Aiming at the heart: the capsid protein of dengue virus as a vaccine candidate

ABSTRACT

Introduction: Dengue fever remains as a health problem worldwide. Although Dengvaxia®, was registered in several countries, the results after the immunization of people suggest an increase of risk in non-immune persons and children younger than 9 years old. No other vaccine is registered so far, thus the development of a safe and effective vaccine continues to be a priority for the WHO and the scientific community.

Areas covered: This work reviews the structural and antigenic properties of the capsid protein of Dengue virus, along with results of studies performed to assess the immunogenicity and protective capacity in animals of vaccine candidates based on this protein.

Expert opinion: The generation of a memory cellular immune response alone, after vaccination against Dengue virus, could be advantageous, as there would not be risk of increasing viral infectivity through sub-neutralizing antibodies. However, it is improbable to achieving sterilizing immunity. In this scenario, an infection could stablished but without the appearance of the severe disease. The cell-mediated immunity should keep the virus at bay. The capsid protein induces a protective immune response in animals without the induction of virus-binding antibodies. Vaccine candidates based on this protein could be an attractive strategy to induce protection against the severe Dengue disease.

KEYWORDS:

• Dengue
• capsid
• recombinant protein
• vaccine
• cell-mediated immunity

Article highlights

• The capsid protein is the main target for CD4 + T cells against dengue virus.

• The immunization of mice with recombinant capsid proteins from the four dengue virus serotypes expressed in E. coli, induce protective immune responses without the induction of antiviral antibodies.

• The tetravalent formulation composed of the four recombinant capsid proteins significantly reduces the viral load in immunized monkeys.

• A vaccine candidate against dengue virus based only on the induction of CMI will avoid the antibody-dependent enhancement phenomenon.

• This box summarizes key points contained in the article.

Declaration of interest

All authors of this paper disclose working for the Center for Genetic Engineering and Biotechnology (CIGB). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The work was supported by the Center for Genetic Engineering and Biotechnology (CIGB).