Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study

Abstract

Background Heterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation. Methods This is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay.

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

“…Currently approved vector and mRNA vaccination strategies against SARS-CoV-2 consider only homologous vaccination. However, recent studies indicate a better humoral and cellular immune response after heterologous prime-boost vaccination in healthy individuals 16,[18][19][20][21] . In our study, no significant advantage for either the homologous or heterologous vaccination strategy was found: the primary outcome showed a 10% higher seroconversion rate for mRNA (homologous) versus vector (heterologous) vaccination.…”

Long-term immunogenicity of BNT162b2 vaccination in the elderly and in younger health care workers

“…However, the durability of vaccine-induced immunity in the elderly is currently unknown. Following up on a previous analysis, we describe interim results of a prospective cohort study comparing immune responses in a cohort of vaccinated elderly persons to those in healthcare workers (HCW) 4,5 , measured six months after first immunisation with BNT162b2. 1).…”

“…Blood samples were tested for anti-SARS-CoV-2 antibodies, neutralizing capacity, and T cell reactivity as previously described 5 . In brief, SARS-CoV-2 specific antibodies were quantified using the commercially available SeraSpot® Anti-SARS-CoV-2 IgG microarray-based immunoassay including nucleocapsid and spike as antigens (Seramun Diagnostica GmbH, https://www.seramun.com), allowing for differentiation between infection and vaccineinduced immune responses.…”

“…Study participants were recruited in the EICOV, COVIMMUNIZE, and COVIM studies, three prospective cohort studies conducted under the auspices of Charité -Universitätsmedizin Berlin, Germany, in accordance with the Declaration of Helsinki and Good Clinical Practice. 4,5 EICOV and COVIMMUNIZE studies were approved by the local ethics committee of Charité -Universitätsmedizin Berlin (EA4/244/20, EA4/245/20), and COVIM was approved by the Federal Institute for Vaccines and Biomedicines (Paul Ehrlich Institute) and by the ethics committee of the state of Berlin (EudraCT-2021-001512-28). Written informed consent was obtained by all participants, according to local and national regulations.…”

Anti-COVID-19 Vaccination in Patients with Autoimmune-Autoinflammatory Disorders and Primary/Secondary Immunodeficiencies: The Position of the Task Force on Behalf of the Italian Immunological Societies

“…However, a preliminary study on 830 subjects, in whom the adverse effects (AEs) were analyzed following either two doses of the same vaccine, Pfizer or AstraZeneca, or two doses of different vaccine types, the first Pfizer and the second AstraZeneca, or vice versa, showed a higher prevalence of AEs in the group receiving different vaccine types than the group receiving the same type [43]. The higher prevalence of AEs in patients receiving heterologous vaccine doses was not confirmed in two smaller studies, the first on 326 healthcare workers [44] and the other on 26 subjects [45]. In the latter study, cellular and humoral immunogenicity were explored and the results confirmed the data on the high stimulation of the immune system by the heterologous immunization already observed in the Spanish study, even towards the variants of concern.…”