Intranasal vaccination with a recombinant protein CTA1-DD-RBF protects mice against hRSV infection

Hai Li,Hu Ren,Yan Zhang,Lei Cao,Wenbo Xu

doi:10.1038/s41598-021-97535-6

Abstract

Human respiratory syncytial virus (hRSV) infection is a major pediatric health concern worldwide. Despite more than half a century of efforts, there is still no commercially available vaccine. In this study, we constructed and purified the recombinant protein CTA1-DD-RBF composed of a CTA1-DD mucosal adjuvant and prefusion F protein (RBF) using Escherichia coli BL21 cells. We studied the immunogenicity of CTA1-DD-RBF in mice. Intranasal immunization with CTA1-DD-RBF stimulated hRSV F-specific IgG1, IgG2a, sIgA, and neutralizing antibodies as well as T cell immunity without inducing lung immunopathology upon hRSV challenge. Moreover, the protective immunity of CTA1-DD-RBF was superior to that of the RBF protein, as confirmed by the assessment of serum-neutralizing activity and viral clearance after challenge. Compared to formalin-inactivated hRSV (FI-RSV), intranasal immunization with CTA1-DD-RBF induced a Th1 immune response. In summary, intranasal immunization with CTA1-DD-RBF is safe and effective in mice. Therefore, CTA1-DD-RBF represents a potential mucosal vaccine candidate for the prevention of human infection with hRSV.

Highlights

Human respiratory syncytial virus is an orthopneumovirus belonging to the Pneumoviridae family[1]
CTA1-DD-RBF was purified by HisTrap FF columns, and the tags were removed by overnight digestion with thrombin at 26 °C
SDS-PAGE analysis indicated that the purified CTA1-DD-RBF was ≥ 90% pure, and a 90 kDa band was identified (Fig. 1B)

Summary

Introduction

Human respiratory syncytial virus (hRSV) is an orthopneumovirus belonging to the Pneumoviridae family[1]. The highly conserved F protein can induce antibodies against infections caused by hRSV of both subgroups A and B9 and is a key target in the development of subunit vaccines, particle-like vaccines and viral vector-based vaccines[10,11,12]. The hRSV-neutralizing antibodies AM22, D25 and 5C4 (specific to prefusion F protein) have been found to be substantially more potent than palivizumab (which binds both the pre-F and post-F proteins)[18,19]. Previous research suggests that the F-ctxA2B fusion protein consists of residues 412–524 of the hRSV F protein and that the ctxA2B subunit of CT can provide partial protection[44], no research has been performed on the CTA1-DD mucosal adjuvant used in hRSV vaccines until now

Methods

Results

Conclusion