TNFepitope: A webserver for the prediction of TNF-α inducing epitopes

Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV infection in China in 2003, Chinese scientists have made lots of efforts to prevent and control this disease, including developing diagnosis methods, vaccines and antiviral agents against HMPV, as well as conducting epidemiological investigations. However, effective vaccines or special antiviral agents against HMPV are currently not approved, thus developing early diagnosis methods and knowing its epidemiological characteristics will be beneficial for HMPV control. Here, we summarized current research focused on the epidemiological characteristics of HMPV in China and its available detection methods, which will be beneficial to increase the public awareness and disease control in the future. 

Epidemiology and diagnosis technologies of human metapneumovirus in China: a mini review

INTRODUCTION
The mRNA vaccine technologies have progressed rapidly in recent years. The COVID-19 pandemic has accelerated the application of mRNA vaccines, with research and development and clinical trials underway for many vaccines. Application of the quality by design (QbD) framework to mRNA vaccine development and establishing standardized quality control protocols for mRNA vaccines are essential for the continued development of high-quality mRNA vaccines.


AREAS COVERED
mRNA vaccines include linear mRNA, self-amplifying mRNA, and circular RNA vaccines. This article summarizes the progress of research on quality control of these three types of vaccines and presents associated challenges and considerations.


EXPERT OPINION
Although there has been rapid progress in research on linear mRNA vaccines, their degradation patterns remain unclear. In addition, standardized assays for key impurities, such as residual dsRNA and T7 RNA polymerase, are still lacking. For self-amplifying mRNA vaccines, a key focus should be control of stability in vivo and in vitro. For circular RNA vaccines, standardized assays, and reference standards for determining degree of circularization should be established and optimized.

Research progress on the quality control of mRNA vaccines.

With the development of novel vaccine strategies, T-cell epitope-based vaccines have become promising prophylactic and therapeutic tools against infectious diseases that cannot be controlled via traditional vaccines. T-cell epitope-based vaccines leverage specific immunogenic peptides to elicit protective T-cell responses against infectious pathogens. Compared to traditional vaccines, they provide superior efficacy and safety, minimizing the risk of adverse side effects. In this review, we summarized and compared the prediction and identification methods of T-cell epitopes. By integrating bioinformatic prediction and experimental validation, efficient and precise screening of T-cell epitopes can be achieved. Importantly, we delved into the development approaches to diverse T-cell epitope-based vaccines, comparing their merits and demerits, as well as discussing the prevalent challenges and perspectives in their applications. This review offers fresh perspectives for the formulation of safe and efficacious epitope-based vaccines for the devastating diseases against which no vaccines are currently available. 

T-Cell Epitope-Based Vaccines: A Promising Strategy for Prevention of Infectious Diseases

A vaccine is a biological preparation that contains the antigen capable of stimulating the immune system to form the defense against pathogens. Vaccine development often confronts big challenges, including time/energy-consuming, low efficacy, lag to pathogen emergence and mutation, and even safety concern. However, these seem now mostly conquerable through constructing the advanced translational platforms that can make innovative vaccines, sometimes, potentiated with a distinct multifunctional VADS (vaccine adjuvant delivery system), as evidenced by the development of various vaccines against the covid-19 pandemic at warp speed. Particularly, several covid-19 vaccines, such as the viral-vectored vaccines, mRNA vaccines and DNA vaccines, regarded as the innovative ones that are rapidly made via the high technology-based translational platforms. These products have manifested powerful efficacy while showing no unacceptable safety profile in clinics, allowing them to be approved for massive vaccination at also warp speed. Now, the proprietary translational platforms integrated with the state-of-the-art biotechnologies, and even the artificial intelligence (AI), represent an efficient mode for rapid making innovative clinical vaccines against infections, thus increasingly attracting interests of vaccine research and development. Herein, the advanced translational platforms for making innovative vaccines, together with their design principles and immunostimulatory efficacies, are comprehensively elaborated.

Innovative translational platforms for rapid developing clinical vaccines against COVID-19 and other infectious disease.

Human metapneumovirus (HMPV) is one of the main pathogens causing severe respiratory infections in children, as a common cause of immunodeficiency-related deaths in children and elderly individuals, the prevalence of HMPV has been showing an increasing trend during the last years. However, no vaccines or effective treatment plans are available currently. In this present, based on candidate proteins highly associated with viral virulence and has promising protective potential, we screened for immunodominant cytotoxic T cells, helper T cells, and Linear B-cell epitopes from the most promising candidate Fusion protein, together with G, SH, M, and M2. All epitopes were predicted to have strong antigenicity by Vaxijen and pose no potential toxicity, allergenicity, or hormonology to human proteins by Toxinpred, Allerpred, and Blast analysis, meanwhile, high conservancy is demanded to cover different subtypes. adjuvants β-defensin II and Pam2Cys was attached with EAAAK linkers to improve vaccine's efficiency. Then, calculation of physicochemical properties proved the protein vaccine as a product can stably exist in the human body. Besides, we assessed the docking between the vaccine and immune receptors to evaluate its ability to stimulate immune responses, and the dynamic simulation further confirmed that the vaccine can tightly bind with immune receptors, which approved that the construction has the potential to induce strong humoral and cellular immune response. Finally, the vaccine was constructed into a multi-epitope mRNA vaccine, the immune simulations suggest that this is a vaccine candidate for controlling HMPV infection.

Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus.

Staphylococcus aureus is an extraordinarily versatile pathogen, which is currently the most common cause of nosocomial and community infections. Considering that increased antibiotic resistance may hasten the spread of S. aureus, developing an effective vaccine can possibly aid in its control. The RNA vaccine coding immunodominance epitopes from bacteria provide a potential method to induce T and B cell immune responses by translating them into cells. Furthermore, using bioinformatics to create circular RNA vaccines can ensure that the translation of the vaccine is potent and durable. In this study, 7 cytotoxic T lymphocyte (CTL) epitopes, 4 helper T lymphocyte (HTL) epitopes, and 15 B cell epitopes from 6 proteins that are closely associated with the S. aureus virulence and invasion and critical to natural immune responses were mapped. To verify their interactions, all epitopes were docked with the corresponding MHC alleles. The final vaccine was composed of 26 epitopes and the adjuvant β-defencin, and a disulfide bond was also introduced to improve its stability. After the prediction of structure and characteristics, the developed vaccine was docked with TLR2 and TLR4, which induce immunological responses in S. aureus infection. According to the molecular dynamic simulation, the vaccine might interact strongly with TLRs. Meanwhile, it performed well in immunological simulation and population coverage prediction. Finally, the vaccine was converted into a circular RNA using a series of helper sequences to aid in vaccine circulation translation. Hopefully, this proposed structure will be proven to serve a viable vaccine against S. aureus.Communicated by Ramaswamy H. Sarma.

Development of a novel circular mRNA vaccine of six protein combinations against Staphylococcus aureus.

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Development of a novel multi-epitope mRNA vaccine candidate to combat HMPV virus.

Development of a novel circular mRNA vaccine of six protein combinations against Staphylococcus aureus.