Caister Academic Press

Progress in Passive Immunotherapy

Ana P. Goncalvez, Robert H. Purcell, and Ching-Juh Lai
from: Frontiers in Dengue Virus Research (Edited by: Kathryn A. Hanley and Scott C. Weaver). Caister Academic Press, U.K. (2010)

Abstract

Dengue is currently endemic in more than one hundred countries around the world. It causes approximately 50-100 million infections annually, including 250,000-500,000 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). According to the World Health Organization (WHO), two fifths of the world population is at risk of dengue virus (DENV) infection. It has been suggested that globalization and climate change have had a significant impact on the emergence of DENV in new areas. No vaccine or therapy against DENV is currently approved for use in humans, and alternative strategies to control DENV infection are urgently needed, particularly because the design of such strategies may also inform efforts in vaccine design. This chapter outlines the prophylaxis/therapeutic potential of monoclonal antibodies (MAbs) against DENV and highlights the challenges to implementation of this strategy, including antibody-dependent enhancement (ADE), genetic variability of DENV strains, potential for selection of MAb escape variants, and financial cost. Moreover, we describe recent immunologic and structural studies that have provided a new understanding of antibody-mediated neutralization mechanisms and protection against DENV and other flavivirus infections. These insights are having an important impact on the development of vaccines and antibody-based therapies.

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