ABSTRACT
In previous studies using a murine model of filarial infection, granuloma formation was found to be a most important host-protective mechanism. We have also shown that in vitro cytoadherence is a surrogate for the formation of antifilarial granulomas in vivo and that it requires "alternatively activated" host cells and a source of antifilarial antibody. We show here that antibodies against L3 excretory/secretory (E/S) products can facilitate in vitro cytoadherence. We generated a set of hybridomas reactive with filarial E/S products and screened them for their ability to mediate in vitro cytoadherence. One clone (no. 1E9) was positive in this assay. We then screened a novel expression library of filarial antigens displayed on the surface of T7 bacteriophage for reactivity with 1E9. Phage expressing two filarial antigens (TCTP and BmALT-2) reacted with 1E9. Immunization of mice showed that the cohort immunized with BmALT-2 cleared a challenge infection with infective Brugia pahangi L3 in an accelerated manner, whereas cohorts immunized with TCTP cleared larvae with the same kinetics as in unimmunized mice. These data confirm that BmALT-2 is the antigenic target of granuloma-mediated killing of B. pahangi L3. Our findings also confirm previous studies that BmALT-2 is a potential vaccine candidate for filarial infection. Our data reinforce the work of others and also provide a possible mechanism by which immune responses to BmALT-2 may provide host protection.
Subject(s)
Antigens, Helminth/immunology , Brugia pahangi/immunology , Filariasis/prevention & control , Granuloma/parasitology , Vaccines/immunology , Animals , Antibodies, Helminth/immunology , Brugia pahangi/anatomy & histology , Epitopes/immunology , Filariasis/immunology , Hybridomas , Immunoglobulin M/immunology , Integumentary System , Larva/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Recombinant Proteins/immunology , Specific Pathogen-Free Organisms , Tumor Protein, Translationally-Controlled 1ABSTRACT
PURPOSE: To describe strategies for a comprehensive literature search. ORGANIZING CONSTRUCT: MEDLINE searches result in limited numbers of studies that are often biased toward statistically significant findings. Diversified search strategies are needed. METHODS: Empirical evidence about the recall and precision of diverse search strategies is presented. Challenges and strengths of each search strategy are identified. FINDINGS: Search strategies vary in recall and precision. Often sensitivity and specificity are inversely related. Valuable search strategies include examination of multiple diverse computerized databases, ancestry searches, citation index searches, examination of research registries, journal hand searching, contact with the "invisible college," examination of abstracts, Internet searches, and contact with sources of synthesized information. CONCLUSIONS: Extending searches beyond MEDLINE enables researchers to conduct more systematic comprehensive searches.
