title: Vaccination with intestinal tract antigens does not induce protective immunity in a permissive model of filariasis.
abstract: Antigens obtained from the intestinal tract of filarial nematodes have been proposed as potential safe and effective vaccine candidates. Because they may be 'hidden' from the immune response during natural infection, yet accessible by antibodies induced by vaccination, intestinal antigens may have a low potential for eliciting allergic responses when vaccinating previously infected individuals. Despite prior promising data, vaccination with intestinal antigens has yet to be tested in a permissive model of filariasis. In this study we investigated the efficacy of vaccination with filarial intestinal antigens in the permissive Litomosoides sigmodontis BALB/c model of filariasis, and we evaluated the extent to which these antigens are recognized by the immune system during and after infection. Infected BALB/c mice developed lower IgG antibody responses to soluble intestinal antigens (GutAg) than to soluble antigens of whole worms (LsAg). Similarly, GutAg induced less proliferation and less production of IL-4 and IFNγ from splenocytes of infected mice than LsAg. In contrast to these differences, active infection resulted in equivalent levels of circulating GutAg-specific IgE and LsAg-specific IgE levels. Consistent with this, basophil activation, as assessed by flow cytometric staining of intracellular basophil IL-4 expression, was equivalent in response to GutAg and LsAg. Vaccination with GutAg adsorbed to CpG/alum induced GutAg specific IgG1 and IgG2A production, with GutAg specific IgG titers greater than 5-fold higher than those measured in previously infected animals. Despite this response to GutAg vaccination, vaccinated mice harbored similar parasite burdens 8 weeks post infection when compared to non-vaccinated controls. These studies demonstrate that soluble antigens obtained from the intestinal tracts of L. sigmodontis have some qualities of 'hidden' antigens, but they still sensitize mice to allergic reactions and fail to protect against future infection when given as a vaccine adsorbed to alum/CPG.
authors.affiliation: Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD 20852, USA.
authors.forename: C Paul
authors.initials: CP
authors.lastname: Morris
authors.forename: Marina N
authors.initials: MN
authors.lastname: Torrero
authors.forename: David
authors.initials: D
authors.lastname: Larson
authors.forename: Holly
authors.initials: H
authors.lastname: Evans
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Shi
authors.forename: Rachel T
authors.initials: RT
authors.lastname: Cox
authors.forename: Edward
authors.initials: E
authors.lastname: Mitre
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D000947:Antigens, Helminth / Q000008:administration & dosage* / Q000276:immunology; D001491:Basophils / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005368:Filariasis / Q000276:immunology / Q000517:prevention & control*; D005370:Filarioidea / Q000276:immunology*; D005849:Gerbillinae; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007422:Intestines / Q000276:immunology; D007814:Larva / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014611:Vaccination / Q000592:standards*
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D007074:Immunoglobulin G; D007073:Immunoglobulin E
keywords: Antigen; Filaria; Helminth; Hidden; Intestine; Litomosoides sigmodontis; Vaccine