The Impact of BKI-1294 Therapy in Mice Infected With the Apicomplexan Parasite Neospora caninum and Re-infected During Pregnancy

Frontiers in Veterinary Science
Pablo WinzerAndrew Hemphill

Abstract

Exposure of Neospora caninum tachyzoites to BKI-1294 in vitro results in the formation of long-lived multinucleated complexes (MNCs). However, in vivo treatment of BALB/c mice with BKI-1294 shortly after N. caninum infection during pregnancy was safe and profoundly reduced pup mortality and vertical transmission. We hypothesized that the formation of MNCs could trigger immune responses that contribute to BKI efficacy in vivo. In this study, mice were first vaccinated with a sublethal dose of N. caninum tachyzoites and were treated with BKI-1294. We then investigated the effects of these treatments after mating and re-infection during pregnancy. Effects on fertility, pup survival, vertical transmission, and parasite load in dams were evaluated. Cytokines in sera or splenocyte culture supernatants were assessed by either ELISA or the Luminex™ 200 system, and humoral immune responses against tachyzoite and MNC antigens were compared by ELISA, Western blotting and immunoproteomics. Our results showed that BKI-1294 treatment of live-vaccinated mice reduced the cerebral parasite load in the dams, but resulted in higher neonatal pup mortality and vertical transmission. In live-vaccinated mice, cytokine levels, most notably IFN-y, IL-1...Continue Reading

References

Feb 1, 1996·Parasitology·A HemphillH Kaufmann
Jun 14, 2002·International Journal for Parasitology·Anna LundénDavid Buxton
May 12, 2005·International Journal for Parasitology·Catherine MillerJohn T Ellis
Aug 17, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Sherry A Dunbar
Apr 4, 2006·The Journal of Eukaryotic Microbiology·S RamamoorthyN Sriranganathan
Jun 17, 2009·Cell Host & Microbe·Oliver BillkerL David Sibley
May 4, 2010·Nature Structural & Molecular Biology·Kayode K OjoWesley C Van Voorhis
Dec 14, 2011·International Journal for Parasitology·Daniel C LimJeroen P J Saeij
Mar 1, 2012·Journal of Medicinal Chemistry·Eric T LarsonEthan A Merritt
May 17, 2012·Microbes and Infection·Diego Miranda-SaavedraChristian Doerig
Mar 8, 2014·Experimental Parasitology·Thierry Monney, Andrew Hemphill
Feb 11, 2015·Vaccine·Michael P ReichelJohn T Ellis
Jun 18, 2016·Parasite Immunology·P HorcajoL M Ortega-Mora
Jan 10, 2017·Experimental Parasitology·Wesley C Van VoorhisKayode K Ojo
Aug 24, 2017·Journal of Veterinary Pharmacology and Therapeutics·M L StockW H Hsu
Sep 14, 2017·International Journal for Parasitology·Adriana Aguado-MartínezAndrew Hemphill
Mar 5, 2018·International Journal for Parasitology. Drugs and Drug Resistance·Roberto Sánchez-SánchezLuis Miguel Ortega-Mora
Apr 1, 2020·International Journal for Parasitology·Ryan ChoiWesley C Van Voorhis
Apr 30, 2020·Chembiochem : a European Journal of Chemical Biology·Oksana DesiatkinaJulien Furrer

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
PCR
Assay
Enzyme Linked Immunosorbent Assay
acetylation
ELISA

Software Mentioned

Easyprot
Ubuntu

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.