Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity

Abstract

Background Heterologous prime-boost schedules with vector- and mRNA-based COVID-19 vaccines are already administered, but immunological responses and elicited protection have not been reported. Methods We here analyzed a cohort of 26 individuals aged 25-46 (median 30.5) years that received a ChAdOx1 nCoV-2019 prime followed by a BNT162b2 boost after an 8-week interval for reactogenicity, antibody responses and T cell reactivity. Results Self-reported solicited symptoms after ChAdOx1 nCoV-2019 prime were in line with previous reports and less severe after the BNT162b2 boost. Antibody titers increased significantly over time resulting in strong neutralization titers 2 weeks after the BNT162b2 boost. Neutralizing activity against the prevalent strain B.1.1.7 was 3.9-fold higher than in individuals receiving homologous BNT162b2 vaccination, only 2-fold reduced for variant of concern B.1.351, and similar for variant B.1.617. In addition, CD4+ and CD8+ T cells reacted to SARS-CoV-2 spike peptide stimulus 2 weeks after the full vaccination. Conclusions The heterologous ChAdOx1 nCoV-2019 / BNT162b2 prime-boost vaccination regimen is not associated with serious adverse events and results in a potent humoral immune response and elicits T cell reactivity. Variants of concern B.1.1.7, B.1.351 and B.1.617 are potently neutralized by sera of all participants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations.

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

“…The data presented by us on the humoral immune response after heterologous SARS-CoV-2 vaccination are consistent with the few available clinical studies [16,18,17,19]. A recent preprint reports significant higher anti-S-antibody titres in a group of 26 individuals who first received an AZD1222 vaccination followed by re-vaccination with BNT162b2 compared to 14 individuals that were vaccinated twice with BNT162b2.…”

“…In the first quarter of this year, however, only a few animal experimental data were available on the immunological outcome of the proposed heterologous vaccination scheme [13, 14]. Several studies have now appeared on the immunogenicity of the heterologous vaccination scheme in humans [16, 21, 17-20].…”

“…First results indicated a higher prevalence of shortlived side effects following the heterologous boost dose compared to the homologous counterpart [15]. Only a few and mostly preliminary results have so far been published for the immunogenicity of the AZD1222 / mRNA vaccine regimen [16][17][18][19].…”

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.…”

Single-Dose SARS-CoV-2 Vaccination With BNT162b2 and AZD1222 Induce Disparate Th1 Responses and IgA Production

“…Another limitation is the lack of assaying neutralizing SARS-CoV-2 specific antibodies. However, previous studies have already demonstrated that total spike-binding Ig titers strongly correlate with the amounts of neutralizing antibodies and are therefore a suitable measure for humoral protection from SARS-CoV-2 infection 5,[40][41][42] . In summary, we consider the description of disparate vaccine effects on the immediate immune response the strength of our study and we believe that our results will be of use for further optimization of vaccination strategies.…”