Infection with parasitic nematodes confounds vaccination efficacy

Abstract

T helper (Th) cells produce signature cytokine patterns, induced largely by intracellular versus extracellular pathogens that provide the cellular and molecular basis for counter regulatory expression of protective immunity during concurrent infections. The production of IL-12 and IFN-γ, for example, resulting from exposure to many bacterial, viral, and protozoan pathogens is responsible for Th1-derived protective responses that also can inhibit development of Th2-cells expressing IL-4-dependent immunity to extracellular helminth parasites and vice versa. In a similar manner, concurrent helminth infection alters optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied especially in the context of a challenge infection following vaccination. 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 albeit overlooked confounder is the presence of gastrointestinal nematode parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were helminth infections are prevalent, but the interplay between parasites and emerging diseases that can be transmitted worldwide make this a global issue. In addition, it is not clear if the epidemic in allergic disease in industrialized countries substitutes for geohelminth infection to interfere with effective vaccination regimens. This presentation will focus on recent vaccination NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript studies in mice experimentally infected with Heligmosomoides polygyrus to model the condition of gastrointestinal parasite infestation in mammalian populations targeted for vaccination. In addition, a large animal vaccination and challenge model against Mycoplasma hyopneumonia in swine exposed to Ascaris suum will provide a specific example of the need for further work in this area, and for controlled field studies to assess the impact of other similar scenarios.

Coinfection withHeligmosomoides polygyrusFails To Establish CD8+T-Cell Immunity againstToxoplasma gondii

“…Based on our data, this factor should be seriously considered while developing vaccination strategies against these agents. In fact, a recent review has suggested that vaccine efficacy using both crude and defined antigens can be severely impaired in animals coinfected with helminths and protozoan and bacterial pathogens (40). These observations along with effects of coinfection on inflammation indicate a need for more definitive studies to explore parasite-related products as immune modulators and the mechanisms related to control of infection and tissue reactivity.…”

Helminth Infections and Host Immune Regulation

“…Moreover, vaccine responses were significantly augmented in Ascaris-infected children given anthelmintic treatment prior to immunization, compared to the responses of placebo-treated controls (53), while a similar comparison of infected and treated recipients of Mycobacterium bovis BCG showed that helminth infections depressed antimycobacterial T cell responses, with concomitant increases in levels of TGF-␤ release (72). Investigations using mouse models have reiterated these effects (287). For example, S. mansoni infection interferes with the protective effect of BCG vaccination (71), and Heligmosomoides polygyrus infection reduces the efficacy of vaccination against Plasmodium chabaudi (268).…”

Helminth parasites in pigs: New challenges in pig production and current research highlights

“…The consequences of the delicate balance between the different arms of the immune system may be of immense practical importance. First, helminth infections may downregulate the Th1 responses against bacteria and viruses thereby reducing the efficacy of vaccinations (Urban et al, 2007), as recently described for Mycoplasma hyopneumoniae vaccination in pigs infected with A. suum (Steenhard et al, 2009). Secondly, the lack of helminth induced immunomodulation in the human populations of the industrialised countries has been hypothesised to contribute to the steep increase in autoimmune diseases, such as inflammatory bowel disease, type 1 diabetes, and multiple sclerosis (reviewed by McKay, 2006;Elliott et al, 2007;Zaccone et al, 2007;Fleming, 2011).…”