Immune response of lambs to vaccination with Ostertagia circumcincta surface antigens eliciting bile antibody responses.
ABSTRACT Immune responses to surface antigens of infective larvae of Ostertagia circumcincta recognized by bile antibodies of sheep immune to challenge were studied in 5-month-old Finn-Dorset male lambs. The sheep were vaccinated subcutaneously with 2 doses of 25 micrograms/kg body weight of surface proteins immunoprecipitated by bile antibodies derived from protected lambs. These antigens were purified from immune complexes by affinity chromatography and then injected with beryllium hydroxide as an adjuvant. The immunized lambs were challenged with 5 x 10(4) L3 and the worm burdens evaluated on day 21 post challenge. These were significantly (P < 0.01) lower in the vaccinated group than in the challenged controls (72% protection). The mucosal and bile IgM, recognizing the L3 surface, showed significantly higher levels in the vaccinated lambs compared to the challenge controls. Mucosal and bile IgA antibody levels against the same antigens were low and no significant differences were observed between vaccinated and control lambs.
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ABSTRACT: Infection of small ruminants with Teladorsagia circumcincta has, until now, been controlled using a combination of pasture management and frequent anthelmintic treatments. Resistance to the commonly used anthelmintics has driven research into the development of a subunit vaccine, encouraged by the demonstration of development of protective immunity in sheep following exposure to this parasite. Local immune effectors in the abomasum, in particular IgA, are thought to play important roles in naturally- and experimentally-acquired immunity. L3s represent the first contact of this pathogen with the host immune system and, herein, the presence of L3 antigen-specific IgA was demonstrated in abomasal mucus from immune sheep. This antibody source was used to immunoaffinity purify and identify IgA-reactive molecules present in L3s. We identified 155 different proteins in this way, including a number of activation-associated secretory proteins (ASP), venom allergen-like (VAL)-type proteins, detoxifying enzymes, galectins and a suite of other potential vaccine candidate molecules. Levels of immunoaffinity-enriched L3 antigen-specific IgA in gastric lymph from previously-infected sheep were statistically significantly higher (P = 0.004) than those measured in helminth-free sheep and a statistically significant negative correlation (P = 0.005, rs = -0.565) was identified between immunoaffinity-enriched L3 antigen-specific IgA levels in efferent gastric lymph and total T. circumcincta burden measured at necropsy. In addition, a statistically significant positive correlation (P = 0.007, rs=0.534) was measured between immunoaffinity-enriched L3 antigen-specific IgA levels in efferent gastric lymph and the percentage of inhibited L4s enumerated at necropsy. These results indicate that the purified antigens contain components that could be strongly considered as vaccine candidates.International Journal for Parasitology 07/2014; · 3.40 Impact Factor
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ABSTRACT: Global food security will require the production of more food using resources including land more efficiently, and with less waste. This goal must be achieved within the context of climate change and while ensuring minimal adverse environmental impact from both crop and livestock production. Disease, especially infectious disease, is a main constraint of biologically efficient livestock production and both endemic and exotic disease results in mortality and morbidity and hence less food than should ideally be available in current farming systems. A significant proportion of diseases affect the safety of food supplies, in addition to or instead of, their effect on volume and quality of food products. Parasitological diseases including those caused by nematodes, trematodes, protozoa and ectoparasites, have widely differing effects on meat, milk and fibre production and many new technologies have been developed in order to prevent or treat them. Approaches to developing better control of parasites have included livestock breeding strategies, improved nutrition and management, and the development of new drugs, diagnostic tests and vaccines. Some of the most important examples include both the development of new anthelmintic products, and better means of using existing drugs in order to maximise their effectiveness in the face of rapidly increasing parasite resistance; diagnostic tests which are able to detect low levels of nucleic acids or proteins from infectious agents rapidly; and vaccines derived from either native or recombinant proteins and designed to stimulate the most appropriate protective response from livestock species. Some of the parasitic diseases affect restricted regions around the world, however most affect very large global populations. The development of technologies of suitable and affordable livestock products for use in developing countries where most pressure on increased production for food will occur, provides a particular challenge. Most if not all new technologies form part of integrated management schemes on farms and these vary hugely in differing systems and geographical regions of the world. If the benefit of improved technologies for optimal health, welfare and biological efficiency of livestock is to be realised, then the veterinary, farming, commercial animal health and public service communities need to learn lessons from past successes and failures in the delivery of newly developed technologies to the farmer. The combination of technology and rural development in the veterinary parasitological field has played a key role in current food production and is well placed to continue this trend to help in ensuring future food requirements for the world.Veterinary Parasitology 04/2013; · 2.55 Impact Factor
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ABSTRACT: Infection of humans and livestock with parasitic nematodes can have devastating effects on health and production, affecting food security in both developed and developing regions. Despite decades of research, the development of recombinant sub-unit vaccines against these pathogens has been largely unsuccessful. We have developed a strategy to identify protective antigens from Teladorsagia circumcincta, the major pathogen causing parasitic gastroenteritis in small ruminants in temperate regions, by studying IgA responses directed at proteins specific to post-infective larvae. Antigens were also selected on the basis of their potential immunomodulatory role at the host/parasite interface. Recombinant versions of eight molecules identified by immunoproteomics, homology with vaccine candidates in other nematodes and/or with potential immunoregulatory activities, were therefore administered to sheep in a single vaccine formulation. The vaccine was administered three times with Quil A adjuvant and the animals subsequently subjected to a repeated challenge infection designed to mimic field conditions. Levels of protection in the vaccinates were compared to those obtained in sheep administered with Quil A alone. The trial was performed on two occasions. In both trials, vaccinates had significantly lower mean fecal worm egg counts (FWECs) over the sampling period, with a mean reduction in egg output of 70% (Trial 1) and 58% (Trial 2). During the period of peak worm egg shedding, vaccinates shed 92% and 73% fewer eggs than did controls in Trials 1 and 2, respectively. At post mortem, vaccinates had 75% (Trial 1) and 56% (Trial 2) lower adult nematode burdens than the controls. These levels of protection are the highest observed in any system using a nematode recombinant sub-unit vaccine in the definitive ruminant host and indicate that control of parasitic helminths via vaccination with recombinant subunit vaccine cocktails is indeed an alternative option in the face of multi-drug resistance.Vaccine 05/2013; · 3.49 Impact Factor