Recent Developments in Recombinant Protein–Based Dengue Vaccines

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.

A Review on Dengue Vaccine Development

“…Recombinant subunit vaccines are antigenic proteins expressed by prokaryotic or eukaryotic cells to stimulate long-lasting protective/therapeutic immune responses [54][55][56]. Expression of the recombinant dengue proteins in E. coli is relatively easy, but meanwhile, there are some problems of endotoxin contamination and improper protein folding [57].…”

The Interplay between Dengue Virus and the Human Innate Immune System: A Game of Hide and Seek

“…Multiple tetravalent vaccine candidates are being developed. These include live-attenuated vaccines, whole virus inactivated vaccines, protein-based vaccines, chimeric vaccines, and mRNA-based and synthetic virus-like particle vaccines [137][138][139][140][141][142]. Among these vaccines, Dengvaxia (also called CYD-TDV), developed by Sanofi Pasteur, is the only one licensed for use in about 20 dengue-endemic countries in Asia, Latin America, and Oceania as well as in Europe.…”

Addition of Partial Envelope Domain II into Envelope Domain III of Dengue Virus Antigen Potentiates the Induction of Virus-Neutralizing Antibodies and Induces Protective Immunity

“…One such alternative is a recombinant protein antigen (Ag)-based subunit vaccine. Subunit vaccines are typically safer than attenuated virus vaccines and are capable of inducing an immune response against the four DENV serotypes [14][15][16]. A subunit vaccine with restricted epitopes can be used to reduce unwanted Ab production, which is not involved in virus neutralization, and so prevents ADE [17,18].…”

“…The leading subunit vaccine candidate is V180, which was developed by Merck and consists of recombinant carboxyl-truncated E proteins (DEN-80E) of the four DENV serotypes. It induces a high titer of neutralizing Abs and provides protection against the four DENV serotypes in mice and rhesus monkeys [14]. Additionally, because EDIII contains the receptor-binding site, its suitability as a vaccine antigen has been investigated [20].…”