Vaccine最新文献

Objective: To evaluate febrile seizure risk following monovalent COVID-19 mRNA vaccination among children aged 2-5 years.

Methods: The primary analysis evaluated children who had a febrile seizure outcome in the 0-1 days following COVID-19 vaccination. A self-controlled case series analysis was performed in three commercial insurance databases to compare the risk of seizure in the risk interval (0-1 days) to a control interval (8-63 days). The exposure of interest was receipt of dose 1 and/or dose 2 of monovalent COVID-19 mRNA vaccinations. The primary outcome was febrile seizure (0-1 day risk interval). A conditional Poisson regression model was used to compare outcome rates in risk and control intervals and estimate incidence rate ratios (IRR) and 95% confidence intervals (CIs). Meta-analyses were used to pool results across databases.

Results: The primary meta-analysis found a statistically significant increased incidence of febrile seizure, in the 0-1 days following mRNA-1273 vaccination compared to the control interval (IRR: 2.52, 95% CI: 1.35 to 4.69, risk difference (RD)/100,000 doses = 3.22 (95% CI -0.31 to 6.75)). For the BNT162b2 vaccination, the IRR was elevated but not statistically significant (IRR: 1.41, 95% CI: 0.48 to 4.11, RD/100,000 doses = -0.25 (95% CI -2.75 to 2.24).

Conclusions: Among children aged 2-5 years, the analysis showed a small elevated incidence rate ratio of febrile seizures in the 0-1 days following the mRNA-1273 vaccination.

We assessed antibody persistence and the impact of an additional dose administered 42-60 months after initial vaccination. Girls initially vaccinated at ages 9-10 with two doses of quadrivalent HPV vaccine participated in two randomized trials: The 0-6-42HPV study which compared a quadrivalent and bivalent additional dose given at 42 months; The 0-6-60ICI-VPH study compared no additional dose to a quadrivalent dose at 60 months. HPV16/18 antibody detection and geometric mean concentrations (GMCs) were assessed (M9ELISA). Overall, 526 girls provided a blood sample. All had detectable HPV16/18 antibodies 10 years post-initial vaccination. An additional dose at 42 versus 60 months led to similar GMCs, both with higher immune responses compared to 2-dose group participants. Compared to the quadrivalent, the bivalent induced significantly higher HPV18 GMCs, which has unknown clinical significance. Two-dose schedule and delayed quadrivalent or bivalent additional doses are highly immunogenic, supporting long-term immunogenicity of alternative and mixed vaccination schedules.

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in blood in mice receiving either with TSA-1.C4 vaccine alone or in combination with a low dose of BNZ. TSA-1.C4-specific IgG and isotype levels were increased in all experimental groups receiving TSA-1.C4 protein treatment, confirming its immunogenicity. Mice treated with TSA-1.C4 vaccine in combination with BNZ exhibit a reduced cardiac inflammation as well as an antigen-specific IFN-γ CD4⁺ T cells with an IL-2 and IL-4 cytokine production. Even though TSA-1.C4 vaccine alone induced a cytokine response by IFN-γ and IL-10 production, only the TSA-1.C4 vaccine plus BNZ reduced cardiac inflammatory infiltrate compared to infected untreated mice. In conclusion the therapeutic vaccine with a low dose of BNZ prevent cardiac inflammation and provide a balanced Th1/Th2 cytokine immune response in a murine model of acute Chagas disease.

Mumps and rubella are highly contagious, vaccine-preventable diseases; however, India's National Immunization Program prioritizes rubella while excluding mumps. In this cross-sectional study, we measured mumps- and rubella-specific IgG seroprevalence in 508 children (49.6% female) from Kerala and evaluated demographic associations. Seropositivity was 78.5% (95% CI, 74.8-81.9%) for mumps and 99.4% (95% CI, 98.3-99.8%) for rubella. Mumps IgG titers were significantly higher in females (p = 0.0061) and increased with vaccine doses (p < 0.001), whereas rubella IgG titers showed no such associations (p > 0.05). IgG titers for both mumps (r = -0.13, p = 0.0043) and rubella (r = -0.23, p < 0.001) declined with time since vaccination, indicating waning immunity. The contrast between high rubella and lower mumps immunity likely reflects differences in vaccination prioritization and support the inclusion of mumps-containing vaccines into India's National Immunization Program, ideally through universal adoption of the measles-mumps-rubella (MMR) vaccine.

Hypertensive disorders of pregnancy (HDP) are leading causes of maternal and fetal morbidity/mortality. To identify potential safety concerns, we evaluated whether COVID-19 vaccination during pregnancy or within 30 days of last menstrual period was associated with self-reported HDP. We also evaluated HDP risk associated with COVID-19 illness during pregnancy. We conducted a matched cohort study using data from the Centers for Disease Control and Prevention's COVID-19 Vaccine Pregnancy Registry (C19VPR; vaccinated) and Pregnancy Risk Assessment Monitoring System (PRAMS; unvaccinated). Participants included nulliparous women with singleton pregnancies ending in livebirth (C19VPR, December 2020-March 2022; PRAMS, 2019-2021). Participants were matched by age group, race/ethnicity, and gestational age at delivery. We estimated relative risk (RR) for self-reported HDP by vaccination status using Poisson regression, adjusting for confounders. We tested for effect modification by vaccine manufacturer and vaccination timing (<20 or ≥ 20 weeks' gestation). Among matched pairs with data on self-reported COVID-19 illness in pregnancy, we estimated risk of HDP by illness status. Of 8030 eligible C19VPR participants, 8024 (99.9%) were matched to a PRAMS participant. Most C19VPR participants delivered in 2021 (98.9%); PRAMS participants delivered predominantly in 2020 (54.5%) and 2019 (17.4%). Adjusted RR for HDP was 1.24 (95% confidence interval [CI]: 1.08, 1.43) among C19VPR versus PRAMS participants. We observed no effect modification. Results of an analysis restricted to matched pairs who delivered in 2021 (n = 2231) were similar. Among matched pairs (n = 4039) with data on COVID-19 illness in pregnancy, adjusted RR for HDP was 1.28 (95%CI: 1.02, 1.60) for those reporting illness compared with no illness. Risk of HDP was higher among COVID-19 vaccinated compared to unvaccinated women; however, the two groups were sampled from different cohorts. Risk was similar to those who reported COVID-19 illness. Given cohort differences, the associations observed cannot be considered causal; updated assessments of HDP risks after illness and vaccination would be useful.

Despite decades of research, no vaccine has been approved for herpes simplex virus-2 (HSV-2). While HSV-2 subunit vaccines have been more extensively studied, various HSV-2 mutants have also been tested. We compared three types of HSV-2 mutant viruses (replication-defective, single-cycle replication, and replication-competent) using five routes of vaccination (intramuscular, subcutaneous at two different sites, intrarectal, or intravaginal) for their ability to protect mice from intravaginal challenge with HSV-2. The replication-competent virus vaccine gave the best protection compared to the other vaccines after intravaginal vaccination of mice resulting in complete prevention of disease, and 90 % of the animals had no detectable shedding after challenge despite very low serum neutralizing titers. The replication-competent virus vaccine was also superior to the other vaccines when given intrarectally, although less effective than when given intravaginally. In contrast, when given subcutaneously in the scruff of the neck, the replication-defective vaccine was more effective than the replication-competent vaccine and the replication-defective vaccine tended to be more effective than the live vaccine when given intramuscularly. The highest levels of serum neutralizing antibody were observed with the replication-defective and single-cycle replication vaccines given intramuscularly. Thus, excellent protection from genital herpes was obtained after intravaginal vaccination with the replication-competent vaccine providing evidence that a replication-competent vaccine given by the natural route of HSV-2 infection is superior to replication-defective or single-cycle replication vaccines to reduce virus infection and spread in the genital mucosa.

The repeated emergence of highly transmissive SARS-CoV-2 variants requires a broadly protective vaccine. We developed a T-cell vaccine VB10.2210 that targets SARS-CoV-2 viral antigens to antigen presenting cells comprising 96 validated immunogenic T-cell epitopes covering a global HLA diversity. We report results from a first in human open-label dose-escalation phase 1/2 clinical trial evaluating safety, reactogenicity and immunogenicity of VB10.2210. The study investigated three dose levels (0.3, 1.0 and 3.0 mg), delivered intramuscularly as DNA plasmid by jet injection (NCT05069623), in 34 healthy adults previously vaccinated with mRNA SARS-CoV-2 vaccines. The safety profile was favorable with no observed dose-limiting toxicity. The 3 mg dose elicited the most potent immune response with enhanced breadth and a CD8+ dominated T cell response. T cell responses towards spike protein and de novo responses to non-spike antigens were confirmed by ELISpot. Expansion of VB10.2210 specific T-cell clones was confirmed by TCR sequencing. Further studies are needed to evaluate the clinical benefit of DNA vaccines inducing broad virus specific T-cell immunity in preventing severe COVID-19 or as treatment of patients with persistent infection.

Identifying conserved, immunogenic proteins that confer protection against Streptococcus pneumoniae (pneumococcus) colonization could enable development of serotype-independent vaccines. In our controlled human infection model, no individual IgG or cytokine/chemokine response correlated significantly with protection against colonization with pneumococcus, suggesting that effective immunity reflects a coordinated, multi-antigen response. To capture these complex patterns, we trained independent Random Forest models on humoral and cellular datasets. The humoral model identified IgG responses to PdB, SP1069, and SP0899 as predictive of protection. The cellular model revealed that MCP-1 responses to SP1069 and SP0899, and IL-17A production in response to SP0648-3, were associated with protection. Elevated baseline IFN-γ, RANTES, and anti-protein IgG levels were linked to reduced colonization density. We highlight SP1069 and SP0899 as potential serotype-independent vaccine candidates and demonstrate the utility of machine learning to identify immune correlates of protection.