VLPs were encapsulated by ZIF-8 to improve the thermal stability. VLPs-ZIF-8 promotes the cellular uptake of VLPs and assists VLPs in escaping from lysosomes. VLPs-ZIF-8 vaccine showed better heat resistance, cellular and humoral immune responses.

Ran X, et al. J Vet Sci. 2023 May;24:e48. https://doi.org/10.4142/jvs.22307

Coronaviruses in general are a zoonotic pathogen with significant cross-species transmission. They are widely distributed in nature and have recently become a major threat to global public health. Vaccines are the preferred strategy for the prevention of coronaviruses. However, the rapid rate of virus mutation, large number of prevalent strains, and lag in vaccine development contribute to the continuing frequent occurrence of coronavirus diseases. There is an urgent need for new antiviral strategies to address coronavirus infections effectively. Antiviral drugs are important in the prevention and control of viral diseases. Members of the genus coronavirus are highly similar in life-cycle processes such as viral invasion and replication. These, together with the high degree of similarity in the protein sequences and structures of viruses in the same genus, provide common targets for antiviral drug screening of coronaviruses and have led to important advances in recent years. In this review, we summarize the pathogenic mechanisms of coronavirus, common drugs targeting coronavirus entry into host cells, and common drug targets against coronaviruses based on biosynthesis and on viral assembly and release. We also describe the common targets of antiviral drugs against coronaviruses and the progress of antiviral drug research. Our aim is to provide a theoretical basis for the development of antiviral drugs and to accelerate the development and utilization of commonly used antiviral drugs in China.

Mucosal immunization represents a promising strategy for preventing enteric infections. Rotavirus (RV), a leading gastrointestinal pathogen distinguished by its remarkable stability and segmented double-stranded RNA genome, has been engineered into a versatile oral vaccine vector through advanced reverse genetics systems. The clinical efficacy of live-attenuated RV vaccines highlights their unique capacity to concurrently induce mucosal IgA responses and systemic neutralizing antibodies, positioning them as a multiple action vector for multiple immune protection. In this review, we summarize the RV colonization of the intestine and stimulation of intestinal immunity, as well as recent advancements in RV reverse genetics, and focus on their application in the rational design of a multivalent mucosal vaccine vector targeting enteric pathogens considering the advantages and challenges of RV as a vector. We further propose molecular strategies to overcome genetic instability in recombinant RV vectors, including the codon optimization of heterologous inserts. These insights provide a theoretical foundation for developing next-generation mucosal immunization platforms with enhanced safety, stability, and cross-protective efficacy.

The segmented genome of live-attenuated rotavirus (RV) vaccines provides an ideal platform for developing multivalent vaccines against enteric pathogens. Here, we engineered the commercial human RV vaccine strain LLR as a vector to deliver Clostridium perfringens alpha-toxin (CPA), a critical virulence factor associated with gastroenteritis. A screen of four 2A peptide sequences identified that porcine teschovirus-1 2A (P2A) preceded by an N-terminal GSG spacer enabled optimal cleavage and antigen expression. In mice, the resulting recombinant virus elicited potent systemic antibody responses against both RV and CPA following oral administration. When tested in a maternal immunization model, intramuscular immunization of cows generated high titers of neutralizing antibodies in colostrum, demonstrating its potential utility for passive immunization. By integrating a key bacterial antigen into a licensed RV vaccine backbone, we establish a versatile strategy to combat viral-bacterial co-infections and polymicrobial enteric diseases, offering a promising new approach to reduce the global burden of diarrheal mortality. IMPORTANCE: The lack of vaccines targeting polymicrobial enteric infections represents a critical gap in the fight against diarrheal diseases, a leading cause of infant mortality worldwide. To bridge this gap, we engineered a novel bivalent vaccine designed to provide dual protection against rotavirus and Clostridium perfringens alpha-toxin (CPA)-mediated disease. Leveraging an enhanced reverse genetics system, we successfully utilized the commercialized rotavirus vaccine strain LLR as a viral vector to express the key C. perfringens virulence factor, CPA. This strategy not only offers a path to broader protection against diarrheal disease but also establishes a versatile platform for developing vaccines against other viral-bacterial co-infections.