Novel approaches for the rapid development of rationally designed arbovirus vaccines

Joyce W M van Bree; Imke Visser; Jo M Duyvestyn; Muriel Aguilar-Bretones; Eleanor M Marshall; Martijn J van Hemert; Gorben P Pijlman; Gijsbert P van Nierop; Marjolein Kikkert; Barry H G Rockx; Pascal Miesen; Jelke J Fros

doi:10.1016/j.onehlt.2023.100565

Novel approaches for the rapid development of rationally designed arbovirus vaccines

One Health. 2023 May 13:16:100565. doi: 10.1016/j.onehlt.2023.100565. eCollection 2023 Jun.

Affiliations

¹ Laboratory of Virology, Wageningen University & Research, Wageningen, the Netherlands.
² Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
³ Department of Medical Microbiology, Leiden University Medical Centre, Leiden, the Netherlands.
⁴ Department of Medical Microbiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, P.O. Box 9101, 6500, HB, Nijmegen, the Netherlands.

Abstract

Vector-borne diseases, including those transmitted by mosquitoes, account for more than 17% of infectious diseases worldwide. This number is expected to rise with an increased spread of vector mosquitoes and viruses due to climate change and man-made alterations to ecosystems. Among the most common, medically relevant mosquito-borne infections are those caused by arthropod-borne viruses (arboviruses), especially members of the genera Flavivirus and Alphavirus. Arbovirus infections can cause severe disease in humans, livestock and wildlife. Severe consequences from infections include congenital malformations as well as arthritogenic, haemorrhagic or neuroinvasive disease. Inactivated or live-attenuated vaccines (LAVs) are available for a small number of arboviruses; however there are no licensed vaccines for the majority of these infections. Here we discuss recent developments in pan-arbovirus LAV approaches, from site-directed attenuation strategies targeting conserved determinants of virulence to universal strategies that utilize genome-wide re-coding of viral genomes. In addition to these approaches, we discuss novel strategies targeting mosquito saliva proteins that play an important role in virus transmission and pathogenesis in vertebrate hosts. For rapid pre-clinical evaluations of novel arbovirus vaccine candidates, representative in vitro and in vivo experimental systems are required to assess the desired specific immune responses. Here we discuss promising models to study attenuation of neuroinvasion, neurovirulence and virus transmission, as well as antibody induction and potential for cross-reactivity. Investigating broadly applicable vaccination strategies to target the direct interface of the vertebrate host, the mosquito vector and the viral pathogen is a prime example of a One Health strategy to tackle human and animal diseases.

Keywords: Alphavirus; Arbovirus; Flavivirus; Live-attenuated vaccines; Mosquito-borne virus; chimeric viruses; mosquito saliva; pre-clinical model systems; recoded viruses.