Abstract
BackgroundThe incidence of dengue, an infectious disease caused by dengue virus (DENV), has dramatically increased around the world in recent decades and is becoming a severe public health threat. However, there is currently no specific treatment for dengue fever, and licensed vaccine against dengue is not available. Vaccination with virus-like particles (VLPs) has shown considerable promise for many viral diseases, but the effect of DENV VLPs to induce specific immune responses has not been adequately investigated.ResultsBy optimizing the expression plasmids, recombinant VLPs of four antigenically different DENV serotypes DENV1-4 were successfully produced in 293T cells. The vaccination effect of dengue VLPs in mice showed that monovalent VLPs of each serotype stimulated specific IgG responses and potent neutralizing antibodies against homotypic virus. Tetravalent VLPs efficiently enhanced specific IgG and neutralizing antibodies against all four serotypes of DENV. Moreover, vaccination with monovalent or tetravalent VLPs resulted in the induction of specific cytotoxic T cell responses.ConclusionsMammalian cell expressed dengue VLPs are capable to induce VLP-specific humoral and cellular immune responses in mice, and being a promising subunit vaccine candidate for prevention of dengue virus infection.
Highlights
The incidence of dengue, an infectious disease caused by dengue virus (DENV), has dramatically increased around the world in recent decades and is becoming a severe public health threat
The results showed that monovalent virus-like particles (VLPs) of each serotype could stimulate specific IgG and neutralizing antibody against homotypic virus, and tetravalent VLPs could induce specific IgG and neutralizing antibodies against all four serotypes of dengue virus
Production of DENV VLPs To optimize the production of DENV VLPs, three types of expression plasmids encoding prM and E glycoproteins were constructed for each serotype (Figure 1A)
Summary
The incidence of dengue, an infectious disease caused by dengue virus (DENV), has dramatically increased around the world in recent decades and is becoming a severe public health threat. One major reason is the phenomenon of antibody dependent-enhancement (ADE), which is known as that a subsequent infection with an alternate serotype can enhance severity of dengue disease [1]. One explanation of this phenomenon is that pre-existing non-neutralizing antibodies may enhance capacity of the new infecting DENV to access FcgR bearing cells. One example is the Sanofi Pasteur’s dengue vaccine candidate, which is based on a backbone of yellow fever vaccine (YF 17D) replication genes and incorporates the envelope genes of the four dengue virus serotypes, entered its final stage of clinical development in Australia. An ideal dengue vaccine should induce neutralizing antibody responses against all four serotypes simultaneously and it must be safe to use
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