Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA

Yuan Liu,Xiaoli Feng,Jianbao Han,Nan Zhang,Hua Zhu,Xiling Guo,Chuan Qin,Lianpan Dai,Ran Gao,Minghua Li,Jiangning Liu,Bin Wang,Linlin Bao,Qingcui Zou,Yi Zhang

doi:10.1186/s43556-021-00054-z

Abstract

In the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

Highlights

As of Sep 2021, according to the WHO, more than 221 million infections and nearly 4.6 million deaths were confirmed with coronavirus disease 2019 (COVID-19) worldwide [1]
S‐trimer adjuvanted with PIKA induces fast, robust, long‐lasting and broad neutralizing antibody response against SARS‐CoV‐2 in rabbits To express a trimeric form of prefusion stabilized fulllength S protein, we fused the trimerization domain of T4 to the amino acid residues 15–1208 of SARS-CoV-2 spike protein (Fig. 1a)
S‐trimer adjuvanted with PIKA induces a balanced Th1/Th2 immune response in mice We further evaluated the IgG subclass response of mice immunized with S-trimer adjuvanted with or without PIKA to determine Th1/Th2 polarization

Summary

Introduction

As of Sep 2021, according to the WHO, more than 221 million infections and nearly 4.6 million deaths were confirmed with coronavirus disease 2019 (COVID-19) worldwide [1]. PIKA adjuvant, as a synthetic chemical analogue of a double-stranded RNA (dsRNA), acts as other dsRNA in activating an immune response through recognition by TLR3 [14,15,16]. Another important dsRNA-signaling pathway is initiated by the RNA helicase RIG-I. Recent phase I and phase II clinical studies of inactivated purified rabies virus adjuvanted by PIKA (PIKA Rabies vaccine) showed that the vaccine was safe and more immunogenic or noninferior immunogenicity than the commercially available vaccine in healthy adults [18, 19] These encouraging study data strongly support PIKA as an adjuvant of COVID-19 vaccine

Methods

Results

Conclusion