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Generating prophylactic immunity against arboviruses in vertebrates and invertebrates

Nature Reviews Immunology (2024)Cite this article

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Abstract

The World Health Organization recently declared a global initiative to control arboviral diseases. These are mainly caused by pathogenic flaviviruses (such as dengue, yellow fever and Zika viruses) and alphaviruses (such as chikungunya and Venezuelan equine encephalitis viruses). Vaccines represent key interventions for these viruses, with licensed human and/or veterinary vaccines being available for several members of both genera. However, a hurdle for the licensing of new vaccines is the epidemic nature of many arboviruses, which presents logistical challenges for phase III efficacy trials. Furthermore, our ability to predict or measure the post-vaccination immune responses that are sufficient for subclinical outcomes post-infection is limited. Given that arboviruses are also subject to control by the immune system of their insect vectors, several approaches are now emerging that aim to augment antiviral immunity in mosquitoes, including Wolbachia infection, transgenic mosquitoes, insect-specific viruses and paratransgenesis. In this Review, we discuss recent advances, current challenges and future prospects in exploiting both vertebrate and invertebrate immune systems for the control of flaviviral and alphaviral diseases.

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Fig. 1: Flavivirus and alphavirus infections: viraemia, disease course, diagnosis and treatment.
Fig. 2: Whole virion vaccines and antibody-induced protection.
Fig. 3: Augmenting mosquito immunity to inhibit flavivirus and alphavirus transmission.

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Acknowledgements

A.S. is funded by an investigator grant from the National Health and Medical Research Council (NHMRC) of Australia (APP1173880) ‘Chikungunya and Zika viruses; understanding disease and developing interventions’. G.J.D. is a chief investigator on an NHMRC grant (APP2012404) ‘Removing mosquito populations by releasing incompatible males’. L.E.H. is a principal investigator on an NHMRC grant (APP2012500) ‘Mosquito-specific viruses: novel agents to control transmission of arboviral pathogens’. The authors thank the Brazil Family Foundation for their generous philanthropic donations to support PC3-based virus research at QIMR Berghofer Medical Research Institute. The funders had no role in the preparation of the manuscript or in the decision to publish. The authors thank N. Beebe for his helpful input.

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  1. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    Daniel J. Rawle, Leon E. Hugo, Abigail L. Cox, Gregor J. Devine & Andreas Suhrbier

  2. GVN Centre of Excellence, Australian Infectious Disease Research Centre, Brisbane, Queensland, Australia

    Gregor J. Devine & Andreas Suhrbier

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All authors researched data for the article. D.J.R., L.E.H., G.J.D. and A.S. contributed substantially to the discussion of the content. A.S., G.J.D. and L.E.H. wrote the article. D.J.R. and A.S. reviewed and/or edited the manuscript before submission. A.L.C. designed the original concepts for the figures.

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Correspondence to Andreas Suhrbier.

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A.S. is a chief investigator on a Medical Research Future Fund grant (Australia) and will receive research grant funding from that grant for preclinical evaluation of mRNA vaccines; the principal unvestigator is Southern RNA. A.S. and D.J.R. are chief investigators on an NHMRC development grant application and may receive research grant funding from that grant for preclinical evaluation of chimeric insect-specific virus vaccines; the principal investigator and patent holders are from the University of Queensland. The other authors declare no competing interests.

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Rawle, D.J., Hugo, L.E., Cox, A.L. et al. Generating prophylactic immunity against arboviruses in vertebrates and invertebrates. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-01016-6

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