Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination

Abstract

Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.

A ‘mix and match’ approach to SARS-CoV-2 vaccination

“…In addition, the participants dosed with ChAd-mRNA demonstrate a greater number of circulating spike protein-specific CD4 + and CD8 + T cells, as well as cytokine-producing T cells, than that of participants dosed with ChAd-ChAd. Schmidt et al further demonstrate comparable multifunctional, spike proteinspecific CD4 + T cell responses but greater CD8 + T cell responses in the ChAd-mRNA group 3 . A third study, published recently in Lancet, provides additional evidence that the heterologous ChAd-mRNA vaccine approach is well tolerated and stimulates a robust IgG and neutralizing-antibody response 4 .…”

“…These neutralizing titers were approximately threefold higher than those in serum from the groups dosed with BNT-BNT (albeit with differing intervals between dose 1 and dose 2), with higher titers of the IgG and IgA subclasses. Similarly, Schmidt et al show significantly higher titers of IgG antibodies directed against the SARS-CoV-2 spike protein and receptor-binding domain after ChAd-mRNA (either BNT162b2 or mRNA-1273) or mRNA-mRNA vaccination than after homologous ChAd-ChAd vaccination 3 . In addition, the participants dosed with ChAd-mRNA demonstrate a greater number of circulating spike protein-specific CD4 + and CD8 + T cells, as well as cytokine-producing T cells, than that of participants dosed with ChAd-ChAd.…”

“…In this issue of Nature Medicine, studies by Barros-Martins et al 2 and Schmidt et al 3 capitalize on the ad hoc heterologous primeboost vaccination that resulted from the halting of vaccination with ChAd in several European countries, which left partially vaccinated people the option of completing their vaccinations with an mRNA vaccine (BNT162b2 (BNT), from Pfizer-BioNTech); or mRNA-1273, from Moderna). Barros-Martins et al report that, compared with results obtained by homologous ChAd-ChAd dosing, the ChAd-BNT dosing strategy resulted in significantly greater immunoglobulin G (IgG) and IgA immune responses directed against the SARS-CoV-2 spike protein and robust, 20-to >60-fold greater titers of neutralizing antibody against the Alpha (B.1.1.7), Beta (B.1.351) and Gamma (P.1) SARS-CoV-2 variants of concern 2 .…”

An Immunogenicity Report for the Comparison between Heterologous and Homologous Prime-Boost Schedules with ChAdOx1-S and BNT162b2 Vaccines

“…Previous studies have shown that a second vaccination with BNT was associated with increased anti-spike IgG levels for ChAdOx1-S-primed peopled compared to those having only one ChAdOx1-S dose [10][11][12]. However, contradictory anti-spike IgG levels were observed between participants who received homologous BNT/BNT vaccines or heterologous ChAdOx1-S/BNT vaccines with similar rates [10,13] and higher rates for heterologous ChAdOx1-S/BNT vaccines [9,14,15]. Nevertheless, no evidence of immune response outcomes with heterologous vaccine strategies is clearly available to date for the COVID-19 pandemic [16].…”

“…Nevertheless, on 15 March 2021, numerous European countries stopped ChAdOx1-S vaccine use as a precaution to investigate the death of a few dozen patients developing blood clots associated with deep vein thrombosis (DVT) [3]. In Europe, on 15 March 2021, only 30 suspect cases of DVT had been observed [4]. However, on 22 March 2021, the ChAdOx1-S vaccine campaign resumed in many countries, including France [5].…”