Journal of Mosquito Research, 2024, Vol.14, No.5, 264-275 http://emtoscipublisher.com/index.php/jmr 265 challenges in vaccine supply and innovations in development, and identify future directions for optimizing global YF control efforts, with a particular focus on initiatives like the EYE strategy to mitigate outbreak risks and meet the needs of at-risk populations. 2 Current Vaccine Strategies for Yellow Fever Yellow Fever (YF) remains a critical public health issue in many tropical regions, and vaccination is the primary method for preventing outbreaks. Various vaccination strategies, including live-attenuated, inactivated, recombinant, and vector-based approaches, have been developed and evaluated over the years. Each of these strategies has distinct mechanisms, benefits, and challenges. This section delves into these strategies and explores their role in current and future yellow fever control efforts. 2.1 Live-attenuated vaccines: mechanism and effectiveness The 17D live-attenuated yellow fever vaccine is considered the gold standard for YF prevention and has been in use since its development in the 1930s. This vaccine is derived from an attenuated strain of the yellow fever virus, which has been modified to reduce its virulence while retaining its ability to elicit a robust immune response. The mechanism behind its effectiveness lies in its ability to mimic a natural infection, leading to the activation of both the humoral and cellular arms of the immune system. Upon administration, the vaccine stimulates the production of high titers of neutralizing antibodies, providing immunity that is often lifelong after a single dose (Beck and Barrett, 2015). One of the primary advantages of the 17D vaccine is its long-term efficacy, which has been shown to last for decades in most vaccinated individuals. The World Health Organization (WHO) has recommended a single dose of the vaccine as sufficient for lifelong protection, a significant benefit for resource-limited settings where booster programs may be challenging to implement (Chen and Wilson, 2020). However, the 17D vaccine is not without risks. Rare but severe adverse events, such as Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD) and Neurotropic Disease (YEL-AND), have been reported, particularly in older adults, immunocompromised individuals, and those with thymus disorders (Wang et al., 2022). The need to mitigate these risks has spurred research into alternative formulations and delivery methods, such as fractional dosing, which has been employed during vaccine shortages. Fractional doses, which are smaller than the standard dose, have been shown to elicit similar immune responses, thus providing a temporary solution during periods of high demand (Nnaji et al., 2019). Nevertheless, the live-attenuated 17D vaccine remains the cornerstone of YF prevention, with ongoing efforts to enhance its safety profile and ensure adequate supply. 2.2 Inactivated vaccines: development and limitations Inactivated yellow fever vaccines present an alternative approach aimed at overcoming the limitations associated with live-attenuated vaccines, particularly concerning safety. These vaccines use a killed form of the virus, which means they cannot replicate in the host, making them safer for use in immunocompromised individuals and those with contraindications to live vaccines. The development process involves cultivating the yellow fever virus in Vero cells, followed by inactivation using agents such as β-propiolactone. This approach ensures that the vaccine retains its immunogenic components while eliminating its ability to cause disease (Yang, 2024). Recent studies have demonstrated that inactivated vaccines can induce robust immune responses, with high levels of neutralizing antibodies in animal models, comparable to those elicited by live-attenuated vaccines (Bassi et al., 2016). For instance, research using inactivated YF vaccines in mice has shown promising results, suggesting that these vaccines could provide an effective alternative to the 17D vaccine in populations where live vaccines pose a higher risk. However, inactivated vaccines also have their limitations. They often require multiple doses or booster shots to achieve and maintain sufficient immunity, which can be challenging in regions with limited access to healthcare services. Additionally, the production process for inactivated vaccines can be more complex and expensive, which may hinder their widespread use, especially in low-income countries where yellow fever is endemic. Despite these
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