Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1.

Khalid A Alluhaybi,Najwa D Aljehani,Adel M Abuzenadah,Rowa Y Alhabbab,Wanyue Zhang,Anwar M Hashem,Mohamed A Alfaleh,Mohammad Basabrain,Sawsan S Alamri,Abdullah Algaissi,Mazen Hassanain,Xuguang Li,Levi Tamming,Wesam H Abdulaal,Rahaf H Alharbi,Rehaf Alharbi

doi:10.3390/vaccines9080852

Khalid A Alluhaybi, Najwa D Aljehani + Show 14 more

Open Access

https://doi.org/10.3390/vaccines9080852

Copy DOI

Abstract

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

Highlights

The emergence and rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, represent a serious public health and economic burden to humanity [1,2,3,4]
Numerous studies on SARS-CoV-2 and other pathogenic human CoVs such as MERS-CoV and SARSCoV have dementated that most of the neutralizing antibodies (nAbs) that are generated due to either natural infection or full-length S based vaccines target the subunit 1 (S1) subunit, making S1 an attractive and probably safer immunogen for vaccine development [35,36,37,38,39]. This is due to the fact that S1 contains the receptor-binding domain (RBD) and the N-terminal motif (NTD) which are critical for mediating binding to the host receptor
We successfully developed and evaluated the immunogenicity of a new DNA vaccine candidate against SARS-CoV-2, encoding the S1 subunit of the S protein

Summary

Introduction

The emergence and rapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, represent a serious public health and economic burden to humanity [1,2,3,4]. The emergence and rapid spread of the severe acute respiratory syndrome-coronavirus-. Hundreds of SARS-CoV-2 vaccines have been or are being developed using traditional and innovative technology platforms [9]. Several of these vaccines were approved for emergency use by multiple regulatory agencies across the globe. Other developers have adopted innovative technologies and/or novel approaches for antigen design, gene expression and vector optimization, including adenovirus-based vaccines [11,12,13,14] as well as mRNA vaccines [15]. Additional platforms being used include novel viral vectors, recombinant subunit proteins, nanoparticles and plasmid DNA [16,17,18]

Methods

Results

Conclusion