Deep Mutational Scanning of Dengue Viruses for Vaccine Development
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Description
Emerging viral infections are a global threat to public health. Dengue is a mosquito-borne viral disease of common occurrence in most tropical and many subtropical areas. The only licensed vaccine available shows suboptimal protective efficacy especially for Dengue serotype 2. Consequently, vector control measures are the only widely used means of disease prevention and development of more potent and cross-reactive dengue vaccine would represent a major advance in disease control. Research to identify vaccines has been hampered by limitations of conventional approaches that cannot comprehensively search for useful viral mutations. The current project aims to implement an approach that combines a novel massively parallel experimental technique and a virus construction technique developed in our lab to comprehensively test dengue virus mutants for their resistance to a host immune response. This exercise will identify novel mutations that affect dengue resistance to a key antiviral pathway. It will produce a collection of dengue mutants with varying degree of host resistance, enabling us to test different levels of viral attenuation which is critical for finding optimal immune responses for developing an effective vaccine. Characterizations of these viruses by a battery of immunological and virological assays will give us an idea of the relationship between viral attenuation and the ensuing immune response, key information for fine tuning the efficacy of a dengue vaccine. Future application of this exercise to investigate multiple interactions between virus and host immunity could accelerate our path to identify the elusive correlates of protection for dengue in humans.
Objectives
The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
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