Current Efforts in the Development of Vaccines for the Prevention of Zika and Chikungunya Virus Infections

Abstract

Arboviruses represent major challenges to public health, particularly in tropical, and subtropical regions, and a substantial risk to other parts of the world as respective vectors extend their habitats. In recent years, two viruses transmitted by Aedes mosquitoes, Chikungunya and Zika virus, have gathered increased interest. After decades of regionally constrained outbreaks, both viruses have recently caused explosive outbreaks on an unprecedented scale, causing immense suffering and massive economic burdens in affected regions. Chikungunya virus causes an acute febrile illness that often transitions into a chronic manifestation characterized by debilitating arthralgia and/or arthritis in a substantial subset of infected individuals. Zika infection frequently presents as a mild influenza-like illness, often subclinical, but can cause severe complications such as congenital malformations in pregnancy and neurological disorders, including Guillain-Barré syndrome. With no specific treatments or vaccines available, vector control remains the most effective measure to manage spread of these diseases. Given that both viruses cause antibody responses that confer long-term, possibly lifelong protection and that such responses are cross-protective against the various circulating genetic lineages, the development of Zika and Chikungunya vaccines represents a promising route for disease control. In this review we provide a brief overview on Zika and Chikungunya viruses, the etiology and epidemiology of the illnesses they cause and the host immune response against them, before summarizing past and current efforts to develop vaccines to alleviate the burden caused by these emerging diseases. The development of the urgently needed vaccines is hampered by several factors including the unpredictable epidemiology, feasibility of rapid clinical trial implementation during outbreaks and regulatory pathways. We will give an overview of the current developments.

Dengue and Zika Viruses: Epidemiological History, Potential Therapies, and Promising Vaccines

“…Recent data of the clinical trials demonstrated that the vaccine induced a long-term immune response, reducing the risk of symptomatic disease regardless of the person serostatus [ 143 , 144 ]. For ZIKV, no vaccines are available, but several candidates are under development, including in clinical trials [ 133 , 145 , 146 ]. One of those candidates, VRC 705 (National Institute of Allergy and Infectious Diseases/Vaccine Research Center), elicits good immunogenic response, now in phase II clinical trial (NCT03110770) [ 145 , 146 , 147 ].…”

Prophylactic strategies to control chikungunya virus infection

“…Climate change, international travel and other unforeseen factors might promote vector emergence and spread in such a way that even developed countries are at risk of becoming endemic for CHIKV, presenting another potential market for a vaccine. The fact that FDA and the EMA have granted Fast Track- and Priority Medicine status to multiple vaccine candidates should inspire further confidence in the for-profit entities regarding the potential market [ 145 ].…”

“…Recognising the current epidemiological problems and the need for a CHIKV vaccine, the WHO has published a R&D blueprint in which the principles in the design, conduct and analysis of Phase2b/Phase 3 clinical trials to evaluate Chikungunya vaccines are outlined [ 149 ].The WHO’s suggested trial design is a Phase 3 prospective, double-blind, placebo-controlled, efficacy trial [ 149 ]. While this study design is considered the “gold standard” in epidemiologic studies, it seems that the “traditional approval” pathway does not work to receive a BLA for a CHIKV vaccine for various reasons [ 145 ].…”

Injection site vaccinology of a recombinant vaccinia-based vector reveals diverse innate immune signatures

“…A single construct recombinant SCV vaccine encoding the structural gene cassettes of both chikungunya virus (CHIKV) and Zika virus (ZIKV) (SCV-ZIKA/CHIK) was constructed with each polyprotein immunogen driven by the same synthetic strong early late promoter [ 20 ], but from two distinct distant loci from within the SCV genome [ 18 ]. A dual ZIKV and CHIKV vaccine was deemed attractive as these virus co-circulate in overlapping geographic regions, and can co-infect both mosquitoes and humans [ 21 – 23 ]. SCV-ZIKA/CHIK was shown to protect against CHIKV and ZIKV in a series of mouse models [ 18 ].…”