Clinical and Experimental Vaccine Research最新文献

Tuberculosis (TB) is consistently ranked among the deadliest diseases worldwide, causing millions of deaths annually. Mycobacterium tuberculosis is the causative agent for this infection. Different antibiotics and vaccines have been discussed as potential treatments and prevention. Currently, there is only one licensed vaccine against TB, Bacillus Calmette-Guérin (BCG). Despite its protective efficacy against TB in children, BCG has failed to protect adults against pulmonary TB, lacks therapeutic value, and can cause complications in immunocompromised individuals. In this review, BCG, the most widely administered vaccine, is discussed, and the newest vaccines available in medicine are discussed. Based on the restrictions that prevent optimal BCG efficacy and the vaccines that are now being tested in various clinical studies, some criteria need to be considered in designing future vaccines.

Omicron variants present new challenges when it comes to understanding their impact on vaccines, antiviral strategies, and possible neurological consequences. This article describes the characteristics of the Omicron variant, its epidemiology, the efficacy of vaccines and monoclonal antibodies, and its association with lymphoid depletion. We also explore the neurological implications of Omicron, focusing on its association with encephalopathy and encephalitis. There are unique challenges associated with the Omicron variant, which is characterized by distinct mutations and increased transmissibility. For a better understanding of the effects of this disease and developing strategies to combat its spread, especially concerning neurological complications, ongoing research is necessary.

Purpose: In this study, an in-house enzyme-linked immunosorbent assay (ELISA) was developed and validated. The titer of ELISA was calculated using the reference line (RFL) method based on the standard curve drawn using the international reference anti-mouse serum NIBSC (National Institute for Biological Standards and Control) 97/642.

Materials and methods: In the development step, signal to noise was depicted to select the buffers that showed the most appropriate ratio. In the validation step, standard range, precision, dilution linearity, and specificity were confirmed, and RFL and parallel line (PLL) methods were compared in precision and dilution linearity.

Results: Coating concentration for plate was achieved at 0.1 µg/mL for pertussis toxin (PT), 0.15 µg/mL for filamentous hemagglutinin antigen (FHA), and 0.25 µg/mL for pertactin (PRN). The signal to noise ratio was 22.02 for PT, 14.93 for FHA, and 8.02 for PRN with 0.25% goat serum in phosphate-buffered saline (PBS) as a dilution buffer, and 2% skim milk in PBS as a blocking buffer. Based on the precision results, we assessed the lower limit of quantification by 1, 0.2, and 1.5 EU/mL concentration for PT, FHA, and PRN which met the ICH (International Council for Harmonization) M10 criteria of a 25% accuracy and total error of 40%. In specificity, homologous serum was spiked into heterologous serum and the accuracy met the criteria. There was no difference in the results between RFL and PLL calculations (p-value=0.3207 for PT, 0.7394 for FHA, 0.2109 for PRN).

Conclusion: ELISA validated with RFL calculation method in this study is a relatively accurate assay for mouse humoral immunogenicity test.

Purpose: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) usually causes a mild disease in children and the most serious consequence is multisystem inflammatory syndrome in children (MIS-C). Currently, there are no data about the protective role of vaccination performed by parents on children regarding the development of MIS-C. The aim of our study is to establish whether parental vaccination is related to MIS-C and the protective value of SARS-CoV-2 vaccination performed by parents against the occurrence of MIS-C in their children.

Materials and methods: Our retrospective single center study included 124 patients aged 1 month to 18 years admitted to emergency department from April 2020 to March 2022 for coronavirus disease 2019 disease.

Results: Parental vaccination was negatively correlated with the development of MIS-C: 4% of patients with both parents vaccinated developed MIS-C, while patients with no parent vaccinated to have developed MIS-C were 20%.

Conclusion: Parental vaccination could be an important factor influencing the course of the disease and reduces the probability that a child would develop MIS-C by 83% if both parents vaccinated.

There have been many studies on the adverse effects of coronavirus disease 2019 (COVID-19) vaccines but the urinary incontinence after COVID-19 vaccination is rare. Here, we report an 8-year-old boy presented to outpatient department, Thai Binh University of Medicine Hospital, Thai Binh, Vietnam with complaints of urinary incontinence for the past 2 weeks, following the first dose of the messenger RNA vaccine. He had no other abnormalities in clinical and laboratory exams. This clinical situation suggested vaccine side effects. No specific treatment was administered upon diagnosis without toilet and bladder training. Subsequent monitoring revealed a gradual reduction in symptoms over 2 months, with complete recovery achieved at the 14th week from the onset of symptoms, without necessitating any medical intervention. This case highlights the need for thorough evaluation and assessment of potential adverse effects following vaccination, including uncommon presentations.

Purpose: The immunogenicity of vaccines containing the canine adenovirus (CAdV) type 2 (CAdV-2) variant has not yet been reported. We prepared a novel inactivated CAdV-2 variant vaccine using the CAV2232-41 strain, and evaluated its safety and immunogenicity in raccoon dogs.

Materials and methods: The growth kinetics of CAV2232-41 were determined using Madin-Darby Canine Kidney (MDCK) cells. The nucleotide sequences of CAV2232 and CAV2232-41 were determined by next-generation sequencing. To generate the CAdV-2 variant vaccine, CAV2232-41 propagated in the MDCK cells was inactivated with 0.1% formaldehyde. Two vaccines were prepared by blending inactivated CAV2232-41 with Cabopol and Rehydragel adjuvants. Safety and immunogenicity of the CAV2232C and CAV2232R vaccines were evaluated in guinea pigs. Safety and immunogenicity of the CAV2232C vaccine were also evaluated in raccoon dogs. The virus neutralizing antibody (VNA) titer against CAV2232-41 was measured in sera collected from immunized guinea pigs and raccoon dogs.

Results: CAV2232-41 showed the highest viral titer on days 4-6 post-inoculation and had a deletion in the E3 gene, which was confirmed as a CAdV-2 variant. Guinea pigs inoculated with CAV2232C showed slightly higher VNA titers than those inoculated with CAV2232R 2 weeks after booster vaccination. Raccoon dogs immunized with the CAV2232C vaccine developed high mean VNA titers, while non-vaccinated raccoon dogs were antibody-negative.

Conclusion: The CAV2232C vaccine is safe and induces a protective VNA titer in raccoon dogs.

Structural vaccinology is pivotal in expediting vaccine design through high-throughput screening of immunogenic antigens. Leveraging the structural and functional characteristics of antigens and immune cell receptors, this approach employs protein structural comparison to identify conserved patterns in key pathogenic components. Molecular modeling techniques, including homology modeling and molecular docking, analyze specific three-dimensional (3D) structures and protein interactions and offer valuable insights into the 3D interactions and binding affinity between vaccine candidates and target proteins. In this review, we delve into the utilization of various immunoinformatics and molecular modeling tools to streamline the development of broad-protective vaccines against coronavirus disease 2019 variants. Structural vaccinology significantly enhances our understanding of molecular interactions between hosts and pathogens. By accelerating the pace of developing effective and targeted vaccines, particularly against the rapidly mutating severe acute respiratory syndrome coronavirus 2 and other prevalent infectious diseases, this approach stands at the forefront of advancing immunization strategies. The combination of computational techniques and structural insights not only facilitates the identification of potential vaccine candidates but also contributes to the rational design of vaccines, fostering a more efficient and targeted approach to combatting infectious diseases.

Purpose: Brucellosis, a zoonotic infectious disease, is a worldwide health issue affecting animals and humans. No effective human vaccine and the complications caused by the use of animal vaccines are among the factors that have prevented the eradication of the disease worldwide. However, bio-engineering technologies have paved the way for designing new targeted and highly efficacious vaccines. In this regard, the study aimed to evaluate immunity induced by mannosylated niosome containing Brucella recombinant trigger factor/Bp26/Omp31 (rTBO) chimeric protein in a mouse model.

Materials and methods: rTBO as chimeric antigen (Ag) was expressed in Escherichia coli BL21 (DE3) and, after purification, loaded on niosome and mannosylated niosome. The characteristics of the nanoparticles were assessed. The mice were immunized using rTBO, niosome, and mannosylated niosome-rTBO in intranasal and intraperitoneal routes. Serum antibodies (immunoglobulin [Ig]A, IgG, IgG1, and IgG2a) and splenocyte cytokines (interferon-gamma, interleukin [IL]-4, and IL-12) were evaluated in immunized mice. Finally, immunized mice were challenged by B. melitensis and B. abortus. A high antibody level was produced by niosomal antigen (Nio-Ag) and mannosylated noisomal antigen (Nio-Man-Ag) compared to the control after 10, 24, and 38 days of immunization. The IgG2a/IgG1 titer ratio for Nio-Man-Ag was 1.2 and 1.1 in intraperitoneal and intranasal methods and lower than one in free Ag and Nio-Ag. Cytokine production was significantly higher in the immunized animal with Ag-loaded nanoparticles than in the negative control group (p<0.05). Moreover, cytokine and antibody levels were significantly higher in the injection than in the inhalation method (p<0.05).

Results: The combination of mannosylated noisome and rTBO chimeric proteins stimulate the cellular and humoral immune response and produce cytokines, playing a role in developing the protective acquired immune response in the Brucella infectious model. Also, the intraperitoneal route resulted in a successful enhancement of cytokines production more than intranasal administration.

Conclusion: Designing an effective vaccine candidate against Brucella that selectively induces cellular and humoral immune response can be done by selecting a suitable nanoniosome formulation as an immunoadjuvant and recombinant protein as an immune response-stimulating Ag.

Purpose: Sleeping disorders were reported in many patients who took vaccines during previous pandemics. We aim to investigate the relationship between coronavirus disease 2019 (COVID-19) vaccines and the incidence of narcolepsy symptoms in the Jordanian population.

Materials and methods: We used a descriptive, cross-sectional, online self-administered survey conducted between December 2022 and May 2023. The survey targeted males and females above the age of 18 years who took any type of COVID-19 vaccine, had no chronic diseases, and had no sleep disorders prior to taking the vaccine. The survey was distributed via social media platforms.

Results: A total of 873 participants were included in this study, consisting of 44.4% males and 55.6% females, with the majority being in the 18-29 age group. Most participants (79.8%) received two vaccine doses, with the Pfizer vaccine being the most common. Nearly half of the participants reported excessive daytime sleepiness. Sleep paralysis and hypnagogic hallucinations were reported by a notable proportion of participants, but no significant differences were found among the vaccine types. Sleep attacks and fragmented nighttime sleep were associated with the number of vaccine doses received, suggesting a possible influence of the dose count on these symptoms. The presence of excessive daytime sleepiness, sudden loss of muscle tone, sleep paralysis, and hypnagogic hallucinations showed no significant association with the number of doses taken.

Conclusion: We hypothesize a possible link between COVID-19 vaccination and the emergence of narcolepsy symptoms in Jordanian individuals. Additional investigations and continuous monitoring to determine the extent of the risk and uncover potential mechanisms behind this connection should be performed.

Purpose: Enterovirus 71, a pathogen that causes hand-foot and mouth disease (HFMD) is currently regarded as an increasing neurotropic virus in Asia and can cause severe complications in pediatric patients with blister-like sores or rashes on the hand, feet, and mouth. Notwithstanding the significant burden of the disease, no authorized vaccine is available. Previously identified attenuated and inactivated vaccines are worthless over time owing to changes in the viral genome.

Materials and methods: A novel vaccine construct using B-cell derived T-cell epitopes from the virulent polyprotein found the induction of possible immune response. In order to boost the immune system, a beta-defensin 1 preproprotein adjuvant with EAAAK linker was added at the N-terminal end of the vaccine sequence.

Results: The immunogenicity of the designed, refined, and verified prospective three-dimensional-structure of the multi-epitope vaccine was found to be quite high, exhibiting non-allergenic and antigenic properties. The vaccine candidates bound to toll-like receptor 3 in a molecular docking analysis, and the efficacy of the potential vaccine to generate a strong immune response was assessed through in silico immunological simulation.

Conclusion: Computational analysis has shown that the proposed multi-epitope vaccine is possibly safe for use in humans and can elicit an immune response.