Immunoproteomic Analysis of Human Serological Antibody Responses to Vaccination with Whole-Cell Pertussis Vaccine (WCV)

Abstract

BACKGROUND: Pertussis (whooping cough) caused by Bordetella pertussis (B.p), continues to be a serious public health threat. Vaccination is the most economical and effective strategy for preventing and controlling pertussis. However, few systematic investigations of actual human immune responses to pertussis vaccines have been performed. Therefore, we utilized a combination of two-dimensional electrophoresis (2-DE), immunoblotting, and mass spectrometry to reveal the entire antigenic proteome of whole-cell pertussis vaccine (WCV) targeted by the human immune system as a first step toward evaluating the repertoire of human humoral immune responses against WCV. METHODOLOGY/PRINCIPAL FINDINGS: Immunoproteomic profiling of total membrane enriched proteins and extracellular proteins of Chinese WCV strain 58003 identified a total of 30 immunoreactive proteins. Seven are known pertussis antigens including Pertactin, Serum resistance protein, chaperonin GroEL and two OMP porins. Sixteen have been documented to be immunogenic in other pathogens but not in B.p, and the immunogenicity of the last seven proteins was found for the first time. Furthermore, by comparison of the human and murine immunoproteomes of B.p, with the exception of four human immunoreactive proteins that were also reactive with mouse immune sera, a unique group of antigens including more than 20 novel immunoreactive proteins that uniquely reacted with human immune serum was confirmed. CONCLUSIONS/SIGNIFICANCE: This study is the first time that the repertoire of human serum antibody responses against WCV was comprehensively investigated, and a small number of previously unidentified antigens of WCV were also found by means of the classic immunoproteomic strategy. Further research on these newly identified predominant antigens of B.p exclusively against humans will not only remarkably accelerate the development of diagnostic biomarkers and subunit vaccines but also provide detailed insight into human immunity mechanisms against WCV. In particular, this work highlights the heterogeneity of the B.p immunoreactivity patterns of the mouse model and the human host