antibodies. Plasma-neutralizing antibody titers against SARS-CoV-2 were assessed longitudinally in vaccinated individuals. (A–C) Kinetic changes in neutralizing antibody titers in the BNT-BNT (A), ChAd-ChAd (B), and ChAd-BNT (C) groups. (D) Neutralizing capacities in the three groups of vaccinees at approximately six months after primary immunization. (E) Boosting effect of secondary vaccination is displayed by the fold increase in neutralizing antibody levels. (F) Fold change in neutralizing antibodies for 3 months after the second shot. (G) Fold changes in neutralizing antibody titers from three weeks to approximately six months after the primary immunization. ** p < 0.01, and *** p < 0.001.