Journal of Mosquito Research, 2024, Vol.14, No.5, 264-275 http://emtoscipublisher.com/index.php/jmr 266 challenges, ongoing research is focused on optimizing inactivation methods and adjuvant formulations to enhance the efficacy and durability of the immune response, making inactivated vaccines a viable option for future yellow fever control efforts. 2.3 Recombinant and subunit vaccines: emerging approaches Recombinant and subunit vaccines represent a newer generation of vaccines that offer several advantages over traditional methods, particularly in terms of safety and production scalability. These vaccines utilize specific proteins or antigens from the yellow fever virus to stimulate an immune response without the need for a live virus. A notable example is the use of the yellow fever virus envelope protein (YFE), which has been expressed in plant systems like Nicotiana benthamiana. This approach has shown the potential to induce strong virus-neutralizing antibody responses in preclinical studies involving mice and non-human primates (Tottey et al., 2017; Shou and Cai, 2024). One key advantage of recombinant and subunit vaccines is their safety profile, as they do not contain live components and thus eliminate the risk of vaccine-induced disease. This makes them particularly suitable for use in populations that are more vulnerable to the adverse effects of live vaccines, such as the elderly, pregnant women, and immunocompromised individuals. Additionally, production using recombinant technology can be scaled more easily than traditional egg-based methods, making it a promising solution for meeting global demand during outbreaks. Despite these benefits, recombinant and subunit vaccines for yellow fever are still largely in the experimental stage, and their immunogenicity tends to be lower compared to live-attenuated vaccines. This often necessitates the use of adjuvants to boost the immune response, which can add complexity to vaccine formulations. Moreover, ensuring that these vaccines elicit a balanced immune response capable of providing durable protection remains a critical challenge. Ongoing research aims to address these issues, with a focus on improving the stability and potency of recombinant vaccines, making them a potential candidate for widespread use in the future. 2.4 Vector-based vaccines: novel concepts and preclinical research Vector-based vaccines use a viral or bacterial vector to deliver yellow fever antigens into the host cells, where they stimulate an immune response. This strategy is particularly appealing because it can combine the strong immunogenicity of live vaccines with the safety profile of non-replicating systems. Modified vaccinia virus Ankara (MVA) and replication-deficient adenoviruses are among the most promising platforms for vector-based yellow fever vaccines. These vectors can be engineered to express yellow fever virus antigens, leading to the production of neutralizing antibodies and T-cell responses similar to those seen with live-attenuated vaccines (Bassi et al., 2016). The MVA-based yellow fever vaccine, for example, has been shown to generate a protective immune response in animal models, with levels of neutralizing antibodies comparable to those induced by the 17D vaccine. This vector-based vaccine also demonstrated improved safety, with no replication in the host, making it a potentially safer alternative for those at higher risk of adverse reactions to live vaccines (Julander et al., 2018). Additionally, vector-based vaccines allow for rapid development and production, which is crucial during sudden outbreaks when time is of the essence. The flexibility of vector-based systems also opens up possibilities for creating combination vaccines that protect against multiple pathogens, potentially providing a broader public health benefit. However, the development of vector-based vaccines faces challenges, such as pre-existing immunity to the vector itself, which can reduce the vaccine's effectiveness. Addressing these challenges through the use of novel vector systems and exploring non-viral delivery methods are active areas of research, positioning vector-based vaccines as a promising direction for future yellow fever vaccination strategies. 3 Challenges and Limitations in Yellow Fever Vaccination Yellow fever (YF) vaccination has proven to be an effective tool in controlling outbreaks and preventing the spread of this potentially deadly disease. However, several challenges persist, including vaccine shortages, safety
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