Characterization of Immune Reactivity Profiles Using Microarray Technology May Expedite Identification of Candidate Antigens for Next Generation Malaria Vaccines

Abstract

Vaccines have proven to be one of the most successful and efficient means of controlling infectious diseases of public health importance, including smallpox, polio, pertussis, and measles (1). The annual global burden of 300–500 million new malaria cases and 1–3 million malaria-related deaths demonstrates the potential public health and socioeconomic benefit that would accrue with the deployment of a highly effective malaria vaccine, particularly for the most affected and impoverished populations (2). However, despite several decades of research and substantial evidence for its feasibility, such a vaccine remains elusive (3). Among the many challenges facing vaccine developers is how to mine the human immune response to natural infection to identify protective antigens and associated host responses. While there is no evidence that sterile immunity is ever naturally induced by the parasite, both symptoms and parasite density gradually decline with repeated exposure, resulting in a state of clinical and partial parasitological immunity (4). Thus young children living in endemic areas are at the greatest risk for high-density infections and for clinical disease, including severe complications, whereas older children and adults are rarely symptomatic, although they may harbor and transmit the parasite. A variety of data implicate antibody responses to multiple blood stage antigens as the primary effector mechanism underlying naturally acquired immunity; the antigenic targets, however, have not been clearly identified. Our limited understanding of the array of protective (and nonprotective) immune responses is reflected by the small number of antigens under development as candidate vaccines or shown to be protective in experimental challenge models (5)(6). Indeed, current generation subunit vaccines are based on a few “traditional” antigens (7) despite evidence that antimalarial immunity is likely multifactorial, targeting many antigens and involving antibody responses, T cell responses, cytokines, natural killer cells, and many additional effector mechanisms (8) …