Abstract
Viral hemorrhagic fever viruses come from a wide range of virus families and are a significant cause of morbidity and mortality worldwide each year. Animal models of infection with a number of these viruses have contributed to our knowledge of their pathogenesis and have been crucial for the development of therapeutics and vaccines that have been approved for human use. Most of these models use artificially high doses of virus, ensuring lethality in pre-clinical drug development studies. However, this can have a significant effect on the immune response generated. Here I discuss how the dose of antigen or pathogen is a critical determinant of immune responses and suggest that the current study of viruses in animal models should take this into account when developing and studying animal models of disease. This can have implications for determination of immune correlates of protection against disease as well as informing relevant vaccination and therapeutic strategies.
Highlights
Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Abstract: Viral hemorrhagic fever viruses come from a wide range of virus families and are a significant cause of morbidity and mortality worldwide each year
These types of studies resulted in the identification of monoclonal antibodies as a suitable therapeutic option for treatment of Ebola virus (EBOV) infection. While this value has been recognized, determining what types of immune responses are protective during hemorrhagic fever virus infections requires models of infection that are representative of the majority of human infections or those representing the most severe forms of infection
A hamster-adapted Marburg virus (MARV) was reported, providing another suitable model to examine disease [75]. Ferrets represent another viable option for EBOV, Sudan ebolavirus (SUDV), and Bundibugyo virus infections, and they recapitulate hallmarks of humans disease when infected with wild-type viruses, something that gives them an advantage over other small animal models [62,76]
Summary
Hemorrhagic fever viruses, defined here as viruses that can cause fever and hemorrhagic disease, include a number of viruses that are a significant cause of morbidity and mortality worldwide. An important aspect of developing vaccines is determining immune correlates of protection against infection and disease development, and animal modelling in addition to human data can be informative in this regard These types of studies resulted in the identification of monoclonal antibodies as a suitable therapeutic option for treatment of EBOV infection. While this value has been recognized, determining what types of immune responses are protective during hemorrhagic fever virus infections requires models of infection that are representative of the majority of human infections or those representing the most severe forms of infection. I examine some of the current literature around animal models of hemorrhagic fevers, and make the case that for studying pathogen-specific immune responses and their relevance in protective immunity, a shift in how experiments are conducted may be needed
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