Comparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens

Abstract

Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.

Cellular and humoral immunity towards parental SARS-CoV-2 and variants of concern after two doses of the NVX-CoV2373-vaccine in comparison to homologous BNT162b and mRNA1273 regimens

“…This observational study included 22 healthy immunocompetent individuals, who received the NVX-CoV2373-vaccine as a standard two-dose regimen as per German recommendations [2]. Individuals after dual vaccination with BNT162b2 (n=22) and mRNA-1273 (n=22) matched for age and gender served as controls and were derived in part from convenience cohorts as described before [8, 9] (table 1). All individuals had no known history of SARS-CoV-2 infection and were negative for nucleocapsid-specific IgG.…”

“…Lower CD4 T-cell levels were associated with a significantly lower expression of CTLA-4 and a lower percentage of multifunctional cells. We have previously shown that the phenotypical and functional profile of antigen-specific T cells correlated with antigen-load during active infections [15, 16] or vaccination [8, 9, 17] to counteract excessive T-cell proliferation or immunopathology. Therefore, the phenotypical and functional differences may indicate a lower extent of antigen encounter during the induction phase in NVX-CoV2373-vaccinated individuals.…”

“…In addition, individuals after dual dose vaccination with BNT162b2 and mRNA-1273 matched for age and sex were chosen as control groups. Their data and frozen plasma samples were in part derived from previous observational studies [8, 9]. The time interval between the first and the second vaccination (3 weeks for NVX-CoV2373, 3-6 weeks for mRNA regimens) was based on recommendations [2, 35] and not determined by the study.…”

“…Future effectiveness studies should determine whether the differences in CD4 T-cell levels and functionality and the relative lack of vaccine-induced CD8 T cells may reveal differences between vaccine regimens regarding disease severity upon breakthrough infection. Moreover, it will be interesting to study whether heterologous boosting with mRNA vaccines will induce specific CD8 T cells as was shown for heterologous mRNA-boosting after vector-vaccination [8,9,[22][23][24][25]. Regarding neutralizing activity, a third booster dose after NVX-CoV2373 may seem equally valuable to improve protection as has been shown for other primary vaccine regimens [26][27][28].…”

“…The immunogenicity of the two mRNA vaccines has been extensively characterized in real world settings, and both vaccines induce strong antibody and T-cell responses [8,9]. Likewise, the phase 1-2 trial of the NVX-CoV2373 vaccine or a recent phase III trial has shown induction of high antibody titers [10,11], and first data on neutralizing activity towards SARS-CoV-2 variants of concern (VOCs) from participants of the pivotal trial 3-4 months after the second dose became available recently [12][13][14].…”