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

• Published in: International journal of infectious diseases Vol. 128; pp. 166 - 175
• Main Authors: Kohmer, Niko, Stein, Shivana, Schenk, Barbara, Grikscheit, Katharina, Metzler, Melinda, Rabenau, Holger F., Widera, Marek, Herrmann, Eva, Wicker, Sabine, Ciesek, Sandra
• Format: Journal Article
• Language: English
• Published: Canada Elsevier Ltd 01-03-2023; Elsevier
• Subjects: Antibodies, Neutralizing; Antibodies, Viral; BNT162 Vaccine; BNT162b2; ChAdOx1 nCoV-19; ChAdOx1-S; COVID-19; COVID-19 Vaccines; Heterologous prime-boost; Humans; Immunization; Immunogenicity; Immunoglobulin G; Prospective Studies; Reactogenicity; RNA, Messenger; SARS-CoV-2; Vaccination; BNT162b2; ChAdOx1-S; Immunogenicity; Heterologous prime-boost; Reactogenicity
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2022.12.034

•Heterologous vaccination showed an acceptable reactogenicity and immunogenicity.•Heterologous (ChAdOx1-S/BNT162b2) vaccination temporarily led to higher neutralizing activity than homologous messenger RNA vaccination.•A third dose of a messenger RNA vaccine maintains neutralizing activity against SARS-CoV-2.•SARS-CoV-2 variant of concern-adapted versions of the vaccines would be desirable.
Regarding reactogenicity and immunogenicity, heterologous COVID-19 vaccination regimens are considered as an alternative to conventional immunization schemes.
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.
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.
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.