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Research paper
22
2025/12
Biodistribution and mechanisms of action of MF59 and MF59-like adjuvants.
In recent years, adjuvants—key components of vaccines—have attracted increasing attention. Nearly a century has passed since Gaston Roman first introduced the concept of adjuvants in 1925, during which time extensive preclinical and clinical research on vaccine adjuvants has been conducted. Nevertheless, to date only a handful of adjuvants have been successfully incorporated into licensed vaccines. This low rate of clinical translation is largely attributable to a lack of a comprehensive and mechanistically deep understanding of how adjuvants function within complex biological systems. Indeed, MF59 was the first non-aluminum adjuvant to be used in an approved human vaccine and remains in use today; yet many aspects of its mechanism of action remain poorly understood. Accordingly, this review examines the current state of knowledge regarding the mechanisms of action of MF59 and MF59-like adjuvants, drawing on evidence-based temporal and spatial processes underlying immunomodulatory events. In addition, it summarizes the key factors by which MF59 and MF59-like adjuvants modulate humoral and cellular immune responses. Furthermore, based on published studies, the review analyzes the distribution and clearance of antigens and adjuvants to gain deeper insights into the safety profile of MF59-adjuvanted vaccines. This review not only facilitates the development of novel squalene-based adjuvants and their prospects for clinical application but also provides valuable guidance for future mechanistic investigations of other vaccine adjuvants.
22
2025/12
Reactivation of varicella-zoster virus (VZV) leads to herpes zoster (HZ), which can cause complications such as postherpetic neuralgia. The commercially available subunit adjuvanted HZ vaccine, Shingrix®, provides substantial protection against HZ in older adults. However, the adjuvant system used in this vaccine has limitations, highlighting the need for alternative adjuvant platforms. In this study, we developed a novel adjuvant system, BK-02, based on ELISA, ELISpot, and flow cytometry analyses. This system comprises the Toll-like receptor 9 (TLR9) agonist BK-02C (CpG2006) and a squalene-based oil-in-water emulsion, BK-02M (MF59). Our results demonstrate that, when combined with the recombinant VZV vaccine’s major antigen, glycoprotein E (gE), the BK-02 adjuvant system elicits significantly higher gE-specific IFN-γ+ T cell responses—486 SFU per 10⁶ cells, 121-fold greater than with gE alone—and markedly elevated IgG antibody titers, with an IgG titer of 5.2 compared to 3.4 for gE alone. The optimal dose for inducing gE-protein–specific cellular immunity in mice was determined to be 5 μg gE plus 30 μg BK-02C and 1× BK-02M, which corresponds clinically to 50 μg gE, 300/500 μg BK-02C, and 0.5 mL BK-02M. Furthermore, scale-up samples of the recombinant VZV vaccine elicited stronger gE-specific CD4+ and CD8+ T cell immune responses than Shingrix®. In addition, the gE/BK-02 adjuvant system induces a Th1-skewed mixed immune response, thereby generating robust cellular and humoral immunity. These findings suggest that the BK-02 adjuvant system is a promising candidate for use as an adjuvant in current VZV subunit vaccines.
22
2025/12
The needle-free injection system (NFIS) is easy to use and can help reduce fear of needles. NFIS enables a more dispersed delivery, enhancing the interaction between antigens and local immune cells at the injection site, which may improve the immune response elicited by mRNA vaccines. Despite the remarkable success of SARS-CoV-2 mRNA vaccines, there remains an urgent need for universal vaccines. Delivery of a universal mRNA vaccine via NFIS represents the preferred approach for addressing COVID-19. We designed and synthesized RBD3-Fc mRNA encoding the BA.4, Delta, and prototype RBDs, along with an IgG Fc containing the YTE mutation. Using the needle-free injection system (NFIS, designated GV-01), we administered both naked RBD3-Fc mRNA and mRNA-LNP–based vaccines intradermally, as well as intramuscularly via a needle, and evaluated and compared their safety and immunogenicity in mice. A prime-boost vaccination regimen delivered via both routes induced robust immune responses, with intradermal administration demonstrating comparable or superior performance in terms of binding antibody, neutralizing antibody, and T-cell responses. Naked mRNA vaccines were functional but less effective than mRNA-LNP–based vaccines. These findings indicate that the RBD3-Fc vaccine is safe and immunogenic, and that the needle-free injection system can serve as a needle-and-syringe alternative for administering mRNA-LNP vaccines to elicit strong systemic immune responses.