Abstract
Live-attenuated vaccines (LAV) represent one of the most important medical innovations in human history. In the past three centuries, LAV have saved hundreds of millions of lives, and will continue to do so for many decades to come. Interestingly, the most successful LAVs, such as the smallpox vaccine, the measles vaccine, and the yellow fever vaccine, have been isolated and/or developed in a purely empirical manner without any understanding of the immunological mechanisms they trigger. Today, the mechanisms governing potent LAV immunogenicity and long-term induced protective immunity continue to be elusive, and therefore hamper the rational design of innovative vaccine strategies. A serious roadblock to understanding LAV-induced immunity has been the lack of suitable and cost-effective animal models that can accurately mimic human immune responses. In the last two decades, human-immune system mice (HIS mice), i.e., mice engrafted with components of the human immune system, have been instrumental in investigating the life-cycle and immune responses to multiple human-tropic pathogens. However, their use in LAV research has remained limited. Here, we discuss the strong potential of LAVs as tools to enhance our understanding of human immunity and review the past, current and future contributions of HIS mice to this endeavor.
Highlights
Live-attenuated vaccines (LAVs) have saved millions of lives and continue to prove themselves as one of the most important inventions in modern medical history
We recently reported that NODRAG1−/− IL2Rγnull (NRG) mice engrafted with human hematopoietic stem cells (HSC) (NRG-HIS) are susceptible to yellow fever virus (YFV)-17D [249]
Using NRG-HIS mice and mice depleted for Stat1 signaling in the hematopoietic compartment, we identified species-specific interactions between YFV-17D and this compartment that potentially regulate the outcome of infection
Summary
Live-attenuated vaccines (LAVs) have saved millions of lives and continue to prove themselves as one of the most important inventions in modern medical history. A single dose of yellow fever vaccine provides protection against the disease for at least ten years [4]. While some concerns remain about the ability of LAVs to revert toward a wild-type genotype in humans, the adverse effects and risks associated with these vaccines remain very low and are clearly outweighed by the health benefits they provide at a global scale. Over recent years, alarming episodes of pathogen (re-) emergence for which there are no licensed vaccines, such as Ebola, Lassa, or Zika virus, have been witnessed [5,6,7]. The emergence potential of currently neglected pathogens such as Powassan virus and Eastern equine Encephalitis
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