Vaccination Strategies against Highly Pathogenic Arenaviruses

Highly Pathogenic Arenaviruses The family Arenaviridae contains four important species that cause severe hemorrhagic zoonoses in humans. Together, they have an important impact on public health in endemic regions. Lassa virus (LASV) is endemic to Africa. The other three species (Machupo, Junin, and Guanarito viruses [MACV, JUNV, and GTOV]) are from South America. The prototypic arenavirus is lymphocytic choriomeningitis virus (LCMV), which can also cause disease in humans, especially in immunocompromised patients.

Arenaviruses carry two RNA genome segments (small, S, and large, L), which encode two genes each. The S-segment encodes the glycoprotein precursor (GPC) and, in ambisense, the nucleoprotein (NP). Similarly, the L-segment encodes the matrix protein Z and, in negative sense, the multifunctional protein L. Natural reservoirs include different species of rodents, depending on the arenavirus. The exact mode of transmission to humans is unknown but probably occurs through direct contact with the infected host or food contaminated with excrement. Direct human-to-human transmission is possible and regularly occurs in clinical settings in endemic areas.

Little is known about the pathogenesis of the diseases caused by arenaviruses. A putative explanation for the severe symptoms is an immunopathology caused by an imbalanced host–pathogen interaction with a perpetuated excessive reaction of host immune cells combined with delayed viral clearance. Early immune evasion may participate in the disease through delayed virus clearance. Treatment options for the patients are limited. In addition to intensive care, the broad-band antiviral drug ribavirin has proven to be effective if administered early in the course of the disease. The caveat is the need for early diagnosis, and this is a genuine problem, since infections with arenaviruses are initially often mistaken for malaria, typhoid fever, or other common tropical diseases due to the nonspecific nature of the symptoms. The only currently available vaccine is Candid #1. This attenuated JUNV strain was generated through multiple passaging and provided good protection in clinical trials against argentine hemorrhagic fever (AHF) with an excellent safety profile. The historical development and biological properties of this vaccine were recently reviewed in a concise overview.

Although there has been much effort to develop vaccines against LASV, none have been effective enough to warrant clinical trials. This short review summarizes the work that has been done toward the development of vaccines against hemorrhagic fever caused by arenaviruses and discusses the obstacles toward a licensed vaccine.

Vaccination Strategies against Highly Pathogenic Arenaviruses: The Next Steps toward Clinical Trials. (2013) PLoS Pathog 9(4): e1003212. doi:10.1371/journal.ppat.1003212

 

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