dominant cross-reactive b cell response during secondary acute dengue virus infection in humans主要可交叉反应的b细胞反应在继发性急性登革热病毒感染人类.pdfVIP

Dominant Cross-Reactive B Cell Response during Secondary Acute Dengue Virus Infection in Humans 1 2 1 2 1 Simona Zompi *, Magelda Montoya , Marie O. Pohl , Angel Balmaseda , Eva Harris * 1 Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California, United States of America, 2 Laboratorio Nacional de ´ ´ Virologıa, Centro Nacional de Diagnostico y Referencia, Ministerio de Salud, Managua, Nicaragua Abstract The four serotypes of dengue virus (DENV) cause dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Severe disease has been associated with heterotypic secondary DENV infection, mediated by cross- reactive antibodies (Abs) and/or cross-reactive T cells. The role of cross-reactive immunity in mediating enhanced disease versus cross-protection against secondary heterotypic DENV infection is not well defined. A better understanding of the cross-reactive immune response in natural infections is critical for development of safe and effective tetravalent vaccines. We studied the B cell phenotype of circulating B cells in the blood of pediatric patients suspected of dengue during the 2010–2011 dengue season in Managua, Nicaragua (n = 216), which was dominated by the DENV-3 serotype. We found a markedly larger percentage of plasmablast/plasma cells (PB/PCs) circulating in DENV-positive patients as compared to patients with Other Febrile Illnesses (OFIs). The percentage of DENV-specific PB/PCs against DENV-3 represented 10% of the circulating antibody-producing cells (ASCs) in secondary DENV-3 infections. Importantly, the cross-reactive DENV-specific B cell response was higher against a het