language
Research paper
22
2025/12
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease, particularly among infants, older adults, and immunocompromised individuals. To date, no commercially available RSV vaccine has been approved. Importantly, formalin-inactivated RSV vaccines have been associated with enhanced respiratory disease. The pre-fusion conformation of the RSV fusion (F) protein represents a promising subunit vaccine candidate. However, several challenges remain, including low immunogenicity and a bias toward humoral immunity. Adjuvants can effectively enhance and modulate vaccine-induced immune responses. In this study, we formulated the pre-fusion RSV-F protein with the adjuvants Alhydrogel, MF59, AS03, AS02, and glucopyranosyl lipid (GCS). We then conducted a head-to-head comparison of vaccine-induced immune responses in BALB/c mice. All adjuvanted formulations boosted antigen-specific neutralizing antibody titers and viral clearance capacity, with the following order of adjuvant efficacy: AS02 > AS03, MF59 > GCS, and Alhydrogel. Notably, AS02 elicited the highest antibody levels, which persisted through week 18. Furthermore, AS02 significantly enhanced Th1-type immune responses in vaccinated mice. Mice in the AS02 group also exhibited faster recovery from viral challenge. Additional transcriptomic analysis revealed that AS02 modulates immune homeostasis by activating TLR-4 and promoting Th1-type responses. These findings suggest that AS02 may be an optimal adjuvant for RSV-F subunit vaccines. This study also provides valuable insights into the effects of other adjuvants on the immune response to RSV-F subunit vaccines.
22
2025/12
The development of vaccines using modified messenger RNA (mRNA) technology has demonstrated remarkable efficacy in combating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans. However, viral evolution in both human and non-human hosts—driven by the emergence of new variants with potent immune-evasion capabilities—may compromise vaccine performance. Consequently, there is an urgent need for a novel COVID-19 vaccine that can elicit high levels of broadly neutralizing antibodies (bnAbs) and rapidly adapt to viral mutations. Here, we have designed a bivalent mRNA vaccine, RBDco, which is based on chimeric receptor-binding domains (RBDs) derived from the spike (S) proteins of concern variants (VOCs) spanning multiple lineages and fused to Fc fragments. In mice and nonhuman primates, RBDco effectively induces neutralizing antibodies against a broad panel of pseudoviruses, including those representing potential circulating variants such as XBB.1, XBB.1.9.1, and EA.1. In mice, RBDco elicits neutralizing antibodies against 11 SARS-CoV-2 variant pseudoviruses spanning diverse lineages, with neutralizing antibody titers of 19,666 against the ancestral D614G strain and 13,274 against the circulating variant XBB.1.16. Moreover, RBDco stimulates IFN-γ production in mice in response to stimulation by RBD proteins from SARS-CoV-2 variants. In a mouse challenge model, treatment with RBDco reduces viral load in the lungs of challenged mice by tenfold. These findings demonstrate that RBDco can induce broad-spectrum neutralizing and cellular immune responses in animals, thereby preventing COVID-19. Furthermore, sequential immunization studies reveal that the RBDco booster group exhibits higher neutralizing antibody titers compared with the inactivated-vaccine group, along with enhanced memory T-cell differentiation. Overall, RBDco, by presenting chimeric RBDs that bind to SARS-CoV-2 variants across multiple lineages, can elicit broad-spectrum neutralizing antibodies in animals and represents a promising mRNA vaccine candidate capable of rapidly adapting to viral mutations.
22
2025/12
Herpes zoster (HZ) is a recurrent neurotropic infection caused by the reactivation of varicella-zoster virus (VZV). Currently, two commercially available vaccines for HZ are on the market: the live attenuated vaccine Zostavax™ and the AS01B-adjuvanted recombinant subunit vaccine Shingrix™. The latter demonstrates superior efficacy and longer-lasting immune persistence in older adults compared with the former. In this study, we used glycoprotein E (gE) as the antigen to investigate the effects of different adjuvants—MF59, MF59/CpG 2006, and MF59/QS-21—on the immune response in C57BL/6J mice, with the aim of identifying an alternative to the liposome/QS-21/MPL–based AS01B-like adjuvant. In addition to assessing safety, we measured gE-specific antibodies, IgG antibody subclasses, and cytokine production by splenocytes, as well as cell-mediated immune responses, using ELISA and ELISPOT assays. Our results showed that mice vaccinated with PBS or with any of the adjuvanted vaccines exhibited no significant changes in body weight, body temperature, or behavior. On day 28 after the first vaccination, all adjuvanted vaccine groups displayed significantly higher levels of gE-specific IgG antibodies than the group receiving gE alone. Moreover, all adjuvants markedly increased the levels of IgG1 and IgG2b. Notably, MF59/QS-21 and MF59/CpG 2006 were comparable to liposome/QS-21/MPL in enhancing IgG2c levels, both outperforming MF59. Further analysis revealed that MF59 elicited only modest increases in Th1 and Th2 cytokine levels, whereas MF59/QS-21, MF59/CpG 2006, and liposome/QS-21/MPL significantly boosted the secretion of interferon-γ (IFN-γ), IL-2, IL-4, and IL-10, resulting in a Th1-biased immune response. Additionally, the MF59/QS-21, MF59/CpG 2006, and liposome/QS-21/MPL adjuvanted vaccines induced comparable gE-specific IFN-γ–producing immune cell responses. These findings suggest that a combination of MF59 with QS-21 or CpG 2006 may serve as a promising adjuvant for subunit HZ vaccines. Further studies are needed to clarify its durability and efficacy in aged mice.
22
2025/12
Panax ginseng C.A. Meyer is a shade-loving plant, and its leaves are the principal medicinal part. Light intensity plays a critical role in the physiological activities and metabolite accumulation of P. ginseng. However, the molecular mechanisms underlying the physiological changes and quality attributes of ginseng leaves under different light intensities remain poorly understood. Therefore, we investigated the photosynthetic physiology, secondary metabolism, transcriptomics, and metabolomics of ginseng leaves exposed to three distinct light regimes: T20 (20 µmol m⁻²·s⁻¹), T50 (50 µmol m⁻²·s⁻¹), and T100 (100 µmol m⁻²·s⁻¹). Higher light intensity had a positive effect on leaf yield, photosynthetic performance, and the accumulation of polysaccharides, soluble sugars, terpenoids, and saponins. Notably, T100 treatment significantly enhanced saponin accumulation, with total saponins increasing by 68.32% and 45.55% compared with T20 and T50 treatments, respectively. The individual saponins Rg1, Re, Rb1, Rc, Rg2, Rb2, Rb3, and Rd increased 1.28-fold, 1.47-fold, 2.32-fold, 1.64-fold, 1.28-fold, 2.59-fold, 1.66-fold, and 2.28-fold, respectively, relative to the T20 treatment group. Furthermore, a total of 285 differentially accumulated metabolites (DAMs) and 4,218 differentially expressed genes (DEGs) were identified in the leaf metabolome and transcriptome, respectively. Among these, 13 triterpenoid saponins were markedly upregulated, while 3 were downregulated. Under T100 treatment, the expression of genes encoding photosystem II reaction-center proteins was upregulated, thereby enhancing photosynthetic activity. T100 also boosted the expression of genes involved in photosynthetic carbon and energy metabolism. In contrast, under T20 treatment, the expression of genes responsible for antenna protein synthesis was upregulated, increasing the leaf’s capacity to capture light. Moreover, T100 upregulated the expression of HMGR, SS, CYP716A53v2, UGT74AE, PgUGT1, and UGTPg45, thereby promoting the biosynthesis of terpenoids and saponins. In summary, a light intensity of 100 µmol m⁻²·s⁻¹ is conducive to the development of high-quality ginseng leaves. This study elucidates the molecular mechanisms underlying ginseng’s photosynthetic physiology and saponin biosynthesis, providing a theoretical foundation for the cultivation of P. ginseng and the industrial production of its secondary metabolites.
22
2025/12
We previously explored a series of adjuvant formulations containing prefusion RSV-F protein and found that AS02 may be a promising candidate adjuvant for developing RSV-F subunit vaccines with enhanced immunogenicity and an optimal immune response profile. In the present study, we compared the effects of intramuscular versus subcutaneous administration of a recombinant RSV-F subunit vaccine—formulated with or without the adjuvants Alhydrogel, squalene-based emulsion MF59, AS03, and AS02—on immune responses and protective efficacy in BALB/c mice. Following vaccination, we assessed antigen-specific antibodies, neutralizing antibodies, antibody subclasses, cytokine profiles, and the durability of the immune response. In addition, challenge experiments were conducted to evaluate the potential impact of vaccination route and adjuvant on viral clearance in the lungs and histopathological changes in mouse lung tissue. The results demonstrated that intramuscular injection is a more effective and antigen-sparing route that enhances immune responses, although subcutaneous administration elicits faster and stronger IgG antibody responses after primary immunization. Furthermore, adjuvants—not the route of immunization—are the more critical determinants of humoral and cellular immune responses as well as immune bias. Moreover, intramuscular administration of adjuvanted vaccines is safer than subcutaneous administration, particularly when using AS02. This study underscores the importance of both adjuvants and vaccination routes in the design and clinical translation of adjuvanted vaccines. Further research is needed to elucidate the mechanisms underlying the observed differences in efficacy and safety.
22
2025/12
Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) from sensory ganglia, often due to aging and other factors. Glycoprotein E (gE) is a vaccine antigen widely used to elicit specific humoral and cellular immune responses. Immediate-early protein 63 (IE63) is expressed during the latent phase, suggesting that it may serve as a potential antigen against HZ reactivation. In this study, researchers developed and evaluated the immunogenicity of HZ DNA vaccines encoding gE, IE63, IE63-2A-gE (where 2A is a self-cleaving sequence), or IE63-linker-gE in mice. The results demonstrated that each of these HZ DNA vaccines induced the production of VZV-specific antibodies. The neutralizing antibody titers elicited by IE63-2A-gE were comparable to those induced by gE or by a live attenuated HZ vaccine (LAV). The frequency of gE- or IE63-specific IFN-γ–producing T cells in intestinal lamina propria was also similar to that observed with LAV. Furthermore, compared with LAV, IE63-2A-gE, gE, and IE63 significantly enhanced the secretion of IFN-γ (in response to IE63) and IL-2 (in response to gE), indicating a Th1-biased immune response. In addition, IE63-2A-gE and gE elicited greater cytotoxic activity of CD8+ T cells than LAV. This study demonstrates that the IE63-2A-gE DNA vaccine can induce both humoral and cell-mediated immune responses, thereby providing a promising candidate for the development of a herpes zoster vaccine.