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. 2023 Mar;128:166-175.
doi: 10.1016/j.ijid.2022.12.034. Epub 2022 Dec 30.

Heterologous prime-boost immunization with ChAdOx1-S and BNT162b2: reactogenicity and immunogenicity in a prospective cohort study

Niko Kohmer  1 , Shivana Stein  2 , Barbara Schenk  2 , Katharina Grikscheit  2 , Melinda Metzler  2 , Holger F Rabenau  2 , Marek Widera  2 , Eva Herrmann  3 , Sabine Wicker  4 , Sandra Ciesek  5
Affiliations
Free PMC article

Heterologous prime-boost immunization with ChAdOx1-S and BNT162b2: reactogenicity and immunogenicity in a prospective cohort study

Niko Kohmer et al. Int J Infect Dis. 2023 Mar.
Free PMC article

Abstract

Objectives: Regarding reactogenicity and immunogenicity, heterologous COVID-19 vaccination regimens are considered as an alternative to conventional immunization schemes.

Methods: Individuals receiving either heterologous (ChAdOx1-S [AstraZeneca, Cambridge, UK]/BNT162b2 [Pfizer-BioNTech, Mainz, Germany]; n = 306) or homologous (messenger RNA [mRNA]-1273 [Moderna, Cambridge, Massachusetts, USA]; n = 139) vaccination were asked to participate when receiving their second dose. Reactogenicity was assessed after 1 month, immunogenicity after 1, 3, and/or 6 months, including a third dose, through SARS-CoV-2 antispike immunoglobulin G, surrogate virus neutralization test, and a plaque reduction neutralization test against the Delta (B.1.167.2) and Omicron (B.1.1.529; BA.1) variants of concern.

Results: The overall reactogenicity was lower after heterologous vaccination. In both cohorts, SARS-CoV-2 antispike immunoglobulin G concentrations waned over time with the heterologous vaccination demonstrating higher neutralizing activity than homologous mRNA vaccination after 3 months to low neutralizing levels in the Delta plaque reduction neutralization test after 6 months. At this point, 3.2% of the heterologous and 11.4% of the homologous cohort yielded low neutralizing activity against Omicron. After a third dose of an mRNA vaccine, ≥99% of vaccinees demonstrated positive neutralizing activity against Delta. Depending on the vaccination scheme and against Omicron, 60% to 87.5% of vaccinees demonstrated positive neutralizing activity.

Conclusion: ChAdOx1-S/BNT162b2 vaccination demonstrated an acceptable reactogenicity and immunogenicity profile. A third dose of an mRNA vaccine is necessary to maintain neutralizing activity against SARS-CoV-2. However, variants of concern-adapted versions of the vaccines would be desirable.

Keywords: BNT162b2; ChAdOx1-S; Heterologous prime-boost; Immunogenicity; Reactogenicity.

Conflict of interest statement

Declaration of competing interest SC received honorarium for serving on a clinical advisory board for BioNTech. All other authors declare no competing interests.

Figures

Figure 1
Figure 1
Study design. AZ, ChAdOx1-S; BNT, BNT162b2; Delta, B.1.617.2; Ig, immunoglobulin; N antibody(ies), SARS-CoV-2 anti-Nucleocapsid IgG; Omicron, B.1.1.529; PCR, polymerase chain reaction; PRNT, cell culture-based plaque reduction neutralization test; S1 antibodies, SARS-CoV-2 antispike IgG antibodies; sVNT, surrogate virus neutralization test. *About 12 weeks distance according to heterologous vaccination scheme **About 4 weeks distance according to homologous vaccination scheme ***For one participant not enough sample volume for the assay ****For one participant not enough sample volume for the cell culture-based neutralization assay against SARS-CoV-2 Omicron VOC
Figure 2
Figure 2
Proportions (%) and number of subjectively reported symptoms after receiving the second dose according to the heterologous or homologous vaccination scheme grouped by severity. AZ, ChAdOx1-S; BNT, BNT162b2.
Figure 3
Figure 3
Levels of SARS-CoV-2 antispike IgG in BAU/ml and median on the day of receiving the second dose and 1, 3 and 6 months after either heterologous or homologous basic vaccination (without a history of infection or having received a third dose). The cutoff to positivity is shown as dotted horizontal line. P-values of an unpaired two-tailed t-test between both cohorts are shown for the follow-up data. AZ, ChAdOx1-S; BAU, binding antibody units; BNT, BNT162b2; Ig, immunoglobulin.
Figure 4
Figure 4
Levels of ACE2-RBD binding inhibition and mean are shown for participants of the 1 month (a) and/or 3 months (b) follow-up visit after heterologous or homologous second dose, including median, 95% confidence interval and P-value of a conducted Mann-Whitney U test between both cohorts. The cutoff to positivity is shown as dotted horizontal line. ACE2, angiotensin-converting enzyme 2; AZ, ChAdOx1-S; BNT, BNT162b2; ns, not significant; RBD, receptor binding domain.
Figure 5
Figure 5
Results of a PRNT against the Delta (B.1.617.2) VOC conducted for participants of the 3 (a) and 6 (b) months follow-up visit after second dose (not having received a third dose), including median, 95% confidence interval of titers and the P-value of a conducted Mann-Whitney U test. Dotted lines indicate cutoff to positivity. AZ, ChAdOx1-S; BNT, BNT162b2; neg, negative; PRNT, plaque reduction neutralization test.
Figure 6
Figure 6
Results of the PRNT regarding the serum neutralization activity of individuals 2 weeks after having received either a third dose of BNT or Moderna including median and 95% confidence interval, significant differences (P-values) and cutoff to positivity (dotted line). AZ, ChAdOx1-S; BNT, BNT162b2; ns, not significant; neg, negative; PRNT, plaque reduction neutralization test.
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