Higher SARS-CoV-2 Spike Binding Antibody Levels and Neutralization Capacity 6 Months after Heterologous Vaccination with AZD1222 and BNT162b2

Abstract

Within a year after the emergence of SARS-CoV-2, several vaccines had been developed, clinically evaluated, proven to be efficacious in preventing symptomatic disease, and licensed for global use. The remaining questions about the vaccines concern the duration of protection offered by vaccination and its efficacy against variants of concern. Therefore, we set out to analyze the humoral and cellular immune responses 6 months into homologous and heterologous prime-boost vaccinations. We recruited 190 health care workers and measured their anti-spike IgG levels, their neutralizing capacities against the Wuhan-Hu-1 strain and the Delta variant using a surrogate viral neutralization test, and their IFNγ-responses towards SARS-CoV-2-derived spike peptides. We here show that IFNγ secretion in response to peptide stimulation was significantly enhanced in all three vaccination groups and comparable in magnitude. In contrast, the heterologous prime-boost regimen using AZD1222 and BNT162b2 yielded the highest anti-spike IgG levels, which were 3–4.5 times more than the levels resulting from homologous AZD1222 and BNT162b2 vaccination, respectively. Likewise, the neutralizing capacity against both the wild type as well as the Delta receptor binding domains was significantly higher following the heterologous prime-boost regimen. In conclusion, our results suggest that mixing different SARS-CoV-2 vaccines might lead to more efficacious and longer-lasting humoral protection against breakthrough infections.

High Incidence of SARS-CoV-2 Variant of Concern Breakthrough Infections Despite Residual Humoral and Cellular Immunity Induced by BNT162b2 Vaccination in Healthcare Workers: A Long-Term Follow-Up Study in Belgium

“…Serological findings of this cohort were comparable with those described by other groups that studied serology up to 32 weeks after receiving the BNT162b2 vaccine [44][45][46][47][48][49][50][51][52]. Of note, many of these studies monitored vaccine-induced antibody responses in either patients with multiple pathologies (e.g., multiple sclerosis, hemodialysis) [44][45][46]53,54], SARS-CoV-2 convalescent patients [55][56][57] or between patients receiving one, two or three doses of the BNT162b2 vaccine [57,58].…”

An Evaluation of Serological Tests to Determine Postvaccinal Immunity to SARS-CoV-2 by mRNA Vaccines

“…These data are consistent with those observed in our and other studies that studied serology up to 32 weeks after receiving mRNA vaccines [36][37][38]. Other studies have reported the clinical performance of the Abbott trial [31,35,39] with results similar to ours.…”

Vaccine-Induced T-Cell and Antibody Responses at 12 Months after Full Vaccination Differ with Respect to Omicron Recognition

“…While a two-dose vaccination with any of the above mentioned vaccines elicited strong antibody responses even in low responders, we and others were able to demonstrate that a heterologous prime boost regimen combining AZD1222 with any of the mRNA vaccines not only elicited a significantly higher number of antibodies, but also improved neutralizing capacity [3,4]. On the other hand, spike protein specific antibodies decreased over time with an estimated half-life of approximately 55 days and this decline in humoral protection seemed independent of the vaccine [5,6].…”