Clinical and Experimental Vaccine Research最新文献

Herpes B virus (BV) is enzootic to macaques and represents a significant zoonotic threat to humans. In macaques, the viral infection is typically latent and asymptomatic, however, BV can become a deadly neurotropic infection in humans, commonly leading to encephalomyelitis. Although seroprevalence among macaques is widespread, particularly in wild-caught or laboratory-maintained populations, zoonotic transmission has remained rare since the first documented case. The limited host range of BV contrasts with its ability to cross species barriers under specific conditions. Diagnostic challenges and delayed symptom onset can interrupt early detection and antiviral treatment. Thus, BV is a paramount concern in the context of primate research and captive animal care. Consequently, this threat will require international collaboration, comprehensive surveillance, and continued researches to prevent zoonotic transmission and maintain safe primate research environments.

The occurrence of Guillain-Barré syndrome (GBS) following coronavirus disease 2019 (COVID-19) vaccination have been documented; however, its pathogenesis remains unclear. We present a case of GBS associated with T-cell receptor (TCR) clonal rearrangement after COVID-19 vaccination. A previously healthy 60-year-old man developed fever, skin rash, general fatigue, and generalized urticaria after receiving his third vaccine dose (Spikevax, Moderna). No adverse events occurred after his first and second doses (COMIRNATY, Pfizer). Within 4 weeks of vaccination, the patient experienced progressive limb weakness and gait instability, and was referred to our hospital. Nerve conduction studies revealed increased distal latency, reduced compound muscle action potential amplitudes, decreased motor nerve conduction velocities, and diminished sensory nerve action potentials. Positron emission tomography-computed tomography showed systemic lymphadenopathy, splenomegaly, and increased splenic and bone marrow uptake. Bone marrow biopsy and peripheral blood analysis demonstrated TCR clonal rearrangement, which resolved by day 115 post-vaccination. Based on clinical progression, electrophysiological findings, and worsening neurological symptoms, a diagnosis of GBS was made. This case suggests that aberrant T-cell clonal expansion may contribute to GBS development following COVID-19 vaccination. To our knowledge, this is the first report describing TCR gene clonal rearrangement following COVID-19 vaccination.

Rabies is a fatal zoonotic disease primarily transmitted through dog bites, making oral rabies vaccines critical for disease control. This study evaluated the immunogenicity of the ERAGS-GFP oral rabies vaccine strain in dogs. To optimize viral production, we examined cell density, multiplicity of infection (MOI), and freeze-thaw cycles. Safety was assessed via clinical monitoring, body temperature, and weight changes. Immunogenicity was evaluated using rabies virus neutralizing antibody (VNA) titers. Vero cells at MOI 2 with 3 freeze-thaw cycles yielded the highest viral titers. Vaccinated dogs showed no clinical symptoms and developed sustained protective VNA titers, demonstrating ERAGS-GFP's efficacy in rabies control.

Purpose: Mast cell activating adjuvants induce vaccine-specific systemic and mucosal immunity when administered intranasally. Bordetella pertussis infects the respiratory tract and caused 0.45% childhood mortality in the United States before implementing pertussis vaccines. Pertussis infections are resurging. Immunity induced by current pertussis vaccines wanes quickly, possibly due to vaccine-induced T helper (Th) 2 and weak mucosal immunity. B. pertussis induces Th1, Th17, and mucosal immunoglobulin A (IgA) immunity, providing durable protection against disease. Next-generation pertussis vaccines that induce Th1, Th17, and IgA immunity may reduce the resurgence of pertussis. This study determined if nasal pertussis vaccines adjuvanted with the mast cell activator compound 48/80 (C48/80) modulate pertussis-specific immunity.

Materials and methods: Mice received intranasal C48/80-adjuvanted pertussis vaccines or subcutaneous aluminum-adjuvanted pertussis vaccines. Immunized mice were challenged with B. pertussis and monitored for protection against infection. Pertussis-specific immune profiles were characterized after immunization. A C48/80 and CpG adjuvant combination was evaluated to enhance pertussis-specific Th1 immunity.

Results: Alum-adjuvanted pertussis vaccines induce Th2 immunity and undetectable IgA responses. Nasal C48/80-adjuvanted pertussis vaccines enhance pertussis-specific serum and mucosal IgA and Th2 and Th17 responses but not Th1 immunity. The C48/80 and CpG adjuvant combination enhances systemic and mucosal pertussis-specific Th1, Th17, and IgA compared to unadjuvanted pertussis vaccines, which may be the desired immune response to protect against pertussis infections.

Conclusion: We demonstrate that nasal pertussis vaccines containing C48/80 adjuvants induce pertussis-specific IgA, Th1-, and Th17-associated immunity when combined with CpG, which may be an effective strategy to improve pertussis vaccines.

Purpose: Japanese Encephalitis Virus (JEV) is a mosquito-borne flavivirus that causes severe neurological complications and high mortality rates in Asia. Developing vaccines is crucial for controlling its spread. Liposomes, as advanced drug delivery systems, have demonstrated promise in reducing systemic toxicity and enhancing drug penetration across the blood-brain barrier. Given these advantages, this study aimed to evaluate the immunoglobulin G (IgG) antibody response to JEV antigen administered via injection and liposome-based oral delivery.

Materials and methods: The liposome-based vaccine used in this study was formulated from a custom-synthesized lipid to enhance the vaccine's efficacy. The rats were divided into 3 groups: a control group, a liposome-based injectable vaccine group, and a liposome-based oral vaccine group. Blood samples were collected at 3 and 5 weeks post-administration to measure IgG antibody levels.

Results: As expected, the control group exhibited no immune response. In contrast, liposome-based oral and injectable vaccine groups showed considerable results. The liposome-based injectable vaccine group demonstrated a strong increase in IgG levels, and the liposome-based oral vaccine group exhibited a moderate but notable rise. At 5 weeks, antibody levels in the control group returned to baseline, whereas the vaccinated groups maintained elevated levels.

Conclusion: The injectable formulation induced a stronger immune response; however, the oral formulation showed potential as an alternative. These findings suggest that refinement of the oral formulation may provide practical advantages such as ease of administration, non-invasiveness, and improved logistics. Such features could potentially contribute to broader immunization efforts, including those aimed at global disease control.

Influenza C virus (ICV) was discovered in 1947 and detected in humans, with natural infections occurring periodically. However, early studies on ICV were challenging in diagnosis because the virus is difficult to culture. As a result, the disease burden and pathogenicity of ICV have been underestimated. Recent studies using molecular biological techniques such as real-time polymerase chain reaction have provided further insights into prevalence, seasonality, genomic diversity, and evolution. In addition, the possibility of interspecies transmission was suggested based on the high similarity between the nucleotide sequence of ICV confirmed to infect animals and the sequence of ICV isolated from humans. In this review, we summarize current data on the epidemiology and clinical features, viral genome analysis, and animal studies of ICV.

Purpose: The current novel coronavirus disease pandemic was declared by the World Health Organization in 2020. Considering the difference in the infection and mortality rates in healthcare workers in Iran compared to other countries, as well as the diversity of vaccines used and their effectiveness, this study was conducted to investigate the effect of coronavirus disease 2019 (COVID-19) vaccination on the viral loads and symptoms of healthcare workers.

Materials and methods: In this retrospective cohort study, viral loads of first and breakthrough COVID-19 infections of Imam Reza and Mohammad Kermanshahi Hospital personnel were measured before and after full dose COVID-19 vaccination, through measuring delta cycle threshold (ΔCt), an inverse measure of viral load, from 2020 to 2021 in Kermanshah, Iran.

Results: Polymerase chain reaction test results of 110 cases with an average age of 35.15±8.04 were compared. Female participants were 71 (64.5%), and the rest were male. Breakthrough viral loads were significantly lower than first infection (mean ΔCt, 22.04±4.59 vs. 26.61±3, p<0.001). Cough, fever, chills, and myalgia frequencies were significantly decreased in breakthrough infections (p<0.05), except for dyspnea. Gastrointestinal symptoms remained the same, and anosmia frequency increased in breakthrough infections. Viral loads based on vaccine type and clinical symptoms were significantly reduced (p<0.05).

Conclusion: Based on our findings, 2 doses of COVID-19 vaccination could be effective in reducing the viral loads and frequency of clinical symptoms in Iranian healthcare workers.

Purpose: Tuberculosis (TB) claims around 1.5 million lives annually. The M72/AS01E vaccine candidate is an innovative effort demonstrating a 50% reduction in the incidence of active TB in adults. However, optimization and effective immunization strategies against TB depends heavily on precise identification of specific molecular signatures active in vaccine protection.

Materials and methods: In this study, we employed weighted gene co-expression network analysis, machine learning, and network biology to investigate the gene expression patterns of peripheral blood mononuclear cells, identifying transcriptomic markers of vaccine protection.

Results: Our comprehensive exploration of publicly available gene expression dataset comprising samples from subjects vaccinated twice with 10 μg of M72/AS01E vaccine one day post-second dose (D31) and one week post-second dose (D37) in a phase IIA clinical trial revealed intense induction of multiple gene modules, indicative of acute/immediate immune response at D31 that subsided by D37. Thirty-one hub genes with significant elevation/correlation with immune protection were identified significantly mediating key events in immunity to TB. The more selective profile at D37 involved additional adaptive immunity pathways including T helper (Th) 1/Th2/Th17 differentiation, T cell receptor and cytokine signaling. The functional relevance of these biomarkers in predicting vaccine response was further analyzed using the Random Forest classifier demonstrating high accuracy in distinguishing between vaccinated and non-vaccinated samples. Additionally, the study pinpointed a miRNAs-transcription factors (TF)-target regulatory network excavating key TF, miRNA, mRNAs mediating vaccine protection.

Conclusion: Our results provided new insights into M72/AS01E immunity, warranting further study to optimize and guide future TB vaccine development.

Purpose: Developing a treatment for Nipah virus (NiV) infection is necessary due to its high fatality rate, broad host range, and unavailable licensed effective treatment. Therefore, this study aimed to identify candidate epitopes of NiV proteins as immunotherapeutic agents for vaccine development.

Materials and methods: Immunoinformatics was used to identify conserved fragments and candidate CD8+ epitopes in all 6 structural (F, G, L, M, N, and P) and 2 of 3 nonstructural proteins (V and W). Potential cross-reactivity, toxicity, and allergenicity were assessed. The population coverage of each candidate epitope globally and in high-risk regions were analyzed. Selected epitope-human leukocyte antigen (HLA) pairs were docked to analyze binding energy and spontaneity and favorability of complex formation.

Results: Conservation analysis of proteins F, G, L, M, N, P, V, and W resulted in 16, 11, 40, 8, 14, 41, 10, and 10 conserved fragments (≥ nonamer), respectively. One hundred and fifty-three conserved CD8+ epitopes are promiscuous binders and are likely to be good major histocompatibility complex I binders (inhibitory concentration 50 <500 nM), non-toxic, non-allergenic, and non-cross-reactive with human antigens (E-value >1.0e-30). The 3 epitopes with the highest population coverage are ¹⁸⁷YMIPRTMLEF¹⁹⁶ (Global=69.77%, Indonesia=49.69%, Malaysia=5.38%, Philippines=88.44%), ⁶²YMYLICYGF⁷⁰ (Philippines=88.44%) from M, and ⁸⁰⁹ATIPFLFLSAY⁸¹⁹ (India=53.86%, Thailand=66.25%) from L. Molecular docking of selected CD8+ epitopes with HLA I allele binders showed favorable and spontaneous complex formation.

Conclusion: Results showed promising CD8+ T cell epitopes among the structural and nonstructural proteins of NiV, that possess safety, immunogenicity, and broad population coverage.

Purpose: Streptococcus pneumoniae is a leading global cause of morbidity and mortality, particularly in individuals with type 2 diabetes, who are at increased risk due to altered immunity. Vaccination is crucial for preventing pneumococcal disease in this population; however, its effectiveness depends on sufficient baseline immunity and the ability to generate protective antibodies.

Materials and methods: This study aimed to measure baseline immunoglobulin G (IgG) antibody levels against 23 vaccine serotypes in 56 type 2 diabetic and 56 healthy Indian adults using the World Health Organization-enzyme-linked immunosorbent assay protocol.

Results: Protective IgG levels (≥1.3 µg/mL) were observed for 78% of serotypes (18/23) in healthy adults but only 35% (8/23) in diabetics. Significant differences were noted in 13 of 23 serotypes (56.2%), including 1, 6B, 7F (p=0.008), 8 (p=0.01), 9V, 11A (p=0.009), 12F, 17F, 18C (p=0.002), 19A (p=0.0006), 19F (p=0.004), 22F (p=0.0003), and 33F (p=0.04). Serotype 14 showed the highest IgG levels, while serotype 3 had the lowest. Seroprevalence ranged from 17.8% to 98.21% in non-diabetics and 10.7% to 96.4% in diabetics.

Conclusion: The findings highlight differences in baseline immunity and provide insights into pneumococcal immunogenicity in Indian adults with and without diabetes.