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Title: Helminth infection impairs the immunogenicity of a Plasmodium falciparum DNA vaccine, but not irradiated sporozoites, in mice

Author
item NOLAND, GREGORY - Johns Hopkins University
item CHOWDHURY, DABABANI - Johns Hopkins University
item Urban, Joseph
item ZAVALA, FIDEL - Johns Hopkins University
item KUMAR, NIRBHAY - Johns Hopkins University

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/25/2010
Publication Date: 4/9/2010
Citation: Noland, G.S., Chowdhury, D.R., Urban Jr, J.F., Zavala, F., Kumar, N. 2010. Helminth infection impairs the immunogenicity of a Plasmodium falciparum DNA vaccine, but not irradiated sporozoites, in mice. Vaccine. 28(17):2917-2923.

Interpretive Summary: Concurrent helminth (worm) infection can alter optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied in the context of different vaccine preparations for the same infectious agent. Demands for new and effective vaccines to control chronic and emerging diseases, and the need for rapid deployment of vaccines for bio security concerns requires a systematic evaluation of confounding factors that limit vaccine efficacy. One common confounder is the presence of worm parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were human infections are prevalent and in livestock worldwide that are routinely exposed to parasitic infection. The current report studied the vaccination of mice experimentally infected with Heligmosomoides polygyrus to model this condition. Worm infection prior to intramuscular vaccination with a Pfs25 containing DNA plasmid with sequences for a 25-kDa cysteine-rich protein that is expressed on the surface of zygotes and ookinetes of Plasmodium falciparum malaria as well as intravenous vaccination with whole irradiated sporozoites of a mouse malaria species inhibited the expected antibody class that typically provides protective immunity in the former but not later scenario. This atypical skewing of the immune response by the worm parasite suggested that eliminating the worm infection would enhance optimal vaccination especially with modern vaccines that use DNA technology. This information is important to scientists working to provide effective vaccine strategies for a variety of infectious agents.

Technical 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 boostings, 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.