Clinical and Experimental Vaccine Research最新文献

Purpose: The development of a universal avian influenza vaccine remains a critical issue for both the global public health and poultry industries. The hemagglutinin (H) stem/stalk region of highly pathogenic avian influenza viruses (HPAIVs) is capable of inducing broadly neutralizing antibodies but is limited by its poor immunogenicity.

Materials and methods: To increase the immunogenicity of the stem domain, we engineered a recombinant fusion construct consisting of the stem domain of the H5 subtype and the nontoxic cholera toxin B subunit (CTB), a well-characterized mucosal adjuvant and immunomodulator. C57BL/6 mice were immunized intraperitoneally with the CTB-H5 stem fusion protein. Humoral immune responses and virus-neutralizing activities were subsequently assessed.

Results: Mice immunized with CTB-H5 stem fusion protein developed significantly higher serum immunoglobulin G titers and increased binding affinity to the native trimeric H5 antigen. Sera from the CTB-H5 stem group demonstrated enhanced virus-neutralizing activity in plaque reduction assays against the H5N2 virus. These results suggest that CTB fusion significantly enhances the immunogenicity and protective potential of the conserved H5 stem domain against the H5N2 virus.

Conclusion: These findings support the use of CTB as an effective adjuvant platform for the development of stem-based influenza vaccines targeting HPAIVs.

Purpose: To present, to the best of our knowledge, the largest African case series of autoimmune manifestations (AIM) after coronavirus disease 2019 (COVID-19) vaccination.

Materials and methods: Cases were collected consecutively from March 2021 to December 2022 from the various departments of the university teaching hospital of Monastir. Autoimmunity biomarkers were investigated mainly in the laboratory of immunology of the same hospital. Anti-nuclear antibody (ANA) screening was performed by indirect immunofluorescence on HEp-2 cells (Euroimmun) with a positivity titer ≥1/180. Typing was done by enzyme-linked immunosorbent assay (ELISA; Biosystems) or line-blot (Euroimmun). The assessment of the other autoantibodies was performed with various techniques (indirect immunofluorescence, ELISA, line- blot).

Results: This case series reports 14 patients (age range, 34-69 years; sex ratio, 1:1) who developed AIM after COVID-19 vaccination with the Pfizer BioNTech, Oxford-AstraZeneca, Johnson & Johnson's Janssen, or Sputnik V vaccines between March 2021 and December 2022. The clinical onset occurred 1 week to 2 months after the last administrated dose. Immunological evaluation revealed positive ANA in 13 cases (titer 1/180 to 1/3,200). Autoantibodies typing revealed anti-mitochondria type 2 in 4 cases, anti-SSA in 3 cases, and anti-DFS70 in 2 cases. Nine patients received specific treatments for diagnosed autoimmune diseases (AID), whereas the others showed non-specific immune stimulation, reactive arthritis, myositis, and cerebral venous thrombosis, which improved with symptomatic treatment.

Conclusion: This series suggests a link between severe acute respiratory syndrome coronavirus 2 vaccination and triggered or revealed AID or AIM.

Purpose: Enhancing vaccine coverage among children is crucial to preventing the long-term consequences of dengue fever (DF) infections. This study aims to identify sociodemographic factors influencing parents' willingness to pay (WTP) for future dengue vaccine products in Southeast Sulawesi.

Materials and methods: An observational study design with a multicentred cross-sectional approach was employed, involving 510 parents participating in integrated health service activities (Posyandu) across 5 regencies/cities in Southeast Sulawesi. Data were collected using a modified questionnaire from previous studies, covering sociodemographic factors and WTP for the dengue vaccine. The questionnaire first asked about willingness to pay, followed by reasons if respondents were unwilling. Conversely, for respondents willing to pay, the contingent valuation method was applied, utilizing direct inquiries about the amount they were willing to pay. This involved a bidding technique followed by an open-ended question to determine the exact value respondents were willing to pay for the vaccine. The data were processed and analysed using IBM SPSS version 26. To identify the factors influencing WTP for the vaccine, a χ² test was conducted using IBM SPSS version 26.

Results: The average WTP among parents was IDR 134,686 (USD 8.27), which decreased to IDR 108,108 (USD 6.64) when government subsidies were considered. Five factors significantly influenced the WTP for the vaccine: sex, education level, monthly income, previous experience with the disease, and prior knowledge of the dengue vaccine.

Conclusion: The government and related health institutions need to improve public awareness and knowledge about DF and dengue vaccination.

Purpose: Differentiated airway epithelial cell cultures closely mimic the in vivo airways. We compared the structure and cytokine response of well-differentiated human nasal epithelial (HNE) cells obtained from healthy infants (iHNE) and adults (aHNE).

Materials and methods: Human bronchial epithelial (HBE) progenitor (n=4) and primary HNE cells (n=4 aHNE; n=10 iHNE) were cultured using a modification of the air-liquid interface (ALI) approach. For differentiated HBE and HNE cell cultures, representative transwells were fixed and then stained for ciliated and goblet cells. Low (400 pfu) and high (10⁵ pfu) inoculums of recombinant green fluorescent protein-expressing respiratory syncytial virus (RSV) were added apically to the ALI cultures. The concentrations of cytokines were measured in airway cell cultures using a bead-based immunoassay.

Results: The morphology of HBE, iHNE, and aHNE cell cultures were comparable, but RSV replication and spread were more prominent in HBE and iHNE compared to aHNE. Among the 13 cytokines measured, we detected significant concentrations of six cytokines: interleukin (IL)-6, IP-10, interferon (IFN)-λ1, IL-8, IFN-λ2/3, and IFN-β. Concentrations of IL-6, IFN-λ1, IFN-λ2/3, IFN-β, and IP-10 were significantly higher in HBE cell cultures than in aHNE and/or iHNE cell cultures. However, there were no differences in the cytokine concentrations measured in the aHNE and iHNE cell cultures.

Conclusion: We established methods for obtaining, culturing, differentiating, and infecting iHNE cells, which were safe and highly reproducible. A more efficient RSV replication in infants upper airway cells than in cells from adults could be a factor contributing to the greater disease severity of RSV in infants.

Coronavirus disease 2019 (COVID-19) vaccine has been extended to children 6 months and older and boosters to those 12 years and older, and vaccine safety continues to be monitored. A 12-year-old female presented with non-oliguric acute kidney injury 6 days after receiving the second dose of Pfizer COVID-19 vaccine. Renal biopsy revealed idiopathic severe acute tubulointerstitial nephritis (TIN), which had a temporal relationship with the second dose of the COVID-19 vaccine. Patient received pulse methylprednisolone (30 mg/kg) intravenous for 3 days with improvement of kidney function, followed by prednisone at 60 mg oral daily for 6 weeks. After discontinuation of corticosteroids, kidney function worsened and treatment was initiated with mycophenolate mofetil (MMF). Kidney function improved after starting MMF. Patient remained on MMF for a year and then tapered. Kidney function remained normal without any proteinuria one year after MMF was discontinued. We present a case of acute TIN after a second dose of the Pfizer COVID-19 vaccine in the United States. As this adverse outcome is less frequently reported in the U.S. than other countries, does TIN have a stronger temporal (not causal) association with a certain COVID-19 vaccine or protocol? This has implications for future COVID-19 vaccine use.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic led to the rapid development of vaccines to control the spread of infection. The inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Sinopharm BIBP vaccine was introduced in the United Arab Emirates (UAE) and registered by the Ministry of Health and Prevention before the final data of the phase III clinical trial was released. Hence, a post-authorization effectiveness and safety study was required to evaluate the effectiveness and safety profile of the vaccine.

Materials and methods: An observational Phase IV study was conducted in Sheikh Khalifa Medical City, UAE, for 18 months. The effectiveness of the BIBP vaccine was evaluated in individuals who received at least the first 2 doses and those who received the full vaccine course (with booster dose) based on immunogenicity assessment of anti-SARS-CoV-2 antibodies and protection against COVID-19.

Results: About 96% of the participants showed positive results for the neutralizing antibody and anti-S antibody against the SARS-CoV-2, 14 days after the second dose of the vaccine. The participants showed similar positive results after the booster vaccine, and the antibodies remained at that level at the one-year follow-up. Only 16 participants who received at least one dose of the vaccine experienced COVID-19. Safety outcomes showed that all serious adverse events reported were unrelated to the vaccine. No death was reported in this study period.

Conclusion: The inactivated BIBP Sinopharm vaccine proved safe and effective in protecting against COVID-19.

Zika virus (ZIKV) infection as a cause of microcephaly and Guillain-Barré syndrome gained international attention during the 2015-2016 ZIKV epidemic in the Americas. However, over ten years later, there are still no approved ZIKV vaccines, leaving people worldwide defenseless against continued disease spread and potential outbreaks. Prospects for the assessment, licensing, and commercial viability of ZIKV vaccines are complicated by the low incidence of the virus infection at the moment and the uncertainty of future outbreaks. Here, we highlight recent advances in various vaccine platforms that have been developed against ZIKV, including inactivated vaccines, live-attenuated vaccines, DNA vaccines, mRNA vaccines, viral vector vaccines, and recombinant subunit vaccines, with several candidates progressing into clinical trials. This review provides an overview of the current status of ZIKV vaccine development and emphasize how these multiple vaccine platforms can be a powerful tool to react quickly to future pandemics.

Respiratory syncytial virus (RSV) maternal vaccination has emerged as a preventive strategy to confer passive immunity to newborn during their early vulnerable months of life. In this review, we aim to assess the efficacy and safety of maternal RSV vaccines. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines for systematic reviews and meta-analyses. Our literature search covered MEDLINE via PubMed, Scopus, Web of Science, and Cochrane. We included randomized controlled trial (RCTs) that assessed the safety and efficacy of maternal RSV vaccines. The overall effect estimates for efficacy outcomes, including RSV-associated lower respiratory tract infection (LRTI), severe LRTI, and hospitalizations, demonstrated statistically significant benefits favoring the maternal RSV vaccine group (risk ratio [RR], 0.44, 95% confidence interval [CI], 0.31, 0.62, p=0.0001; RR, 0.30, 95% CI, 0.19, 0.48, p=0.0001; RR, 0.53, 95% CI, 0.37, 0.75, p=0.0004, respectively). Additionally, no statistically significant differences were identified for fetal or neonatal safety outcomes, including congenital abnormalities, intrauterine growth restriction, stillbirth, or infant death. Regarding preterm birth, the overall effect estimate did not show a significant difference between the vaccine and control groups (RR, 1.16, 95% CI, 0.96, 1.41, p=0.12). Maternal RSV vaccination provides protection against RSV-associated lower respiratory tract illness in infants with no major safety concerns. However, current evidence remains limited, and additional data from high-quality RCTs are required to confirm or refute these findings.

Trial registration: PROSPERO Identifier: CRD42024541771.

The 9-valent human papillomavirus vaccine (9vHPV) protects against 9 HPV genotypes linked to cervical cancer and genital warts. While rare, HPV vaccines may trigger autoimmune reactions. Alopecia areata (AA) is a chronic autoimmune disease that causes non-scarring alopecia. Similarly, the development of AA induced by vaccines is a rare occurrence. This report presents a case of a healthy female who developed alopecia universalis after 9vHPV vaccination, aiming to document the event, share treatment, and highlight the need for prompt medical attention.

The coronavirus disease 2019 pandemic has accelerated the global adoption and development of messenger RNA (mRNA) vaccine technology. While traditional manufacturing approaches rely on centralized and batch-based processes that are limited in scalability and accessibility, recent innovations in modular, decentralized, and continuous-flow production systems offer promising alternatives. This review summarizes the evolution of mRNA manufacturing, examines technological advances such as BioNTech's BioNTainer and Quantoom's Ntensify, and critically evaluates persistent barriers including raw material supply, regulatory compliance, sustainability, and cold-chain requirements. The implementation of artificial intelligence, thermostable formulations, and self-amplifying mRNA technologies are discussed as future directions. Collectively, these innovations offer a pathway to equitable, scalable, and rapid vaccine deployment in the context of both pandemics and routine immunization.