Journal of Vaccine Research 2024, Vol.14, No.2, 65-75 http://medscipublisher.com/index.php/jvr 70 to attack prostate cancer cells. The success of Provenge has paved the way for further research into the use of adjuvants in cancer vaccines, highlighting the importance of personalized immunotherapy in oncology (Li et al., 2022). 6.2 HPV vaccines (Cervarix, Gardasil) Cervarix and Gardasil are prophylactic vaccines designed to prevent infections by human papillomavirus (HPV), which is linked to cervical cancer and other HPV-related diseases. Both vaccines have shown high efficacy in inducing long-lasting immune responses. Cervarix, which contains the AS04 adjuvant, has been found to induce higher and more persistent antibody responses compared to Gardasil, which uses an aluminum-based adjuvant (Godi et al., 2019; Lehtinen et al., 2020; Nicoli et al., 2020). The AS04 adjuvant in Cervarix enhances the immune response by stimulating both the innate and adaptive immune systems, providing cross-protection against non-vaccine HPV types (Lehtinen et al., 2020; Matsumura et al., 2023) (Figure 2). Figure 2 Scientific evaluation of macrophagic myofasciitis (MFF) (Adopted from Matsumura et al., 2023) Image caption: Some vaccines contain aluminum (Al) hydroxide as an adjuvant, enhancing immune responses to antigens. Following intramuscular vaccination in the deltoid muscle, macrophages phagocytose Al-adsorbed antigens and present antigens to lymphocytes. (Top) Subsequently, the local inflammation induced by the vaccination is subsided, and macrophages and a few lymphocytes could be seen as scar or a “vaccination tattoo” in the deltoid muscle. (Middle) When autoimmune diseases or microbial infections occur, pro-inflammatory cytokine levels in sera can be increased, activating pre-existing infiltrated macrophages in the deltoid muscle in a bystander fashion (“bystander activation”); Al-containing activated macrophages can be observed as MMF pathology. Here, MMF is the result of systemic inflammation. (Bottom) Authier's group proposed that the vaccination with an Al-containing vaccine causes pathological inflammation composed of macrophages with Al in the cytoplasm in the deltoid muscle by, as yet, an unknown mechanism. Although MMF pathology is localized at the deltoid, this leads to diffuse myalgia at the upper and lower extremities, and sometimes can cause autoimmune diseases, such as multiple sclerosis by, as yet, an unknown mechanism. Here, MMF is the cause of autoimmune diseases (Adopted from Matsumura et al., 2023) 6.3 Experimental vaccines Experimental cancer vaccines are being developed to target various types of cancers using different adjuvants to enhance their efficacy. For instance, a study on a mannose receptor-targeting nano-adjuvant combined with a peptide vaccine showed promising results in a murine model of HPV-induced cervical cancer. This nano-adjuvant, which includes a toll-like receptor agonist, significantly improved antitumor immunity by targeting antigen-presenting cells and reducing immunosuppressive cells in the tumor microenvironment (Mohapatra et al., 2023). Another experimental approach involves the use of a black phosphorus nanosheet-based nanovaccine, which has demonstrated strong antigen-specific T-cell responses and antitumor effects in preclinical studies (Li et al., 2022). These innovative adjuvant strategies are crucial for the development of effective therapeutic cancer vaccines.
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