Recent advances on coxsackievirus A6 vaccine research

Figures

• 

  Figure 1. Diagram of main pathways of viral vaccine development and mouse model-based pre-clinical evaluation. Multiple technology pathways of viral vaccines (not limited to the diagram) play a key role in eradication of infectious diseases such as smallpox and polio. Vaccine assessment is a crucial process to evaluate the efficiency and safety. Cell culture provides strain isolation and clone, while animal models serve for evaluation of pathogenicity, immune response and protection.

• 

  Figure 2. Diagram of CVA6 genome structure. The genome (~7400bp) is translated to produce polyproteins P1-P3. The P1 region encodes four structural proteins VP1-VP4, while the P2/P3 region encodes seven non-structural proteins, including 2A-2C and 3A-3D. The viral genome is covalently linked to the viral protein VPg (3B), which is required as a primer for replication. Genome translation yields a single polyprotein, which is subsequently proteolytically cleaved into two distinct groups of proteins. The first group consists of the replication proteins (2A–2C and 3A–3D), while the second group comprises the capsid proteins (VP0, VP1, and VP3). The maturation process of the virus involves the synthesis of three structural proteins (VP0, VP1, VP3) in the P1 region of the CVA6 virus, followed by the cleavage of VP0 into VP2 and VP4 to form a complete capsid protein. The process of genome replication by the viral RNA-dependent RNA polymerase (3Dpol) commences with the synthesis of a negative-strand (–) RNA molecule that functions as a template for the subsequent synthesis of new (+) RNA molecules. Replication occurs within membranous replication organelles, where a conducive lipid environment is…

• 

  Figure 3. Maximum clade credibility (MCC) tree of 309 representative VP1 sequences (915bp) of CVA6 strains worldwide. MCC tree was constructed using TreeAnnotator, and the burn-in option was used to remove the first 10% of the sampled trees; the resulting tree was visualized using FigTree (v1.4.4). The Markov chain Monte Carlo (MCMC) method implemented in BEAST (v1.8.4) was used to estimate the divergence time, temporal phylogenies and rates of evolution. Blue line: Bayesian skyline plots of viral relative genetic diversity; The light blue shadow: 95% CI.

• 

  Figure 4. Vaccine development process of different vaccine platforms. Major steps from vaccine design to in vivo evaluation were displayed. The purification process entails the use of sucrose gradient centrifugation, while the observation of structure involves the utilization of electron microscopy. The inactivation process was predominantly achieved through the use of formaldehyde or 56°C for 30 minutes.

• 

  Figure 5. Comparative analysis of CVA6 vaccines of different technology. The application potential and safety for each vaccine were comprehensive assessed by the accumulating evidence. These discourses, however, do not necessarily represent the final path to clinical translation of CVA6 vaccine.

• 

  Figure 6. Roadmap for actionable priorities for future CVA6 vaccine development. International collaborative efforts should be focused on global genome data sharing, comprehensive vaccine platform comparison, efficient animal models and scientific clinical trials.