Immunogenicity of a Heterologous Prime-Boost COVID-19 Vaccination with mRNA and Inactivated Virus Vaccines Compared with Homologous Vaccination Strategy against SARS-CoV-2 Variants

Abstract

The emergence of SARS-CoV-2 variants may impact the effectiveness of vaccines, while heterologous vaccine strategy is considered to provide better protection. The immunogenicity of an mRNA-inactivated virus vaccine against the SARS-CoV-2 wild-type (WT) and variants was evaluated in the study. SARS-CoV-2 naïve adults (n = 123) were recruited and placed in the following groups: BNT162b2, CoronaVac or BNT162b2-CoronaVac (Combo) Group. Blood samples were collected to measure neutralization antibodies (NAb) by a live virus microneutralization assay (vMN) and surrogate NAb test. The day 56 vMN geometric mean titre (GMT) was 26.2 [95% confident interval (CI), [22.3-30.9] for Combo, 136.9 (95% CI, 104.2-179.7) for BNT162b2, and 14.7 (95% CI, 11.6-18.6) for CoronaVac groups. At 6 months post-first dose, the GMT declined to 8.0, 28.8 and 7.1 in the Combo, BNT162b2 and CoronaVac groups, respectively. Three groups showed reduced neutralizing activity against D614G, beta, theta and delta variants. At day 56 GMT (74.6) and month 6 GMT (22.7), the delta variant in the BNT162b2 group was higher than that in the Combo (day 56, 7.4; month 6, 5.5) and CoronaVac groups (day 56, 8.0; month 6, 5) (p < 0.0001). Furthermore, the mean surrogate NAb value on day 56 in the BNT162b2 group was 594.7 AU/mL and higher than 40.5 AU/mL in Combo and 38.8 AU/mL in CoronaVac groups (p < 0.0001). None of the participants developed severe adverse events, and all other adverse events were self-limiting. The Combo vaccination strategy was safe. The overall vaccine immunogenicity at day 56 and 6 months were comparable to the homologous CoronaVac group but inferior to the homologous BNT162b2 group, against both the WT and all variants. Furthermore, the antibody response of vaccines waned at 6 months and thereby, a third dose of the vaccine is needed for these vaccines.

Keywords: COVID-19; heterologous vaccination; neutralizing antibody; variants.

Figure 1

Participant recruitment and research flow diagram.

Figure 2

Comparison of immunogenicity of three vaccination strategies. SARSA-CoV-2 naïve individuals were invited to participate in the vaccination programme. In the Combo group, subjects received one dose of BNT162b2 on day 0 and one dose of CoronaVac on day 28. Then, blood samples were collected on the baseline, day 28, day 56 and month 6. For BNT162b2, subjects recieved two doses of BNT162b2 at the baseline and day 21 respectively and blood was taken at the baseline, day 21, day 56 and month 6. For CoronaVac, Individuals received two doses of CoronaVac vaccine at the baseline and day 28, respectively, and then blood was taken at the baseline, day 28, day 56 and month 6. The live virus microneutralization assay (vMN) was used to determine the level of neutralizing antibodies in serum against (a) wild type, (b) D614G, (c) alpha, (d) beta, (e) theta and (f) delta. BL: baseline; D28: day 28 for Combo and CoronaVac, day 21 for BNT162b2; D56: day 56; M6: month 6. To analyse the difference in immunogenicity between two groups, a post hoc multiple comparison was performed, and a p value was shown on the graph if the value was less than 0.05, which represents a statistically significant difference.