Rational Design of a Chimeric Derivative of PcrV as a Subunit Vaccine Against Pseudomonas aeruginosa

In this study, the full-length PcrV was divided into four domains with the guidance of its structure, and the Nter domain (Met1-Lys127) and H12 domain (Leu251-Ile294) were found to be immunodominant. Subsequently, Nter and H12 were combined with a flexible linker to generate an artificial PcrV derivative (PcrVNH). PcrVNH was successfully produced in E. coli and behaved as a homogenous monomer. Moreover, immunization with PcrVNH elicited a multifactorial immune response and conferred broad protection in an acute PA pneumonia model and was equally effective to full-length PcrV. In addition, passive immunization with anti-PcrVNH antibodies alone also showed significant protection, at least based on inhibition of the T3SS and mediation of opsonophagocytic killing activities. These results provide an additional example for the rational design of antigens and suggest that PcrVNH is a promising vaccine candidate for the control of PA infection. Introduction Pseudomonas aeruginosa (PA) is a major cause of nosocomial infections in patients with compromised immunity (1). In patients with impaired respiratory functions, PA-induced pneumonia contributes to a larger proportion of mortality, such as from cystic fibrosis (2), long-term mechanical ventilation (3), and COPD (4). With increased drug resistance, the effectiveness of antibiotic therapies is limited. As a result, it remains difficult to combat PA infection despite supportive treatments. Vaccines could be an alternative st...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research