Abstract
Recombinant proteins are gaining enormous importance these days due to their wide application as biopharmaceutical products and proven safety record. Various recombinant proteins of therapeutic and prophylactic importance have been successfully produced in microbial and higher expression host systems. Since there is no specific antiviral therapy available against dengue, the prevention by vaccination is the mainstay in reducing the disease burden. Therefore, efficacious vaccines are needed to control the spread of dengue worldwide. Dengue is an emerging viral disease caused by any of dengue virus 1–4 serotypes that affects the human population around the globe. Dengue virus is a single stranded RNA virus encoding three structural proteins (capsid protein, pre-membrane protein, and envelope protein) and seven non-structural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5). As the only licensed dengue vaccine (Dengvaxia) is unable to confer balanced protection against all the serotypes, therefore various approaches for development of dengue vaccines including tetravalent live attenuated, inactivated, plasmid DNA, virus-vectored, virus-like particles, and recombinant subunit vaccines are being explored. These candidates are at different stages of vaccine development and have their own merits and demerits. The promising subunit vaccines are mainly based on envelope or its domain and non-structural proteins of dengue virus. These proteins have been produced in different hosts and are being investigated for development of a successful dengue vaccine. Novel immunogens have been designed employing various strategies like protein engineering and fusion of antigen with various immunostimulatory motif to work as self-adjuvant. Moreover, recombinant proteins can be formulated with novel adjuvants to enhance the immunogenicity and thus conferring better protection to the vaccinees. With the advent of newer and safer host systems, these recombinant proteins can be produced in a cost effective manner at large scale for vaccine studies. In this review, we summarize recent developments in recombinant protein based dengue vaccines that could lead to a good number of efficacious vaccine candidates for future human use and ultimately alternative dengue vaccine candidates.
Highlights
Dengue is a mosquito-borne viral infection caused by any of 1–4 serotypes of dengue virus
This study showed that a tetravalent E85-virus replicon particles (VRP) dengue vaccine elicited a simultaneous and protective response to dengue virus 1-4
A physical tetravalent mixture containing DIII and C protein of each dengue virus serotype (Tetra DIIIC) was evaluated in monkeys. This protein boosted neutralizing antibody responses previously generated in monkeys. These results suggested the potential use of a Tetra DIIIC as a dengue vaccine candidate [108]
Summary
Dengue is a mosquito-borne viral infection caused by any of 1–4 serotypes of dengue virus. An NS1 based DNA vaccine candidate (pcTPANS1) encoding the t-PA signal sequence linked to NS1 gene of dengue virus 2, elicited high antibody response and further provided protection in 97% mice from challenge with dengue virus 2, without producing neutralizing antibodies [70, 130]. A tetravalent dengue vaccine candidate based on a recombinant MV vector expressing EDIII of dengue virus 1 to 4 was constructed and immunized in mice.
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