Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2

Abstract

BackgroundHeterologous vaccinations against SARS-CoV-2 with ChAdOx1 nCoV-19 and a second dose of an mRNA-based vaccine have been shown to be more immunogenic than homologous ChAdOx1 nCoV-19. In the current study, we examined the kinetics of the antibody response to the second dose of three different vaccination regimens (homologous ChAdOx1 nCoV-19 vs. ChAdOx1 nCoV-19 + BNT162b2 or mRNA-1273) against SARS-CoV-2 in a longitudinal manner; whether there are differences in latency or amplitude of the early response and which markers are most suitable to detect these responses.MethodsWe performed assays for anti-S1 IgG and IgA, anti-NCP IgG and a surrogate neutralization assay on serum samples collected from 57 participants on the day of the second vaccination as well as the following seven days.ResultsAll examined vaccination regimens induced detectable antibody responses within the examined time frame. Both heterologous regimens induced responses earlier and with a higher amplitude than homologous ChAdOx1 nCoV-19. Between the heterologous regimens, amplitudes were somewhat higher for ChAdOx1 nCoV-19 + mRNA-1273. There was no difference in latency between the IgG and IgA responses. Increases in the surrogate neutralization assay were the first changes to be detectable for all regimens and the only significant change seen for homologous ChAdOx1 nCoV-19.DiscussionBoth examined heterologous vaccination regimens are superior in immunogenicity, including the latency of the response, to homologous ChAdOx1 nCoV-19. While the IgA response has a shorter latency than the IgG response after the first dose, no such difference was found after the second dose, implying that both responses are driven by separate plasma cell populations. Early and steep increases in surrogate neutralization levels suggest that this might be a more sensitive marker for antibody responses after vaccination against SARS-CoV-2 than absolute levels of anti-S1 IgG.

Differences in Immunogenicity of Three Different Homo- and Heterologous Vaccination Regimens against SARS-CoV-2

“…In addition, a small, but non-negligible number of participants, especially receiving ChAdOx/ChAdOx, did not develop levels of the examined markers considered to be reactive. This is a clear continuation in the results we saw within the first 7 days after the second vaccination [ 14 ], with the exception that after 14 days, we were able to detect significant increases in B- and T-cell responses after a second vaccination with ChAdOx, while we were not able to detect significant increases for most markers within the first 7 days.…”

“…Our data do not support superiority of heterologous vaccination regimens over homologous mRNA-based regimens. Rather, the comparison with the previous study [ 14 ] shows that, if anything, homologous mRNA-based regimens are likely superior to their heterologous counterparts in the induction of anti-S1 IgG and IgA. However, a detailed analysis of different mRNA-based homo- and heterologous regimens is still lacking.…”

“…Drawing on available data, we hypothesized that: In continuation of the trend already seen within the first seven days after the second vaccination, heterologous vaccinations induce an immune response comparable or superior in size to that induced by homologous vaccination with ChAdOx. Among heterologous vaccinations, a second dose of Mod induces a greater immune response than a second dose of BNT (in analogy to the corresponding homologous vaccination regimens [ 13 ] and the trend we have seen within the first seven days [ 14 ]). Age might be a general influencing factor, with older age possibly being associated with weaker immune responses.…”

“…Among heterologous vaccinations, a second dose of Mod induces a greater immune response than a second dose of BNT (in analogy to the corresponding homologous vaccination regimens [ 13 ] and the trend we have seen within the first seven days [ 14 ]).…”

“…In another study, we examined the kinetics of the B-cell response to a second dose of three different vaccines against SARS-CoV-2 in a cohort of participants who had previously received a first dose of ChAdOx. We found that within the first seven days after the second vaccination, a second dose of Mod or BNT elicits earlier and stronger B-cell responses than a second dose of ChAdOx, while a trend showed stronger reactions after a second vaccination with Mod compared to BNT [ 14 ].…”