Journal of Vaccine Research, 2025, Vol.15, No.1, 34-44 http://medscipublisher.com/index.php/jvr 36 3 Immunology and Technical Fundamentals 3.1 Immune challenges Pathogens transmitted by viruses, protozoa and other insects have very different antigens, which makes the development of vaccines particularly difficult. The variety of surface proteins that cause different pathogens makes it difficult for a single vaccine to provide broad and long-lasting protection. Pathogens such as dengue virus, Zika virus and Plasmodium become and evolve rapidly and can evade the tracking of the human immune system, greatly reducing the efficacy of vaccines (Figure 1) (Kaufland, 2020; Wang et al., 2023; Tang et al., 2025). Figure 1 Schematic overview of immune response induction by viral vector vaccines (Adopted from Tang et al., 2025) Image caption: Viral vectors facilitate antigen delivery into host cells (top panel), leading to intracellular processing and presentation on MHC class I molecules, which activates cytotoxic CD8+T cells (bottom right); Antigens taken up by antigen-presenting cells (APCs) like macrophages are presented on MHC class II molecules, activating CD4+T helper cells; These helper cells provide signals (e.g., IL-2, IL-4, IL-5) that support B cell activation, proliferation, and differentiation into antibody-producing plasma cells (bottom left) (Adopted from Tang et al., 2025) Not only that, many vector-borne pathogens have also evolved complex ways to evade immune system attacks. They can inhibit the presentation of antigens, interfere with the body's immune response, and even survive for a long time in human tissues, all of which pose challenges to stimulating lasting and powerful immunity through vaccination. To solve these immunological problems, it is necessary to innovate vaccine design so that the vaccine can simultaneously stimulate humoral immunity and cellular immunity in the human body and effectively combat a wide variety of and constantly changing pathogen populations (Coughlan, 2020; Wang et al., 2023; Li, 2024). 3.2 Overview of the vaccine platform Nowadays, people are researching various vaccine technologies for vector-borne diseases. Each technology has its own advantages as well as some shortcomings. Inactivated vaccines and subunit vaccines are relatively traditional methods with guaranteed safety, but compared with new technologies, the immune response they trigger may not be as strong. Just as during the COVID-19 pandemic, mRNA vaccines have received extensive attention due to their advantages of fast development speed and the ability to stimulate a strong immune response (Kanokudom et al., 2021; Tang et al., 2025). Viral vector vaccines made from adenovirus and poxvirus have a very good effect in activating human immunity and are also very flexible to use. This type of vaccine can directly deliver substances carrying target antigen information into human cells, thereby activating cellular immunity and humoral immunity within the body. Recent
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