Heterologous immunisation with vector vaccine as prime followed by mRNA vaccine as boost leads to humoral immune response against SARS-CoV-2, which is comparable to that according to a homologous mRNA vaccination scheme

Abstract

Background: The humoral immune response after primary immunisation with a SARS-CoV-2 vector vaccine (AstraZeneca AZD1222, ChAdOx1 nCoV-19, Vaxzevria) followed by an mRNA vaccine boost (BioNTech, BNT162b2; Moderna, m-1273) was examined and compared with the antibody response after homologous vaccination schemes (AZD1222/AZD1222 or BNT162b2/BNT162b2). Methods: Sera from 59 vaccinees were tested for SARS-CoV-2 immunoglobulin G (IgG) and virus-neutralising antibodies (VNA) with four IgG assays, a surrogate neutralisation test (sVNT) and a Vero cell-based neutralisation test (cVNT) before and after heterologous (n=31 and 42) or homologous booster vaccination (AZD1222/AZD1222, n=8/9; BNT162b2/BNT162b2, n=8/8). The strength of IgG binding to separate SARS-CoV-2 antigens was measured as avidity. Results: After the first vaccination, prevalence of IgGs antibodies directed against (trimeric) SARS-CoV-2 spike (S)- protein and its receptor-binding domain (RBD) varied from 55-95 % (AZD1222) to 100% (BNT162b2), depending on the vaccine used and the SARS-CoV-2 antigen used. The booster vaccination resulted in 100 percent seroconversion and appearance of highly avid IgG as well as VNA against a SARS-CoV-2 variant of concern (alpha; B.1.1.7) used as antigen in the cVNT. The results of the sVNT basically agree with those of our in-house cVNT, but the sVNT seems to overestimate non- and weakly virus-neutralizing titres. The mean IgG and VNA titres were higher after heterologous vaccination compared to the homologous AZD1222 scheme. Conclusions: The heterologous SARS-CoV-2 vaccination leads to a strong antibody response with anti-SARS-CoV-2 IgG and VNA titres at a level comparable to that of a homologous BNT162b2 vaccination scheme. Irrespectively of the chosen immunisation regime, highly avid IgG antibodies can be detected just two weeks after the second vaccine dose indicating the development of a robust humoral immunity.