Duration of SARS-CoV-2 Immune Responses Up to Six Months Following Homologous or Heterologous Primary Immunization with ChAdOx1 nCoV-19 and BNT162b2 mRNA Vaccines

Abstract

Heterologous primary immunization against SARS-CoV-2 is part of applied recommendations. However, little is known about duration of immune responses after heterologous vaccine regimens. To evaluate duration of immune responses after primary vaccination with homologous adeno-vectored ChAdOx1 nCoV-19 vaccine (ChAd) or heterologous ChAd/BNT162b2 mRNA vaccine (BNT), anti-spike-IgG and SARS-CoV-2 VOC-neutralizing antibody responses were measured in 354 healthcare workers (HCW) at 2 weeks, 3 months, 5 months and 6 months after the second vaccine dose. T-cell responses were investigated using a whole blood interferon gamma (IFN-γ) release assay 2 weeks and 3 months post second vaccine dose. Two hundred and ten HCW immunized with homologous BNT were enrolled for comparison of antibody responses. In study participants naïve to SARS-CoV-2 prior to vaccination, heterologous ChAd/BNT resulted in 6-fold higher peak anti-spike IgG antibody titers compared to homologous ChAd vaccination. The half-life of antibody titers was 3.1 months (95% CI 2.8-3.6) following homologous ChAd vaccination and 1.9 months (95% CI 1.7-2.1) after heterologous vaccination, reducing the GMT difference between the groups to 3-fold 6 months post vaccination. Peak T-cell responses were stronger in ChAd/BNT vaccinees, but no significant difference was observed 3 months post vaccination. SARS-CoV-2 infection prior to vaccination resulted in substantially higher peak GMTs and IFN-γ levels and enhanced SARS-CoV-2 specific antibody and T cell responses over time. Heterologous primary SARS-CoV-2 immunization with ChAd and BNT elicits a stronger initial immune response compared to homologous vaccination with ChAd. However, although the differences in humoral responses remain over 6 months, the difference in SARS-CoV-2 specific T cell responses are no longer significant three months after vaccination.

Keywords: COVID-19; SARS-CoV-2; SARS-CoV-2 vaccination; T-cells; antibodies; duration; heterologous; humoral response; immune response; immunity; immunology.

Figure 1

Change in anti-spike IgG titers over 6 months following vaccination. Circles represent individual values, lines represent geometric mean titer with 95% CI in (A) participants SARS-CoV-2 naïve prior to vaccination and (B) participants SARS-CoV-2 recovered prior to vaccination. ChAd; ChAdOx1 nCoV-19 vaccine, BNT; BNT162b2 mRNA vaccine.

Figure 2

Surrogate virus neutralization GMT 3 months post heterologous ChAd/BNT (n = 149, median time to sampling 90 days (range 82–105)) and homologous ChAd/ChAd (n = 56, median time to sampling 98 days (range 77–105)) primary vaccination in SARS-CoV-2 naïve participants. Samples 3 months post homologous BNT/BNT (n = 210, median time to sampling 87 days (range 75–104)) are presented for reference. Dotted line (wt) represents cut-off value set by the manufacturer. * p = 0.0252, **** p < 0.001, ns; not significant. Ab; antibodies, WT; wild type, AU; Arbitrary Units, ChAd; ChAdOx1 nCoV-19 vaccine, BNT; BNT162b2 mRNA vaccine.

Figure 3

Concentration of background-adjusted interferon-gamma (IFN-γ) levels after whole-blood stimulation with 16 SARS-CoV-2 specific peptides in serial sampling at 2 weeks (14–21 days) and 3 months (75–105 days) after vaccine in (A) SARS-CoV-2 naïve (ChAd/BNT n = 92, ChAd/ChAd n = 48) and (B) SARS-CoV-2 recovered (ChAd/BNT n = 25, ChAd/ChAd n = 25) participants. IFN-γ was measured by ELISA in the supernatant. Transparent circles represent individual samples, filled circles represent geometric mean with 95% CI. IFN-γ; Interferon-γ, ChAd; ChAdOx1 nCoV-19 vaccine, BNT; BNT162b2 mRNA vaccine.