Abstract

The development of COVID-19 vaccines is critical in controlling global health issues under the COVID-19 pandemic. The subunit vaccines are the safest and most widely used vaccine platform and highly effective against a multitude of infectious diseases. An adjuvant is essential for subunit vaccines to enhance the magnitude and durability of immune responses. In this study, we determined whether a combination of toll-like receptor (TLR)1/2 and TLR3 agonists (L-pampo) can be a potent adjuvant for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine. We measured a neutralizing antibody (nAb) and an angiotensin-converting enzyme 2 (ACE2) receptor-blocking antibody against SARS-CoV-2 receptor-binding domain (RBD). We also detected interferon-gamma (IFN-γ) production by using ELISPOT and ELISA assays. By employing a ferret model, we detected nAbs and IFN-γ producing cells and measured viral load in nasal wash after the challenge of SARS-CoV-2. We found that SARS-CoV-2 antigens with L-pampo stimulated robust humoral and cellular immune responses. The efficacy of L-pampo was higher than the other adjuvants. Furthermore, in the ferret model, SARS-CoV-2 antigens with L-pampo elicited nAb response and antigen-specific cellular immune response against SARS-CoV-2, resulting in substantially decreased viral load in their nasal wash. Our study suggests that SARS-CoV-2 antigens formulated with TLR agonists, L-pampo, can be a potent subunit vaccine to promote sufficient protective immunity against SARS-CoV-2.

Highlights

  • The new emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic since early 2020

  • By using the ferret model which is a suitable animal model for SARSCoV-2 infection, we found that receptor-binding domain (RBD) and S1 with L-pampo elicited strong neutralizing antibody (nAb) response against SARS-CoV-2 and increased both RBD- and S1-specific cellular immune responses

  • We evaluated RBD- and S1-specific Abs that can inhibit the engagement of SARS-CoV-2 antigens to angiotensin-converting enzyme 2 (ACE2), which serves as an entry receptor [15,16,17]

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Summary

Introduction

The new emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic since early 2020. The World Health Organization (WHO) reported that 141 million cases of COVID-19 were confirmed and over 3 million died worldwide as of April 2021 [1]. To control the spread of COVID-19 globally, the development of safe and effective vaccines is urgently needed. Burgeoning global efforts have developed several vaccines based on mRNA technology or a virus-vector platform. These vaccines are not able to meet global vaccination requirements, and their long-term efficacy and safety concerns are under investigation [2]. Growing evidences indicate that recovered patients cannot be completely excluded from the population requiring vaccination due to reinfection or SARS-CoV-2 variants [3,4]. Alternative vaccine approaches against SARS-CoV-2 are constantly required

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