Plant‐produced Zika virus envelope protein elicits neutralizing immune responses that correlate with protective immunity against Zika virus in mice

Abstract

Summary The global Zika virus (ZIKV) outbreak and its link to fetal and newborn microcephaly and severe neurological complications in adults call for the urgent development of ZIKV vaccines. In response, we developed a subunit vaccine based on the ZIKV envelope (E) protein and investigated its immunogenicity in mice. Transient expression of ZIKV E (zE) resulted in its rapid accumulation in leaves of Nicotiana benthamiana plants. Biochemical analysis revealed that plant-produced ZIKV E (PzE) exhibited specific binding to a panel of monoclonal antibodies that recognize various zE conformational epitopes. Furthermore, PzE can be purified to >90% homogeneity with a one-step Ni2+ affinity chromatography process. PzE are found to be highly immunogenic, as two doses of PzE elicited both potent zE-specific antibody and cellular immune responses in mice. The delivery of PzE with alum induced a mixed Th1/Th2 immune response, as the antigen-specific IgG isotypes were a mixture of high levels of IgG1/IgG2c and splenocyte cultures from immunized mice secreted significant levels of IFN-gamma, IL-4 and IL-6. Most importantly, the titers of zE-specific and neutralizing antibodies exceeded the threshold that correlates with protective immunity against multiple strains of ZIKV. Thus, our results demonstrated the feasibility of plant-produced ZIKV protein antigen as effective, safe and affordable vaccines against ZIKV.

DCL‐suppressed Nicotiana benthamiana plants: valuable tools in research and biotechnology

“…Heterologous protein expression in plants is an interesting choice for the overexpression of molecules for cosmetic, pharmaceutical or other uses (Pua et al , ; Rattanapisit et al , ; Yang et al , ). One important limiting factor in this approach remains the yield of the proteins produced (Desai et al , ; Kusnadi et al , ).…”

Expression of ESAT‐6 antigen from Mycobacterium tuberculosis in broccoli: An edible plant

“…Results of oral immunization using the raw plant biomass are of special interest because it is the most advantageous immunization strategy in terms of cost and easy application. Production of oral subunit vaccine against TB in edible plants is promising strategy to eliminate the expensive downstream processing, purification costs, maintenance of cold chain for transport and storage of vaccines, and need of sterile needles for injections . This will be helpful for poor countries where TB incidence is increasing day by day.…”

“…Due to safety issues of heat killed or whole cell antigen vaccines, production of plant‐based vaccines has become a striking strategy for the development of cost‐effective vaccines due to some important features such as: high scalability, low health risks, minimum need of cooling chain, and low cost of downstream processing . Currently, delivery of vaccines via plant systems has gained a high consideration platform for oral administration and its renowned potential to stimulate immunity in human and animals . The idea of edible vaccine refers to oral administration of antigens expressed in recombinant plants to stimulate the systematic and mucosal immunity against different pathogenic, bacterial, and viral diseases.…”

Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

“…The main antigenic determinant of the virus is the envelope glycoprotein (E), since it is displayed on the surface of the mature virus particle and can be targeted by a number of neutralizing antibodies [9,10]. Neutralizing antibodies generated by approved vaccines for yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus, which are closely related to ZIKV, appear to have a correlation with viral protection [11,12].…”