Repeated, drug-truncated infections with Ostertagia ostertagi elicit strong humoral and cell-mediated immune responses

Authors: Tuo, Wenbin; Zarlenga, Dante; BAKSHI, MARIAM - Non ARS Employee; Vinyard, Bryan

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/24/2021
Publication Date: 6/26/2021
Citation: Tuo, W., Zarlenga, D.S., Bakshi, M., Vinyard, B.T. 2021. Repeated, drug-truncated infections with Ostertagia ostertagi elicit strong humoral and cell-mediated immune responses. Veterinary Parasitology. 296:109510. https://doi.org/10.1016/j.vetpar.2021.109510.
DOI: https://doi.org/10.1016/j.vetpar.2021.109510

Interpretive Summary: Bovine ostertagiasis causes significant production losses to the cattle industry. Protective immunity induced by natural infection is slow to develop; yet parasite anthelmintic resistance continues to rapidly develop. Thus, there is a need to identify alternatives for control of gastrointestinal nematode parasites. The present study investigated if repeated, drug-truncated infections (rDTI) could induce robust immune responses and protection against challenge infection. The results show that rDTI procedure reduced (P<0.01) infection and improved (P=0.0564) weight gain in treated animals. Parasite-specific antibody and T cells responses were highly boosted by challenge infection. These data indicate that protective immunity against ostertagiasis can be elicited by exposing the host to killed in-tissue parasites at overlapping stages. This rDTI immunization model can be used to study host-parasite interactions and to discover candidate vaccine targets against gastrointestinal nematodes.

Technical Abstract: Bovine ostertagiasis causes significant production losses to the cattle industry. Protective immunity induced by natural infection is slow to develop and anthelmintic resistance is rapidly developing. There is a need to advance alternatives for control of gastrointestinal nematode parasites. The present study investigated the effects of repeated, drug-truncated infections (rDTI) on development of protective immunity and attenuation of a challenge infection by O. ostertagi. Helminth-free calves were randomly assigned to either a DTI or a control group (n=5). The DTI group received daily oral infections of 5,000 Ostertagia L3 for 5 consecutive days, then were drug-treated on 14 and 15 days post infection (dpi), to attenuate O. ostertagi at the late L4 larvae, young adult stage. DTI was repeated 3 weeks after the drug treatment. A total of 5 DTI treatments were administered; control animals received drug treatments at the same time. The results show that eggs per gram of feces (EPG) in the DTI group were significantly reduced (P<0.05) from 21 to 37 dpi, with an overall reduction in cumulative EPG of approximately 50%. The control group exhibited reduced (P=0.0564) average weight gains when compared to those of the rDTI group during weeks 4-5 post infection, a period coinciding with peak EPG output of control animals. Antigen-specific IgG and IgA responses were detected after the 2nd DTI, and stronger Ab recall responses were elicited by challenge infection. High levels of antigen-specific PBMC/T cell proliferation to whole worm and ES antigens were detected in rDTI-treated animals. These data indicate that partial protective immunity against ostertagiasis, involving cell-mediated and humoral responses, can be attained by rDTI which allowed for maximal antigen exposure from staggered parasitic developmental stages. The data suggest that rDTI can be used as a model to study host-parasite interactions and identify parasite antigens responsible for eliciting host protective immune responses.