The anti-SARS-CoV-2 immunoglobulin G levels and neutralising capacities against alpha and delta virus variants of concern achieved after initial immunisation with vector vaccine followed by mRNA vaccine boost are comparable to those after double immunisation with mRNA vaccines

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.

Kinetics and persistence of anti‐SARS‐CoV‐2 neutralisation and antibodies after BNT162b2 vaccination in a Swiss cohort

“…24 Indeed, maturation of the IgG antibodies after infection and booster vaccination have been demonstrated by measuring the anti-SARS-CoV-2 IgG avidity. 25,26 In addition to an earlier onset after vaccination, we found that peak neutralisation titres in convalescent study subjects were much higher than in naïve subjects. Additionally, after approximately 60 days, the neutralising antibodies of naïve individuals decreased, whereas for convalescent patients they remained high, suggesting, therefore, a more robust and long-lasting protection in the latter cohort, as it has been implicated previously.…”