Location: Animal Parasitic Diseases Laboratory
Project Number: 8042-32000-116-007-R
Project Type: Reimbursable Cooperative Agreement
Start Date: Sep 5, 2019
End Date: Jun 30, 2023
To compare the intestinal transcriptomes of Ancylostoma and Haemonchus (both blood-feeding nematode parasites) isolated from immunocompetent and immunocompromised hosts (hamsters for Ancylostoma, sheep for Haemonchus), use comparative transcriptomics and immunoinformatics to identify prioritized vaccine targets, and test these as prophylactic vaccines first in hamsters (validate) and then in sheep.
Aim 1 Approach: (ARS and Collaborator) Perform RNA-seq with Haemonchus intestines and use comparative genomics/transcriptomics/immunoinformatics with hookworm data to prioritize vaccine candidates. A. Perform RNA-seq of H. contortus intestines dissected from immunocompetent/immunosuppressed sheep. B. Identify and select high-priority vaccine antigen candidates based on intestinal transcriptome commonalities (intestinal-specificity; induced by host immune system) between Haemonchus and Ancylostoma and by performing immunoinformatics on common candidates between the two parasites. Aim 2 Approach: (Collaborator) Test/validate prioritized vaccine antigen candidates from Aim 1 in vivo with hamster-hookworm. A. Optimize rAceyCP1 vaccine efficacy in hamsters by testing expression systems, adjuvants, and multiunit vaccine potential with rAceyAPR1. B. Vaccinate/test with high-priority candidates from Aim 1B singly against Ancylomosta infections in hamsters. C. Vaccinate/test with combinations of successful antigens from Aims 2A and B. Aim 3 Approach: (ARS) Study the vaccine efficacies of validated antigen candidates in vivo with sheep-Haemonchus. A. Vaccinate/test with Haemonchus CP1-like proteins (rHcCP1) and rHcAPR1 against Haemonchus infections in sheep. B. Vaccinate/test with validated vaccine antigen candidates from Aims 2A and 2B singly and/or in combination against Haemonchus infections in sheep (n=3 sheep/group). C. Vaccinate/test with validated vaccine antigen candidates from Aim 3B against Haemonchus in larger scale sheep trial (n=6 sheep/group).