COVID-19 vaccine type-dependent differences in immunogenicity and inflammatory response: BNT162b2 and ChAdOx1 nCoV-19

Abstract

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1β levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.

Keywords: COVID-19; cytokine; immunogenicity; reactogenicity; vaccine.

Figure 1

Diagram showing the study flow.

Figure 2

Comparison of antibody response between the ChAdOx1 nCoV-19 and BNT162b2 groups: (A) anti-S antibodies (mean ± standard deviation, U/mL): ^*0 in ChAdOx1 and 0 in BNT162b2; ^†50.0 ± 66.3 in ChAdOx1 and 101.5 ± 136.6 in BNT162b2; ^‡1398.9 ± 1503.9 in ChAdOx1 and 2049.5 ± 1417.4 in BNT162b2; ^§589.9 ± 679.7 in ChAdOx1 and 1171.2 ± 703.4 in BNT162b2 and (B) neutralizing antibodies (mean ± standard deviation): ^*15.1 ± 37.1 in ChAdOx1 and 13.6 ± 10.8 in BNT162b2; ^†293.2 ± 312.4 in ChAdOx1 and 325.7 ± 442.0 in BNT162b2; ^‡642.5 ± 812.1 in ChAdOx1 and 1786.9 ± 1322.2 in BNT162b2; ^§277.8 ± 301.9 in ChAdOx1 and 684.6 ± 806.7 in BNT162b2.

Figure 3

Comparison of antibody response against the wild-type and Delta variant strains between the ChAdOx1 nCoV-19 and BNT162b2 groups. *ChAdOx1 group (mean ± standard deviation): 480.1 ± 404.7 in wild-type virus and 148.3 ± 133.6 in Delta variant strain. †BNT162b2 group (mean ± standard deviation): 1706.1 ± 833.4 in wild-type virus and 487.4 ± 381.9 in Delta variant strain.

Figure 4

Concentration of proinflammatory cytokines before and after the first and second dose of ChAdOx1 nCoV-19 and BNT162b2: (A) IL-1β, (B) IL-6, and (C) TNF-α. Before the first dose (D0), day 3 after the first dose (D1), before the second dose (D2), and day 3 after the second dose (D3). Symbol * within graph is data value along with °.

Figure 5

Comparison of antibody response after the first and second dose in ChAdOx1 nCoV-19 and BNT162b2 recipients with respect to febrile adverse events: (A) anti-S antibodies at 3 weeks after the first dose, (B) anti-S antibodies at 3 weeks after the second dose, (C) anti-S antibodies at 12 weeks after the second dose, (D) neutralizing antibodies at 3 weeks after the first dose, (E) neutralizing antibodies at 3 weeks after the second dose and (F) neutralizing antibodies at 12 weeks after the second dose. □ Vaccine recipients without febrile adverse events. ▪ Vaccine recipients with febrile adverse events. Symbol * within graph is data value along with °.