DNA vaccine candidate encoding SARS-CoV-2 spike proteins elicited potent humoral and Th1 cell-mediated immune responses in mice.

Eakachai Prompetchara,Tanapat Palaga,Kittipan Tharakhet,Supaporn Watcharaplueksadee,Suwitra Sathean-Anan-Kun,Supaporn Phumiamorn,Wassana Wijagkanalan,Supranee Buranapraditkun,Kiat Ruxrungtham,Patrawadee Pitakpolrat,Kanitha Patarakul,Teerasit Techawiwattanaboon,Papatsara Kaewpang,Chutitorn Ketloy,Paulo Lee Ho

doi:10.1371/journal.pone.0248007

Abstract

More than 65 million people have been confirmed infection with SARS-CoV-2 and more than 1 million have died from COVID-19 and this pandemic remains critical worldwide. Effective vaccines are one of the most important strategies to limit the pandemic. Here, we report a construction strategy of DNA vaccine candidates expressing full length wild type SARS-CoV-2 spike (S) protein, S1 or S2 region and their immunogenicity in mice. All DNA vaccine constructs of pCMVkan-S, -S1 and -S2 induced high levels of specific binding IgG that showed a balance of IgG1/IgG2a response. However, only the sera from mice vaccinated with pCMKkan-S or -S1 DNA vaccines could inhibit viral RBD and ACE2 interaction. The highest neutralizing antibody (NAb) titer was found in pCMVkan-S group, followed by -S1, while -S2 showed the lowest PRNT50 titers. The geometric mean titers (GMTs) were 2,551, 1,005 and 291 for pCMVkan-S, -S1 and -S2, respectively. pCMVkan-S construct vaccine also induced the highest magnitude and breadth of T cells response. Analysis of IFN-γ positive cells after stimulation with SARS-CoV-2 spike peptide pools were 2,991, 1,376 and 1,885 SFC/106 splenocytes for pCMVkan-S, -S1 and -S2, respectively. Our findings highlighted that full-length S antigen is more potent than the truncated spike (S1 or S2) in inducing of neutralizing antibody and robust T cell responses.

Highlights

In December 2019, the outbreak of pneumonia caused by an unknown pathogen was documented in the city of Wuhan in China
The S protein is a trimeric transmembrane protein required for binding to its host receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) located in the S1 region while the S2 region is responsible for virus-membrane fusion [10, 11]
S1/S2 protein-specific antibody responses were strongly elicited by SARS-CoV-2 DNA vaccine candidates

Summary

Introduction

In December 2019, the outbreak of pneumonia caused by an unknown pathogen was documented in the city of Wuhan in China. The vaccine for the current outbreak must be produced at a high speed and be scalable [5]. The lessons learnt and information from previous related coronaviruses outbreak, such as SARS in 2003 and MERS in 2012, revealed that the immune responses against viral spike (S) protein played an important role in viral infection inhibition [8,9,10]. There are at least 10 vaccine candidates testing in phase III trials [12, 19]. Any of these candidates may receive an emergency use approval for people at high risk by the end of 2020 or early 2021. Whether an effective vaccine against SARS-CoV-2 will be available sooner or later, scientific research to help further improvement of the generation vaccine is warranted

Methods

Results

Conclusion