Expression of Bordetella pertussis Antigens Fused to Different Vectors and Their Effectiveness as Vaccines.

Han Xu,Kangfeng Wang,Zhaolu Liu,Hengliang Wang,Xin Li,Jun Wu,Jing Huang,Chao Pan,Kaihu Yao,Erling Feng,Li Zhu

doi:10.3390/vaccines9060542

Abstract

Pertussis is an acute respiratory tract infection caused by Bordetella pertussis. Even though its current vaccine coverage is relatively broad, they still have some shortcomings such as short protection time and might be incapable of blocking the spread of the disease. In this study, we developed new pertussis vaccine candidates by separately fusing three pertussis antigens (B. pertussis fimbriae 2 “Fim2”, pertussis toxin S1 subunit “PtxS1”, and filamentous hemagglutinin “FHA1877–2250”) to each of two immune-boosting carrier proteins (B subunits of AB5 toxin family: cholera toxin B subunit “CTB” and shiga toxin B subunit “StxB”). We then immunized mice with these fusion antigens and found that they significantly increased the serum antibody titers and elicited high bactericidal activity against B. pertussis. After CTB-or StxB-fused antigen-immunized mice were challenged with a non-lethal dose of B. pertussis, the bacterial loads in different tissues of these mice were significantly reduced, and their lung damage was nearly invisible. Furthermore, we also demonstrated that these candidate vaccines could provide strong prophylactic effects against a lethal challenge with B. pertussis. Overall, our candidate vaccines conferred better immune protection to mice compared with pertussis antigen alone. This B5 subunit-based vaccine strategy provides a promising option for vaccine design.

Highlights

The results show the detection of high expression bands at approximately 34, 27, and 36 kDa in the antigenonly lanes, which correspond to the molecular weights of fimbriae 2 (Fim2)-SUMO (Fim2-S), pertussis toxin S1 subunit (PtxS1), and FHA1877–2250, respectively
Increases in the molecular weights of these fusion protein bands were observed in the lanes containing CTB-Fim2, StxB-Fim2-SUMO (StxB-Fim2-S), CTB-PtxS1-SUMO (CTB-PtxS1-S), StxB-PtxS1-SUMO (StxB-PtxS1-S), CTB-FHA1877–2250, and StxB-FHA1877–2250, which corresponded with their expected molecular weights (Figure 1A)
Vaccines are a primary method for preventing bacterial infections

Summary

Introduction

Pertussis is a serious respiratory disease that is mainly characterized by persistent and paroxysmal coughing, with a characteristic inspiratory “whooping” sound. Because a typical infection generally lasts for three months, pertussis is known as the “hundredday cough” [1]. This disease is caused by B. pertussis, an organism mainly spread via aerosols and able to colonize the respiratory tract, where it damages epithelial cells and impairs normal respiratory function. Epidemiological surveys have shown that pertussis outbreaks generally occur every 3–5 years [2]. The number of reported cases has risen to 20,000 to 40,000 confirmed and presumed cases a year [3]

Methods

Results

Conclusion