Clinical and Experimental Vaccine Research最新文献

Vaccination is a cornerstone of public health, saving millions of lives each year by preventing a variety of infectious diseases. Yet, despite global vaccination efforts, emerging research highlights significant geographical disparities in vaccine efficacy and immunogenicity. These variations underscore the critical interplay between immunological factors and environmental, genetic, and nutritional elements across different populations. Our review article aimed to explore the multifactorial reasons behind geographical variations in vaccine efficacy. Also, this study has shown how important host factors like age, obesity, gender, and genetic diversity, especially within the major histocompatibility complex, are in determining how well a vaccine works. Nutritional status, namely deficiencies in micronutrients such as vitamins and zinc, and lifestyle factors including stress, sleep, alcohol consumption, and physical activity are also shown to have profound effects on vaccine-induced immunity. Importantly, our paper also brought to light the influence of microbial and ecological factors, such as the gut microbiome and environmental pollutants, on the immune system's response to vaccination. The findings emphasize the importance of tailoring vaccination strategies to accommodate the unique immunological landscapes shaped by geographical and societal factors. This tailored approach could enhance vaccine efficacy, reduce disparities in vaccine response, and ultimately contribute to the global fight against infectious diseases.

Purpose: Staphylococcus aureus is a Gram-positive bacterium that most frequently acquires antibiotic resistance. As an opportunistic pathogen, it can cause conditions such as bacteremia, sepsis, and myocarditis. Due to the social need for a vaccine against methicillin-resistant Staphylococcus aureus (MRSA), many research groups have been designing and studying vaccines for decades. In this study, we developed a multivalent vaccine and evaluated its efficacy by applying a novel adjuvant, β-glucan.

Materials and methods: A vaccine composed of four pore-forming toxins from S. aureus was administered to rabbits 3 times, after which they were challenged with S. aureus USA 300 LAC strain. We measured changes in the rabbits' body weight to monitor systemic adverse reactions and analyzed the total immunoglobulin G antibody titer against the four antigens using enzyme-linked immunosorbent assay. For each rabbit, the number of abscesses and colony-forming units (CFU) in the kidneys were measured.

Results: In all vaccinated groups, strong antibody responses against the four antigens were observed. After challenging with MRSA, the vaccinated groups showed less weight change compared to the non-vaccinated groups (average 5.7% versus 13.5%). Additionally, the number of renal abscesses was significantly lower in the vaccinated groups, with three individuals in group 1 (four antigens adjuvanted with β-glucan_PK1) showing no abscess formation. The number of bacteria identified in the kidneys was also statistically significantly lower in the vaccinated group compared to the non-vaccinated group.

Conclusion: We demonstrated that the four toxoid antigens we selected can protect against S. aureus infection in a rabbit model and that β-glucan could be used as an immune enhancer. Overall, our study shows that new antigen combinations can induce protective immunity in animal models and that a toxin-based vaccine can help control bacterial colonization.

Vaccination provides great protection against several infections, including coronavirus disease 2019 (COVID-19). However, the endeavor faces multiple context-specific problems that affect its uptake, leading to vaccine hesitancy. Vaccine hesitancy is a focal barrier to the success of COVID-19 vaccination programs. This umbrella review aimed to present a summary of global data regarding vaccine hesitancy and acceptance rates among medical students, health professionals, and health care workers. In this regard, two databases, PubMed and Scopus, were selected for data retrieval and analysis. A search term and an inclusion/exclusion criterion were applied to summarize the findings of existing systematic reviews. A pooled prevalence of vaccine acceptance and hesitancy with 95% confidence interval (CI) was taken as a prerequisite for this review. The results found a high percentage of COVID-19 vaccination ranging from 13.1% (95% CI, 6.9%-20.9%) to 46% (95% CI, 0.38%-0.54%), while the percentage of acceptance varied from 46% (95% CI, 37%-54%) to 83.0% (95% CI, 71%-96%) among medical students, health professionals, and health care workers. This umbrella review found a high percentage of COVID-19 vaccine hesitancy among medical students, health professionals, and health care workers. Further studies analyzing the determinants of vaccine hesitancy are important predictors for successful vaccination programs at the global level.

Purpose: This phase I study aimed to assess the safety, tolerability, and immunogenicity of the PIKA-adjuvanted recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein subunit vaccine in healthy adults aged 18 years and older.

Materials and methods: This is a phase I, open-label, dose-escalation study at three dose levels (5 µg, 10 µg, and 20 µg) of the PIKA coronavirus disease 2019 (COVID-19) vaccine administered intramuscularly. The three vaccine arms are (A) subjects who have never received any COVID-19 vaccination or have had COVID-19 infection for >6 months prior to enrolment; (B1) subjects whose COVID-19 primary vaccination series was completed with an inactivated COVID-19 vaccine; and (B2) subjects whose primary series was completed with messenger RNA COVID-19 vaccine.

Results: Subjects who reported solicited adverse events (AEs) within seven days post-vaccination ranged from 35% to 60% within each vaccine arm. Most solicited AEs were mild local pain and tenderness. Systemic solicited AEs were only reported in Arm A. In all three vaccine arms, neutralizing antibody geometric mean titers were highest at day 28 (Arms B1 and B2) or day 35 (Arm A) than at baseline for all dose levels against the Wuhan (wild original SARS-CoV-2 virus, Wuhan-Hu-1), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. These were sustained at day 183. Seroconversion rates at day 35 (Arm A, 85.7%-92.9%) or day 183 (Arms B1, 90.9%-100.0%, and B2, 18.2%-36.4%) and geometric mean fold rises were highest in the 5-µg dose level against all three variants.

Conclusion: The PIKA-adjuvanted recombinant SARS-CoV-2 S protein subunit vaccine showed promising immunogenicity profile with no safety concerns. A dose-dependent immune response was observed, with slight advantages seen in low-dose (5 µg and 10 µg) groups (ClinicalTrials.gov registration number: NCT05305300).

The present study aimed to evaluate the key characteristics of Toxoplasma gondii rhoptry protein 4 (TgROP4), including physicochemical parameters, structural features, immunogenic epitopes, and virtual immune simulation, using several bioinformatics-based servers and tools. Based on allergenicity and antigenicity outputs, the TgROP4 protein seemed to have an immunogenic and non-allergenic nature. The quality of the three-dimensional (3D) structure improved after refinement, according to the outcomes of the Ramachandran plot and the ProSA-web servers. ABCpred and SVMTriP web tools were used to predict linear B lymphocyte epitopes and found several promising epitopes. Acceptable antigenicity, hydrophilicity, beta-turn, Bepipred linear epitope 2.0, flexibility, and surface accessibility scores were obtained through the Immune Epitope Database (IEDB). Also, seven discontinuous B-cell epitopes ranging from scores 0.966 to 0.848 were found in the 3D model of TgROP4 via the ElliPro. The IEDB findings showed T-cell epitopes on TgROP4 protein are capable to strongly bind to the major histocompatibility complex classes. In silico immune simulation was performed using C-ImmSim server and showed three injections of TgROP4 protein at 4-week intervals is capable to elicit adequate humoral and cell-mediated immune responses.

Purpose: We aim to analyze the proportion and level of coronavirus disease 2019 (COVID-19) seropositivity in patients with systemic lupus erythematosus (SLE) and explore factors associated with lower anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (S-RBD) antibody levels.

Materials and methods: A cross-sectional study involving patients with SLE was conducted. We included those aged 18-60 years, either unvaccinated or had received inactivated vaccine (CoronaVac; Sinovac Biotech Ltd., China). Furthermore, participants were tested for anti-SARS-CoV-2 S-RBD antibody levels and SARS-CoV-2 surrogate virus neutralization test, and comparative test analysis was employed.

Results: This study included 159 subjects of whom 92 and 67 were SLE subjects and controls, respectively. Significantly higher seropositive results were noted in patients with SLE receiving vaccine (96.9% versus 3.1%). Unvaccinated SLE patients receiving cyclophosphamide (CYC) had higher anti-RBD levels compared to unvaccinated SLE patients not receiving CYC (23.81 [interquartile range (IQR), 2.26-78.85] versus 2.13 [IQR, 0.1-12.5]), whereas vaccinated SLE patients receiving CYC had lower anti-RBD levels compared to vaccinated SLE patients not receiving CYC (15.5 [IQR, 6.62-35.09] and 69.77 [IQR, 17.48-201]). In the vaccinated SLE group, a lower value of anti-SARS-CoV-2 RBD antibody levels was observed in patients receiving mycophenolate mofetil and those with chronic kidney disease. No correlation was noted between disease activity and organ involvement with lower antibody response.

Conclusion: The increase in COVID-19 antibody levels in patients with SLE may be affected by exposure to hospital settings and vaccine. Furthermore, CYC treatment is associated with lower antibody response after receiving vaccine.

Purpose: This study evaluated the safety and immunogenicity of the PIKA-adjuvanted recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein subunit vaccine as a booster dose for healthy adults who had previously received two or more doses of an inactivated coronavirus disease 2019 (COVID-19) vaccine.

Materials and methods: The study was a phase II multicenter, double-blinded, comparator-controlled, randomized trial. Participants were randomly assigned to receive either the PIKA COVID-19 vaccine booster dose or an inactivated COVID-19 vaccine (Sinovac, China). Safety was assessed based on adverse events, while immunogenicity was measured by neutralizing antibodies against SARS-CoV-2 and serum immunoglobulin G (IgG) levels. Data on safety and immunogenicity were collected in the short-term (within 14 days after the booster dose) and long-term (from 90 to 365 days after the booster dose).

Results: The PIKA-adjuvanted vaccine demonstrated a significant increase in neutralizing antibodies against the Omicron variant (geometric mean ratio [GMR]=2.0 on day 7, p-value <0.001; GMR=2.7 on day 14, p-value <0.001) and the wild type SARS-CoV-2 virus (GMR=2.3 on day 7, p-value <0.001; GMR=2.8 on day 14, p-value<0.001) in the early post-vaccination period when compared to the inactivated vaccine. Additionally, the PIKA COVID-19 vaccine showed higher seroconversion rates for neutralizing antibodies against both variants during the first 14 days post-vaccination. However, there were no significant differences in neutralizing antibody levels between the two vaccines from day 90 to day 360 post-vaccination. Serum IgG antibody levels for the PIKA COVID-19 vaccine were also higher throughout the study period. The incidence of adverse events was slightly higher in the PIKA COVID-19 group, with the most common events being pain at the injection site and headache. All adverse events were mild or moderate, with no reports of severe or life-threatening adverse events in either group.

Conclusion: The PIKA COVID-19 vaccine, when administered as a booster dose, showed promising short- and long-term immunogenicity with no emergent safety issues identified. The booster dose of the PIKA COVID-19 vaccine elicited a robust immune response against various SARS-CoV-2 variants and provided some seroprotection for up to 360 days (ClinicalTrials.gov registration number: NCT05463419).

Purpose: The effects of coronavirus disease 2019 vaccination on fertility and pregnancy have turned out to be a main topic of public attention. Inactivated or recombinant protein vaccines are a reliable and safe method but mostly suffer from weak immunogenicity just in case formulated with a suitable adjuvant. The purpose of this research was to assess the impacts of new SpikoGen subunit vaccine administration during pregnancy on organogenesis in the rat fetus, which is a novel achievement in teratogenesis studies.

Materials and methods: In the first group (G1) animals received normal saline. A dose of 25 µg of the vaccine was administered to groups of rats as follows: groups 2, 3, 4, and 5 received two doses of vaccine on different days before and after start of pregnancy. On day 21, after the caesarean process, the effects of the vaccine were estimated by morphological, skeletal, and histological studies.

Results: Administration of the SpikoGen vaccine had no significant effect on weight, head diameter, tail length, and length of the fetuses to their tail. There were no malformations, toes and legs were fully developed, and all internal organs of the fetus were completely formed. Also, there was no difference in the overall skeletal opacity and density between the control and treatment groups.

Conclusion: The results of this study indicated no negative impacts of the vaccine administration during pregnancy on developing of fetuses in rats.

Purpose: A booster coronavirus disease 2019 (COVID-19) vaccination was proposed to preserve immunity and prevent new variants of the severe acute respiratory syndrome coronavirus 2 virus. The objectives of this study are to investigate clinical manifestations, associated factors and course of cutaneous reactions after the booster dose of COVID-19 vaccination, compared to the recommended 1st and 2nd doses.

Materials and methods: This retrospective cohort study was conducted at Siriraj Hospital, Bangkok. Adult patients who reported cutaneous reactions after COVID-19 vaccination from April 2021 to February 2022 were included. Data were collected from electronic medical records and analyzed.

Results: A total of 521 subjects with a median age of 38 years were included. Females predominated (80.2%). Most reactions were reported after receiving CoronaVac (49.1%) and ChAdOx1 nCoV-19 (46.3%). The injection site reaction was the most reported. Twenty-one patients reported rash after the 3rd booster dose, with messenger RNA vaccines in most cases. Patients in this group had significantly fewer injection site reactions compared to those with the 1st and 2nd vaccination (70.6% vs. 91.5%) with an increasing proportion of new-onset urticaria (17.6% vs. 5.4%, p=0.023). The rash after the 3rd booster vaccination tended to have a longer duration of reactions (p=0.001). Boosting with a vaccine different from the 1st dose may not affect the reaction. Age and sex did not affect booster rash. In this study, no serious cutaneous reactions were found.

Conclusion: Most adverse cutaneous reactions after COVID-19 vaccination are mild in severity, especially after booster vaccination, and should not discourage the benefits of getting vaccinated.