Preparedness for the Dengue Epidemic: Vaccine as a Viable Approach

Abstract

Dengue fever is one of the significant fatal mosquito-borne viral diseases and is considered to be a worldwide problem. Aedes mosquito is responsible for transmitting various serotypes of dengue viruses to humans. Dengue incidence has developed prominently throughout the world in the last ten years. The exact number of dengue cases is underestimated, whereas plenty of cases are misdiagnosed as alternative febrile sicknesses. There is an estimation that about 390 million dengue cases occur annually. Dengue fever encompasses a wide range of clinical presentations, usually with undefinable clinical progression and outcome. The diagnosis of dengue depends on serology tests, molecular diagnostic methods, and antigen detection tests. The therapeutic approach relies completely on supplemental drugs, which is far from the real approach. Vaccines for dengue disease are in various stages of development. The commercial formulation Dengvaxia (CYD-TDV) is accessible and developed by Sanofi Pasteur. The vaccine candidate Dengvaxia was inefficient in liberating a stabilized immune reaction toward different serotypes (1-4) of dengue fever. Numerous promising vaccine candidates are now being developed in preclinical and clinical stages even though different serotypes of DENV exist that worsen the situation for a vaccine to be equally effective for all serotypes. Thus, the development of an efficient dengue fever vaccine candidate requires time. Effective dengue fever management can be a multidisciplinary challenge, involving international cooperation from diverse perspectives and expertise to resolve this global concern.

Keywords: Aedes mosquito; clinical presentations; dengue; dengue vaccines; diagnosis.

Figure 1

DENV and DENV serotype: The dengue virus is roughly spherical. Dengue infections are caused by four closely related viruses, named DENV-1, DENV-2, DENV-3, and DENV-4. An individual develops immunity to a specific dengue virus after recovering from an infection.

Figure 2

Classification of dengue disease: Dengue can range from an infection with no symptoms to a serious condition, as shown in the flowchart of Figure 2 (Note: classification based on WHO dengue guidelines—2009).

Figure 3

Clinical presentation of dengue infection and features: The clinical signs of dengue are outlined in the figure, as per classification based on WHO dengue guideline—2009. (Adapted from Dengue, Guidelines for Diagnosis, Treatment, Prevention and Control, WHO/TDR).

Figure 4

Pathogenesis of DENV: Released viral particles by mosquito bite may cause local immune cells to activate, primarily monocytes or dendritic cells (DCs). Natural killer (NK) cells and T cells are recruited because of a local inflammatory reaction to DENV in the skin, which enhances the death of virus-infected cells at the injection site. DENV will spread along the lymphatic pathways to draining lymph nodes, resulting in systemic infection.

Figure 5

Dengue vaccine platform: Vaccines against the dengue virus have been developed using a range of platforms and funded by private companies as well as government agencies.

Figure 6

Therapeutic mechanism of a dengue vaccine: Vaccine was administered subcutaneously, and antigen-presenting cells (APC) present the processed antigen, which stimulates T lymphocytes. T lymphocytes promote the development of B cells. The maturation of the antibody response occurs because of B-cell proliferation, which is dependent on the T cells. Neutralizing antibodies (Nabs) specific for the dengue vaccine are secreted preferentially by plasma cells. Activated CD8 T cells can mount a response against infection by secreting cytokines and killing off viral infected cells.