DNA Vaccines: History, Molecular Mechanisms and Future Perspectives.

The history of DNA vaccine began as early as the 1960s with the discovery that naked DNA can transfect mammalian cells in vivo. In 1992, the evidence that such transfection could lead to the generation of antigen-specific antibody responses was obtained and supported the development of this technology as a novel vaccine platform. The technology then attracted immense interest and high hopes in vaccinology, as evidence of high immunogenicity and protection against virulent challenges accumulated from several animal models for several diseases. In particular, the capacity to induce T-cell responses was unprecedented in non-live vaccines. However, the technology suffered its major knock when the success in animals failed to translate to humans, where DNA vaccine candidates were shown to be safe but remained poorly immunogenic, or not associated with clinical benefit. Thanks to a thorough exploration of the molecular mechanisms of action of these vaccines, an impressive range of approaches have been and are currently being explored to overcome this major challenge. Despite limited success so far in humans as compared with later genetic vaccine technologies such as viral vectors and mRNA, DNA vaccines are not yet optimised for human use and may still realise their potential.

Chikungunya Virus: Priority Pathogen or Passing Trend?

Chikungunya virus (CHIKV) is considered a priority pathogen and a major threat to global health. While CHIKV infections may be asymptomatic, symptomatic patients can develop chikungunya fever (CHIKF) characterized by severe arthralgia which often transitions into incapacitating arthritis that could last for years and lead to significant loss in health-related quality of life. Yet, Chikungunya fever (CHIKF) remains a neglected tropical disease due to its complex epidemiology and the misrepresentation of its incidence and disease burden worldwide. Transmitted to humans by infected Aedes mosquitoes, CHIKV has dramatically expanded its geographic distribution to over 100 countries, causing large-scale outbreaks around the world and putting more than half of the population of the world at risk of infection. More than 50 years have passed since the first CHIKV vaccine was reported to be in development. Despite this, there is no licensed vaccine or antiviral treatments against CHIKV to date. In this review, we highlight the clinical relevance of developing chikungunya vaccines by discussing the poor understanding of long-term disease burden in CHIKV endemic countries, the complexity of CHIKV epidemiological surveillance, and emphasising the impact of the global emergence of CHIKV infections. Additionally, our review focuses on the recent progress of chikungunya vaccines in development, providing insight into the most advanced vaccine candidates in the pipeline and the potential implications of their roll-out.

Re-thinking yellow fever vaccines: fighting old foes with new generation vaccines.

Despite the existence of a highly efficient yellow fever vaccine, yellow fever reemergence throughout Africa and the Americas has put 900 million people in 47 countries at risk of contracting the disease. Although the vaccine has been key to controlling yellow fever epidemics, its live-attenuated nature comes with a range of contraindications that prompts advising against its administration to pregnant and lactating women, immunocompromised individuals, and those with hypersensitivity to chicken egg proteins. Additionally, large outbreaks have highlighted problems with insufficient vaccine supply, whereby manufacturers rely on slow traditional manufacturing processes that prevent them from ramping up production. These limitations have contributed to an inadequate control of yellow fever and have favored the pursuit of novel yellow fever vaccine candidates that aim to circumvent the licensed vaccine's restrictions. Here, we review the live-attenuated vaccine's limitations and explore the epitome of a yellow fever vaccine, whilst scrutinizing next-generation vaccine candidates.