Journal Article

An adjuvant formulation containing Toll-like Receptor 7 agonist stimulates protection against morbidity and mortality due to Anaplasma marginale in a highly endemic region of west Africa

Palmer, Guy H., Zumor-Baligi, Songliedong, Ashiagbor, Charles N. K., Fox, Christopher B., Futse, James E., Noh, Susan M.

2024

Overview

Efficient cattle production and provision of animal-sourced foods in much of Africa is constrained by vector-borne bacterial and protozoal diseases. Effective vaccines are not currently available for most of these infections resulting in a continuous disease burden that limits genetic improvement. We tested whether stimulation of innate immunity using the Toll-like Receptor (TLR) 7 agonist imiquimod, formulated with saponin and water-in-oil emulsion, would protect against morbidity and mortality due to Anaplasma marginale , a tick-borne pathogen of cattle highly endemic in west Africa. In Trial 1, haplotype matched Friesian x Sanga (F1) A . marginale negative calves were allocated to either the experimental group (n = 10) and injected with the synthetic TLR 7 agonist/saponin formulation or to an untreated control group (n = 10). TLR7 agonist/saponin injected calves responded with significantly elevated rectal temperature, enlarged regional lymph nodes, and elevated levels of IL-6 post-injection as compared to control group calves. All calves were then allowed to graze in pasture for natural exposure to tick transmission. All calves in both groups acquired A . marginale , consistent with the high transmission rate in the endemic region. The need for antibiotic treatment, using pre-existing criteria, was significantly lower in the experimental group (odds ratio for not requiring treatment was 9.3, p = 0.03) as compared to the control group. Despite treatment, 6/10 calves in the control group died, reflecting treatment failures that are typical of anaplasmosis in the acute phase, while mortality in the experimental group was 1/10 (odds ratio for survival was 13.5, p = 0.03). The trial was then repeated using 45 Friesian x Sanga calves per group. In Trial 2, the odds ratios for preventing the need for treatment and for mortality in the TLR7 agonist/saponin experimental group versus the control group were 5.6 (p = 0.0002) and 7.0 (p = 0.004), respectively, reproducing the findings of the initial trial. Together these findings demonstrate that innate immune stimulation using a TLR7 agonist formulated with saponin and water-in-oil emulsion provides significant protection against disease caused by tick borne A . marginale in highly susceptible cross-bred cattle, critically important for their potential to increase productivity for smallholder farmers in Africa.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adjuvants, Immunologic - pharmacology / Adjuvants, Pharmaceutic / Africa, Western / Agonists / Anaplasma marginale / Anaplasma marginale - immunology / Anaplasmosis / Anaplasmosis - prevention & control / Animals / Antibiotics / Biology and Life Sciences / Blood / Calves / Cattle / Cattle Diseases - immunology / Cattle Diseases - microbiology / Cattle Diseases - mortality / Cattle Diseases - prevention & control / Cattle production / Cytokines / Disease transmission / Diseases / Dosage and administration / Emulsions / Endemic Diseases - prevention & control / Endemic Diseases - veterinary / Food availability / Food sources / Haplotypes / Health services / Imiquimod / Immune system / Immunity (Disease) / Infection / Infections / Infectious diseases / Innate immunity / Lymph nodes / Lymphatic system / Medicine and Health Sciences / Morbidity / Mortality / Oxytetracycline / Pasture / Patient outcomes / Phlebotomy / Physical Sciences / Proteins / Saponins / Saponins - pharmacology / Small farms / Stimulation / Temperature / Testing / TLR7 protein / Toll-Like Receptor 7 - agonists / Toll-like receptors / Vaccines / Vector-borne diseases