Strategies of rational and structure-driven vaccine design for Arenaviruses

The COVID-19 outbreak has highlighted the importance of pandemic preparedness for the prevention of future health crises. One virus family with high pandemic potential are Arenaviruses, which have been detected almost worldwide, particularly in Africa and the Americas. These viruses are highly understudied and many questions regarding their structure, replication and tropism remain unanswered, making the design of an efficacious and molecularly-defined vaccine challenging. We propose that structure-driven computational vaccine design will contribute to overcome these challenges. Computational methods for stabilization of viral glycoproteins or epitope focusing have made progress during the last decades and particularly during the COVID-19 pandemic, and have proven useful for rational vaccine design and the establishment of novel diagnostic tools. In this review, we summarize gaps in our understanding of Arenavirus molecular biology, highlight challenges in vaccine design and discuss how structure-driven and computationally informed strategies will aid in overcoming these obstacles. [Display omitted] •Rational and structure-based vaccine is crucial to the success of Arenavirus vaccines.•Accurate GPC structure prediction is key to successful structure-based vaccine design.•In depth analysis of Arenavirus GPC structures needs to be undertaken.•ADE needs to be investigated in the context of Arenaviruses.•Many details regarding Arenavirus receptors remain elusive.