title: Helminth infection impairs the immunogenicity of a Plasmodium falciparum DNA vaccine, but not irradiated sporozoites, in mice.
abstract: Development of an effective vaccine against malaria remains a priority. However, a significant number of individuals living in tropical areas are also likely to be co-infected with helminths, which are known to adversely affect immune responses to a number of different existing vaccines. Here we compare the response to two prototype malaria vaccines: a transmission blocking DNA vaccine based on Pfs25, and a pre-erythrocytic malaria vaccine based on irradiated sporozoites in mice infected with the intestinal nematode Heligmosomoides polygyrus. Following primary immunization with Pfs25 DNA vaccine, levels of total IgG, as well as IgG1, IgG2a, IgG2b (all P=0.0002), and IgG3 (P=0.03) Pfs25 antibodies were significantly lower in H. polygyrus-infected mice versus worm-free controls. Similar results were observed even after two additional boosts, while clearance of worms with anthelmintic treatment 3 weeks prior to primary immunization significantly reversed the inhibitory effect of helminth infection. In contrast, helminth infection had no inhibitory effect on immunization with irradiated sporozoites. Mean anti-CSP antibody responses were similar between H. polygyrus-infected and worm-free control mice following immunization with a single dose (65,000 sporozoites) of live radiation attenuated (irradiated) Plasmodium yoelii sporozoites (17X, non-lethal strain), and protection upon sporozoite challenge was equivalent between groups. These results indicate that helminth infection may adversely affect certain anti-malarial vaccine strategies, and highlight the importance of these interactions for malaria vaccine development.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Noland
authors.forename: Debabani Roy
authors.initials: DR
authors.lastname: Chowdhury
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Urban
authors.forename: Fidel
authors.initials: F
authors.lastname: Zavala
authors.forename: Nirbhay
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D005260:Female; D006374:Helminthiasis, Animal / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009351:Nematospiroides dubius / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology* / Q000528:radiation effects; D034101:Sporozoites / Q000276:immunology / Q000528:radiation effects; D014613:Vaccines, Attenuated / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA