Title

Alt 2: A central protective antigen in filarial infection

Date of Completion

January 2007

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

Lymphatic Filariasis affects more than 120 million people in 83 countries around the world. Individuals living in endemic areas show a broad range of immunoreactivities and disease manifestations. It is not clear why certain individuals appear to be completely resistant to the disease while other otherwise immunosufficient individuals are susceptible. The first step in understanding the susceptibility and or resistance of these individuals to infection is to identify antigens against which protective immunity can be generated. ^ In this thesis we have used multiple approaches to identify the source and nature of protective antigens that would protect against an infection with B. pahangi parasites. Here, using an intraperitoneal mouse model of infection we have demonstrated that both the L3 released excretory/secretory (E/S) products as well as the cuticle obtained from the L3-L4 molt can prime mice to produce accelerated clearance of B. pahangi L3 (a measure of protection). This shows that protective antigens are present in both E/S products as well as in the L3 cuticle. Further we have determined that these antigens are proteins in nature. ^ This work also sought to identify a specific antigen that would protect mice against a challenge infection. Here we have demonstrated that a larval protein Brugia malayi abundant larval transcript 2 (Bm Alt-2), identified using phage display library screening approaches, can be used to generate protective immunity. ^ The ultimate goal of identifying candidate protective antigens is to induce long lasting protective immunity. In order to do this we must first understand the nature of immunological memory formed following natural infection. Here we have immunized mice of two different strains BALB/c and C57B1/6 over long periods of time and challenged them at a common time point to determine the longevity of immunological memory. Here we demonstrate that BALB/c but not C57BU6 mice develop long lived immunological memory. ^