Preparedness for the Dengue Epidemic: Vaccine as a Viable Approach

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

BA9 lineage of respiratory syncytial virus from across the globe and its evolutionary dynamics

<div><p>Respiratory syncytial virus (RSV) is an important pathogen of global significance. The BA9 is one of the most predominant lineages of the BA genotype of group B RSV that has acquired a 60bp duplication in its G protein gene. We describe the local and global evolutionary dynamics of the second hyper variable region in the C- terminal of the G protein gene of the BA9 lineage. A total of 418 sequences (including 31 study and 387 GenBank strains) from 29 different countries were used for phylogenetic analysis. This analysis showed that the study strains clustered with BA (BA9 and BA8) and SAB4 genotype of group B RSV. We performed time-scaled evolutionary clock analyses using Bayesian Markov chain Monte Carlo methods. We also carried out glycosylation, selection pressure, mutational, entropy and Network analyses of the BA9 lineage. The time to the most recent common ancestor (tMRCA) of the BA genotype and BA9 lineage were estimated to be the years 1995 (95% HPD; 1987–1997) and 2000 (95% HPD; 1998–2001), respectively. The nucleotide substitution rate of the BA genotype [(4.58×10⁻³ (95% HPD; 3.89–5.29×10⁻³) substitution/site/year] was slightly faster than the BA9 lineage [4.03×10⁻³ (95% HPD; 4.65–5.2492×10⁻³)]. The BA9 lineage was categorized into 3 sub lineages (I, II and III) based on the Bayesian and Network analyses. The local transmission pattern suggested that BA9 is the predominant lineage of BA viruses that has been circulating in India since 2002 though showing fluctuations in its effective population size. The BA9 lineage established its global distribution with report from 23 different countries over the past 16 years. The present study augments our understanding of RSV infection, its epidemiological dynamics warranting steps towards its overall global surveillance.</p></div

Global amino acid variability of the 2^nd HVR of G gene of BA9 lineage is represented by Shannon entropy plot.

<p>BioEdit software was used for calculation of entropy values of every amino acid at a particular position. Entropy values <0.2 were considered conserved whereas amino acids with >0.2 values are considered variable. High entropy value showed maximum variability at that particular position.</p

Estimated mean evolutionary rate and tMRCA of group B RSV.

<p>Estimated mean evolutionary rate and tMRCA of group B RSV.</p

Neighbor-joining phylogenetic tree of the 2^nd HVR of G gene of group B RSV; the tree was constructed using Kimura-2 parameter with 1,000 bootstrapping replicates.

<p>Only bootstrap values greater than 70% are shown at the branch nodes. The genotypes are indicated at the right by brackets. Prototype strains (M17213/USA/62) were used as an out-group. The study sequences are indicated by solid colored triangles.</p

Positively selected amino acid positions of the BA9 lineage.

<p>Positively selected amino acid positions of the BA9 lineage.</p

Amino acid mutations identified in positively selected sites of the BA9 lineage.

<p>Amino acid mutations identified in positively selected sites of the BA9 lineage.</p

Graphical representation of worldwide distribution of BA9 lineage of group B RSV; Color code bar in left side of the figure is used to represent the countries.

<p>The free available editable world map was downloaded from <a href="http://www.powerpointslides.net/fileadmin/user_upload/worldmap.ppt" target="_blank">http://www.powerpointslides.net</a> (<a href="http://www.powerpointslides.net/powerpointgraphics/powerpointmaps.html" target="_blank">http://www.powerpointslides.net/powerpointgraphics/powerpointmaps.html</a>). The map was created with PowerPoint and Adobe Photoshop.</p

Median joining network of the 2^nd HVR of G gene of group B depicting the relationship between the strains or lineages.

<p>The length of line between the haplotypes does not depend on the number of mutations. Each circle represents the haplotypes and surface area of each circle reflects the frequency. Haplotypes circulating in different countries were represented by colour-codes. Coloured segments inside the circle indicate the shared haplotypes. Median vectors are indicated by red circles.</p