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.

Immune Persistence and Safety After SARS-CoV-2 BNT162b1 mRNA Vaccination in Chinese Adults: A Randomized, Placebo-Controlled, Double-Blind Phase 1 Trial

“…In this trial, there was a gradual decline in GMTs of neutralizing, anti-S1 IgG and anti-RBD antibodies, though humoral immune responses were observed through 6 months of follow-up. These results are comparable to other SARS-CoV-2 vaccines (including BNT162b2), which have also demonstrated waning antibody titers over the 6 months post-vaccination [19][20][21][22]. As T-cell response is thought to play a role in preventing reinfection, particularly in the context of waning antibody titers, these reduced titers may not correspond to a less efficacious vaccine [23].…”

“…Antibody titers at month 3 (day 85) and month 6 (day 184) after the first dose are shown in Fig. 1 [11][12][13][14][15][16][17][18][19][20][21][22][23][24] and 27 (95% CI 20-37) at month 6, respectively. In older participants, GMTs of nAb at month 6 declined from 80 (95% CI 49-130) and 160 (95% CI 97-265) to 10 (95% CI 7-14) and 21 (95% CI 13-32), respectively.…”

Correlates of protection, viral load trajectories and symptoms in BA.1, BA.1.1 and BA.2 breakthrough infections in triple vaccinated healthcare workers

“…We have previously reported increased cross-neutralization potency against SARS-CoV-2 variants following primary vaccination with two doses BNT or heterologous ChAd followed by BNT as compared to two doses of ChAd [23]. Using blood samples taken before (figure 2A) and five weeks after (figure 2B) MOD booster vaccination, we found comparable post booster anti-WT spike IgG (figure 2B), anti-WT RBD IgG (figure S1A), cross-reactive IgG capable of binding omicron BA.1 spike (figure S1B) and RBD (figure S1C) and neutralizing titers against both WT (figure S1D) and omicron BA.1 (figure S1E).…”

Dynamics of humoral and cellular immune responses after homologous and heterologous SARS-CoV-2 vaccination with ChAdOx1 nCoV-19 and BNT162b2

“… 13 For heterologous vaccination regimens, however, follow-up data on how long B- and T-cell immunity persists are limited. 14 , 15 This particularly applies to the immune response against newly emerged SARS-CoV-2 variants of concern (VoC) such as the Delta or Omicron mutant. 8 Currently, it therefore remains unclear how the heterologous combination of ChAd and mRNA vaccination compares to homologous mRNA or ChAd vaccination in terms of persistence of humoral and cellular immunity.…”