Successful immunization against a parasitic nematode by vaccination with recombinant proteins

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.

Novel expression of Haemonchus contortus vaccine candidate aminopeptidase H11 using the free-living nematode Caenorhabditis elegans

“…Recent studies aimed at developing a recombinant vaccine against the related sheep GI nematode T. circumcincta , demonstrated significant reductions in FEC using a cocktail of eight recombinant proteins [53]. It is likely that multicomponent vaccines are required for adequate protection against complex metazoan parasites.…”

Progress in the development of subunit vaccines for gastrointestinal nematodes of ruminants

“…All proteins were expressed in E. coli, with the exception of Tci‐CF‐1 and Tci‐ES20, which were expressed in P. pastoris . This eight‐protein cocktail was administered to sheep three times with Quil A adjuvant and the animals then subjected to a third‐stage larval “trickle” challenge, which was designed to mimic field conditions . In two trials in six‐ to seven‐month‐old lambs, significant levels of protection were obtained in vaccinates compared to adjuvant‐only recipients.…”

“…This is further supported by the higher proliferation of immune cells in the mesenteric lymph nodes of animals immunized with the C. oncophora vaccine in comparison with adjuvant control animals . Quil A is generally considered a type‐1 adjuvant and is also the adjuvant used in the successful subunit vaccination studies against T. circumcincta in sheep . Together with the inability of aluminium hydroxide to provoke a protective response, this challenges the paradigm that a protective immune response against most helminth infections is driven by Th2 cells .…”

Ectoparasites of medical and veterinary importance: drug resistance and the need for alternative control methods

“…(2006) observed that ingestion of a protease inhibitor cocktail caused mortality in D. gallinae ;[136] and antibodies directed against the digestive enzymes cathepsin D and cathepsin L caused increased mortality when delivered to poultry mites in an in vitro feeding system [137]. A successful vaccine has not yet been produced against either of these mite species; however, it is possible that the various antigens assessed so far could be used in a combination vaccine, which has proved to be a successful approach for protection against the gastrointestinal nematode Teladorsagia circumcincta [138]…”