In response to the COVID-19 pandemic, different types of vaccines, such as inactive, live-attenuated, messenger RNA (mRNA), and protein subunit, have been developed against SARS-CoV-2. This has unintentionally created a unique scenario where heterologous prime-boost vaccination against a single virus has been administered to a large human population. Here, we aimed to analyze whether the immunization order of vaccine types influences the efficacy of heterologous prime-boost vaccination, especially mRNA and protein-based vaccines. We developed a new mRNA vaccine encoding the hemagglutinin (HA) glycoprotein of the influenza virus using the 3′-UTR and 5′-UTR of muscle cells (mRNA-HA) and tested its efficacy by heterologous immunization with an HA protein vaccine (protein-HA). The results demonstrated higher IgG2a levels and hemagglutination inhibition titers in the mRNA-HA priming/protein-HA boosting (R-P) regimen than those induced by reverse immunization (protein-HA priming/mRNA-HA boosting, P-R). After the viral challenge, the R-P group showed lower virus loads and less inflammation in the lungs than the P-R group did. Transcriptome analysis revealed that the heterologous prime-boost groups had differentially activated immune response pathways, according to the order of immunization. In summary, our results demonstrate that the sequence of vaccination is critical to direct desired immune responses. This study demonstrates the potential of a heterologous vaccination strategy using mRNA and protein vaccine platforms against viral infection.
17 October 2023 in Frontiers in Bioscience-Landmark
Several antiviral drugs are clinically approved to treat influenza that is a highly prevalent acute respiratory disease. However, emerging drug-resistant virus strains undermine treatment efficacy, highlighting the exigency for novel antiviral drugs to counter these drug-resistant strains. Plants and their derivates have been historically utilized as medicinal remedies, and extensive studies have evidenced the antiviral potential of phytochemicals. Notably, apigenin is a predominant flavonoid with minimal toxicity and substantial therapeutic effects in various disease models. Despite its many anti-inflammatory, anti-oxidant, anti-cancer, anti-bacterial, and other beneficial bioactivities, existing reviews have yet to focus on apigenin’s antiviral effects. Therefore, this review elucidates apigenin’s therapeutic and antiviral properties in vitro and in vivo, discussing its mode of action and future prospects. Apigenin’s remarkable inhibition by modulating multiple mechanisms against viruses has promising potential for novel plant-derived antiviral drugs and further clinical study developments.
Vaccines are one of the most powerful tools for preventing infectious diseases. To effectively fight pathogens, vaccines should induce potent and long-lasting immune responses that are specific to the pathogens. However, not all vaccines can induce effective immune responses, and the responses vary greatly among individuals and populations. Although several factors, such as age, host genetics, nutritional status, and region, affect the effectiveness of vaccines, increasing data have suggested that the gut microbiota is critically associated with vaccine-induced immune responses. In this review, I discuss how gut microbiota affects vaccine effectiveness based on the clinical and preclinical data, and summarize possible underlying mechanisms related to the adjuvant effects of microbiota. A better understanding of the link between vaccine-induced immune responses and the gut microbiota using high-throughput technology and sophisticated system vaccinology approaches could provide crucial insights for designing effective personalized preventive and therapeutic vaccination strategies.