A Recombinant Subunit Based Zika Virus Vaccine Is Efficacious in Non-human Primates

Abstract

Zika Virus (ZIKV), a virus with no severe clinical symptoms or sequelae previously associated with human infection, became a public health threat following an epidemic in French Polynesia 2013–2014 that resulted in neurological complications associated with infection. Although no treatment currently exists, several vaccines using different platforms are in clinical development. These include nucleic acid vaccines based on the prM-E protein from the virus and purified formalin-inactivated ZIKV vaccines (ZPIV) which are in Phase 1/2 clinical trials. Using a recombinant subunit platform consisting of antigens produced in Drosophila melanogaster S2 cells, we have previously shown seroconversion and protection against viremia in an immunocompetent mouse model. Here we demonstrate the efficacy of our recombinant subunits in a non-human primate (NHP) viremia model. High neutralizing antibody titers were seen in all protected macaques and passive transfer demonstrated that plasma from these NHPs was sufficient to protect against viremia in mice subsequently infected with ZIKV. Taken together our data demonstrate the immunogenicity and protective efficacy of the recombinant subunit vaccine candidate in NHPs as well as highlight the importance of neutralizing antibodies in protection against ZIKV infection and their potential implication as a correlate of protection.

Defeat Dengue and Zika Viruses With a One-Two Punch of Vaccine and Vector Blockade

“…Besides, other forms of ZIKV vaccine, such as protein based subunit vaccine (Medina et al, 2018;Metz et al, 2019;Slon-Campos et al, 2019) and live attenuated Zika vaccines (Richner et al, 2017b;Xie et al, 2018;Shan et al, 2019) are also under development at the pre-clinical stage. Considering the crossreactivity and ADE between ZIKV and DENV, newly developed ZIKV vaccine should also be tested for DENV enhancement activity.…”

“…Because ZIKV and DENV have different pathogenic characteristics and tropism, special issues should be considered during the development of vaccines to these viruses, especially for prophylactic ZIKV vaccines which are currently under development by several research groups (Richner et al, 2017b;Tebas et al, 2017;Medina et al, 2018;Modjarrad et al, 2018;Zou et al, 2018).…”

Inactivation of Zika Virus by Photoactive Iodonaphthyl Azide Preserves Immunogenic Potential of the Virus

“…Therefore, effective prophylactic measures are needed to counter these potential outbreaks of ZIKV. Several candidates of ZIKV vaccine are in development, but to date none have received FDA approval or licensure [8][9][10][11][12]. In this study, we describe inactivation of ZIKV using the photoactive hydrophobic compound INA.…”

Characterization of a Species E Adenovirus Vector as a Zika virus vaccine

“…Since the 2015/16 Zika virus (ZIKV) outbreak in Brazil, there has been continued progress towards the development of a safe and efficacious vaccine. Many vaccine platforms have been explored in pre-clinical studies, such as live attenuated [1][2][3] , inactivated 4,5 , subunit 6,7 , DNA [8][9][10] , mRNA 11,12 , and viral vectors 13,14 . Phase I clinical trials have been completed using a purified inactivated virus 5 and DNA plasmids expressing the ZIKV prM-E genes 10,15 and have shown mild to moderate adverse events with promising seroconversion rates 5,10,15 .…”