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.

Ruiqi Zhang,Kwok-Yung Yuen,Kwok-Hung Chan,Yujing Fan,Honglin Chen,Ivan Fan-Ngai Hung,Danlei Liu,Ka-Yi Leung,Lu Lu,Pui-Chun Chan,Kelvin Kai-Wang To

doi:10.3390/vaccines10010072

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.

Highlights

Introduction conditions of the Creative CommonsThe ongoing coronavirus disease 2019 (COVID-19) pandemic has lasted more than one and half years and continues to threaten the world
Between May and November 2021, 122 SARS-CoV-2 naïve individuals were invited to the participate in the COVID-19 vaccination programme
Despite an inferior neutralizing antibody response when compared to the homologous BNT162b2, one dose of the CoronaVac vaccine could maintain the immune response induced by the primer dose of BNT162b2 in the Combo group

Summary

Introduction

Introduction conditions of the Creative CommonsThe ongoing coronavirus disease 2019 (COVID-19) pandemic has lasted more than one and half years and continues to threaten the world. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the vaccine is considered an effective way to contain the COVID-19 pandemic. For emergency use, including four types of COVID-19 vaccines: mRNA, inactivated virus, viral vector-based and recombinant protein vaccine. BNT162b2, as the first mRNA vaccine approved by WHO, has shown high effectiveness and safety in clinical trials [1,2]. ChAdOx1(AZD1222) is a type of viral vector-based vaccine which looks to insert the SARS-CoV-2 spike protein gene into the chimpanzee adenovirus vector ChAdOx1 for replication, providing 70.4% vaccine effectiveness [4]. The recombinant protein vaccine NVX-CoV2373 (Novavax) has not been included in the emergency use list, it has been shown to be 89.7% effective in the clinical trial, and the efficacy against variant B.1.1.7 was approximately 86.3% [5]

Objectives

Results

Discussion

Conclusion