Search

The complete lack of yellow fever virus (YFV) in Asia, and the lack of urban YFV transmission in South America, despite the abundance of the peridomestic mosquito vector Aedes (Stegomyia.) aegypti is an enigma. An immunologically naïve population of over 2 billion resides in Asia, with most regions infested with the urban YF vector. One hypothesis for the lack of Asian YF, and absence of urban YF in the Americas for over 80 years, is that prior immunity to related flaviviruses like dengue (DENV) or Zika virus (ZIKV) modulates YFV infection and transmission dynamics. Here we utilized an interferon α/β receptor knock-out mouse model to determine the role of pre-existing dengue-2 (DENV-2) and Zika virus (ZIKV) immunity in YF virus infection, and to determine mechanisms of cross-protection. We utilized African and Brazilian YF strains and found that DENV-2 and ZIKV immunity significantly suppresses YFV viremia in mice, but may or may not protect relative to disease outcomes. Cross-protection appears to be mediated mainly by humoral immune responses. These studies underscore the importance of re-assessing the risks associated with YF outbreak while accounting for prior immunity from flaviviruses that are endemic.

Lassa virus (LASV) is a zoonotic pathogen endemic throughout western Africa and is responsible for a human disease known as Lassa fever (LF). Historically, LASV has been emphasized as one of the greatest public health threats in West Africa, with up to 300,000 cases and 5000 associated deaths per year. This, and the fact that the disease has been reported in travelers, has driven a rapid production of various vaccine candidates. Several of these vaccines are currently in clinical development, despite limitations in understanding the immune response to infection. Alarmingly, the host immune response has been implicated in the induction of sensorineural hearing loss in LF survivors, legitimately raising safety questions about any future vaccines as well as efficacy in preventing potential hearing loss. The objective of this article is to revisit the importance and prevalence of LF in West Africa, with focus on Nigeria, and discuss current therapeutic approaches and ongoing vaccine development. In addition, we aim to emphasize the need for more scientific studies relating to LF-associated hearing loss, and to promote critical discussion about potential risks and benefits of vaccinating the population in endemic regions of West Africa.

Eastern (EEEV), Venezuelan (VEEV), and western equine encephalitis viruses (WEEV) are members of the genus Alphavirus, family Togaviridae. Typically spread by mosquitoes, EEEV, VEEV, and WEEV induce febrile illness that may develop into more severe encephalitic disease, resulting in myriad severe neurologic sequelae for which there are no vaccines or therapeutics. Here, we summarize the clinical neurologic findings and sequelae induced by these three encephalitic viruses and describe the various animal models available to study them. We emphasize the crucial need for the development of advanced animal modeling combined with the use of telemetry, behavioral testing, and neuroimaging to facilitate a detailed mechanistic understanding of these encephalitic signs and sequelae. Through the use of these systems, much-needed therapeutics and vaccines can be developed.