Vaccine最新文献

Background: COVID-19 can be severe in children with acute leukaemia (AL), significantly delaying chemotherapy. This is the first study to address the safety and immunogenicity of BNT162b2 in children with AL.

Methods: The PACIFIC trial (NCT04969601) was a phase 1/2 dose-finding study in children aged <15 years with AL and their siblings. Two doses of BNT162b2 vaccine were administered 21 days apart. The co-primary endpoints were safety, assessed by dose-limiting toxicity, and humoral immunogenicity, defined by an anti-Spike IgG titer ≥260 BAU/ml one month after the second injection. A third dose of vaccine was administered to children with an anti-Spike IgG titer <260 BAU/ml. Humoral and cellular immune responses were assessed for 12 months after the first vaccine injection.

Results: Sixty-one patients and 15 siblings were included. No toxicity was observed during dose escalation. Thus, 44/53 children received the 30 μg vaccine dose. Two months after the first injection, the humoral response was lower in patients than siblings (52 % vs 100 %, p < 0.001), whereas the T-cell response was similar in the two groups (80 % versus 100 %, p = 0.1). A significant humoral response was observed in 43 % of patients after the third dose. Both humoral and Covid-19-specific T-cell responses persisted for at least one year after vaccination. No severe Covid-19 occurred during the study.

Conclusions: Vaccination of children with acute leukaemia with adult doses (30 μg) of BNT162b2 is well tolerated and results in significant T-cell response children with AL, even during chemotherapy. As doses of 10 μg is currently recommended for children, these results support the value of increasing vaccine doses in immunocompromised patients.

Background: The need for SARS-CoV-2 vaccines with improved potency, lower reactogenicity, broader coverage, and prolonged protection persists. We examined the safety and immunogenicity of two ferritin scaffold-based self-assembling SARS-CoV-2 mRNA virus-like particle (VLP) vaccines.

Methods: In this, randomized, Phase I, open-label, active-controlled study (www.

Clinicaltrials: govNCT06147063) participants received a single 5 μg or 10 μg intramuscular injection of AZD9838 (BA.4/5 variant) or AZD6563 (XBB.1.5 variant), or 30 μg BNT162b2, a licensed mRNA vaccine (XBB.1.5 variant). The primary safety endpoint was the incidence of solicited adverse reactions (ARs) through Day 8, unsolicited adverse events (AEs) through Day 29, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) through Day 361. The primary immunogenicity endpoint was to characterize the neutralizing antibody (nAb) responses to the ancestral and Omicron (BA.4/5, XBB.1.5) variants at Day 29; characterization of nAb response to Omicron JN.1 was an exploratory analysis.

Results: In total, 166 participants aged 18-64 years and 76 participants ≥65 years of age were vaccinated. AZD9838 and AZD6563 were well-tolerated at both dosages. Overall, fewer solicited ARs were reported with AZD9838 and AZD6563 versus BNT162b2. Unsolicited AEs were similar between groups; no related SAEs, AESIs, or MAAEs were reported to Day 180. Day 29 nAb GMTs were higher following 10 μg AZD6563 versus 5 μg and higher than AZD9838 across variants and age groups, remaining above baseline and similar to BNT162b2 at Day 180; 10 μg AZD6563 resulted in nAb GMTs similar to BNT162b2 in both age groups.

Conclusion: By combining mRNA vaccine technology with VLP-based antigen display, we developed two candidate SARS-CoV-2 vaccines, AZD9838 and AZD6563, that were well tolerated versus a licensed mRNA vaccine, BNT162b2. Furthermore, the variant-matched AZD6563 generated a similar immunogenicity to BNT162b2 but at one third of the dosage (10 μg versus 30 μg).

Background: In Australia, human papillomavirus (HPV) vaccination is routinely offered at age 12-13 years through school-based programs managed by eight states and territories. Coverage has declined since the onset of the COVID-19 pandemic, with widening equity gaps. In February 2023, Australia moved from a two-dose to a single-dose HPV course. While the move was expected to increase coverage, single-dose coverage declined in the school cohort offered vaccination in 2023. We aimed to document the experience of implementing single-dose HPV vaccination and understand the current challenges in school-based immunisation programs.

Methods: In September 2024, we interviewed 11 state and territory senior immunisation staff online about their experiences implementing single-dose HPV vaccination and about current challenges in their programs. We identified categories and themes using thematic analysis.

Results: Factors that facilitated the shift to a single dose included clear and consistent communication once the change was announced, acceptance of the change by parents and providers and the increased flexibility in timing for school visits that a single-dose course provides. The main challenge related to the short timeline and a delayed ability to communicate the upcoming change due to government confidentiality requirements. This resulted in frustration, a need to retrospectively adapt consent forms and vaccine oversupply. Current challenges in the school-based immunisation programs include declining school attendance, staffing, competing priorities in schools, evolving consent processes in the digital era and increasing challenges in engaging parents and students in immunisation.

Conclusions: While implementing the change was straightforward, the shift to a single-dose occurred in a setting of increasing challenges to routinely providing immunisation in schools. Simplifying the HPV vaccination schedule may have inadvertently reduced in-school opportunities for vaccination by only requiring one annual visit. School-based vaccination programs should consider additional strategies to support catch-up vaccination and publicise options for vaccination outside of the school program.

Objective: In Norway, infant pertussis vaccination is scheduled by birth date, whereas primary school and adolescent boosters are administered to entire school classes during the 2nd and 10th school years, respectively. The interval between infant vaccination and primary school booster can thus vary from 5.5 to 7.5 years. To examine the timing of the primary school booster, we estimated pertussis incidence among children aged 2 to18 years.

Methods: We conducted a nationwide, registry-based retrospective cohort study of children born between January 1, 1998, and December 31, 2013, who had completed infant pertussis vaccination by the age of two years. We calculated incidence rates (IR) by school year and stratified by birth period (spring or autumn). We compared the average number of reported pertussis cases during the first two school years (ages 5.5-8.5) across the current schedule and two hypothetical scenarios: vaccination prior to 2nd school year or prior to school entry.

Results: Of 782,875 children eligible for the primary school booster 93% were vaccinated by the end of the 2nd school year. Pertussis incidence rose after school entry, peaking around 15 reported cases per 10,000 children annually, then declined to 5 following booster uptake. We estimated that advancing the primary school booster prior to the 2nd or 1st school year would reduce incidence by roughly 25% and 62%, respectively. Spring-born children had higher incidence rates than autumn-born peers, reflecting longer average intervals between infant and primary booster dose.

Conclusion: The current timing of the primary school pertussis booster appears suboptimal. Advancing the booster prior to the first school year could significantly reduce the burden of pertussis during first years of primary school.

Background: The herpes zoster (HZ) vaccination coverage remains low and existing research is limited. This study aimed to investigate factors associated with vaccination coverage and reasons for vaccination/non-vaccination across economic levels among individuals aged ≥50 in Zhejiang province.

Methods: A cross-sectional survey was conducted from March to May 2024 using multistage convenience sampling method. 10,500 individuals were recruited from 175 community health centers or township hospitals across 35 counties in Zhejiang Province. Chi-square test and multivariate logistic regression were used to analyze factors associated with vaccination coverage.

Results: Among 10,500 participants (mean age: 65.08), the vaccination coverage was 1.93%. Higher education level (college or higher vs primary school or below: OR = 2.609, 95% CI: 1.703-3.996) and doctor's recommendation (OR = 7.311, 95% CI: 5.032-10.621) were key factors associated with higher vaccination coverage. Among participants, vaccination motivations varied by monthly income: family recommendation and community promotion were the main drivers for those with incomes <5000 yuan, whereas "Someone close has had HZ" was most common for those with incomes ≥5000 yuan. The main non-vaccination reason for adults with monthly income of ≤10,000 yuan was "lack of vaccine knowledge", while "Unnecessary to get vaccinated" was the primary reason for the >10,000 yuan group. Television (64.64%), doctor (59.81%), and family member (50.92%) were the main ways of obtaining vaccine information, and individuals aged ≥70 years preferred to obtain vaccine information from family members compared to those aged 50-59 and 60-69 years.

Conclusion: HZ vaccination coverage among individuals aged ≥50 in Zhejiang Province remains low, with higher education and doctor's recommendation identified as key facilitators. A multifaceted strategy is recommended to improve coverage, including targeted health education via trusted channels like television, integrating vaccine prescriptions into clinical practice, and government-subsidized programs to ensure equitable access and reduce disease burden.

Brucellosis is a globally significant zoonotic disease that affects both animals and humans. Current vaccines against Brucella abortus (B. abortus), such as A19, suffer from several limitations, including residual virulence in animals and humans and the inability to serologically differentiate infected from vaccinated animals. Here, we describe attenuated strains that match the protective efficacy of the current vaccine but offer a substantially improved safety profile and enable differentiation from infection, addressing key limitations that have hampered current control tools. We constructed a double-gene deletion mutant (A19ΔfeuPΔfeuQ) from A19 by removing genes encoding a two-component regulatory system (TCS) located on chromosome II. The A19ΔfeuPΔfeuQ mutant exhibited a >1.5-log reduction in intracellular survival and BALB/c mice, indicating marked attenuation. Vaccination with this mutant induced significantly higher titers of IgG, and provided a 2.34-log greater reduction in bacterial burden at 4 weeks post-challenge. Additionally, the FEUP and FEUQ proteins served as specific antigens enabling serological differentiation between infected and vaccinated animals. These findings demonstrate that the highly attenuated A19ΔfeuPΔfeuQ mutant is a promising live vaccine candidate against bovine brucellosis, combining efficacy, improved safety, and diagnostic compatibility.

Following the emergence of SARS-CoV-2, a global consensus arose on the need for a vaccine capable of protecting the human population from both known and unknown coronavirus threats. In April 2024, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Center for Infectious Disease Research and Policy (CIDRAP) hosted a workshop to establish use cases for broadly protective coronavirus vaccines, using a pan-sarbecovirus vaccine candidate for prevention of SARS-CoV-X as an example. Workshop participants discussed implementation strategies and ideal product characteristics of pan-sarbecovirus vaccines that could be readily deployed within 100 days of SARS-CoV-X emergence. Here, we summarize the outputs from the workshop, which include the established use cases, as well as key considerations for research and development of pan-sarbecovirus vaccine candidates with characteristics to meet global needs. These use cases will be used to guide future investments and advance pandemic preparedness in line with CEPI's mission to develop safe, effective, globally accessible vaccines in as little as 100 days.

Objectives: Despite the availability of enterovirus type 71 (EV71) vaccines, evidence on long-term protection remains limited. We aimed to establish a mathematical model for predicting the 20-year long-term protection of the EV71 vaccine.

Methods: We utilized data from a phase 3 trial in which infants and young children were randomized to receive either two doses of 400 U EV71 vaccine or placebo. Neutralizing antibody data (NTAb) were obtained from the immunogenicity subpopulation who were followed for 5 years. We compared candidate decay models using Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC), and selected the Segmented Power-law Model to fit antibody decay kinetics. Simulated datasets were generated via 10,000 iterations of Bootstrap sampling. We introduced dynamic exposure simulation with differential exposure rates before and after 2017, and applied a Scaled Logit Model to establish the association between NTAb titers and protective efficacy. Additionally, we performed stratified analysis by dividing the population into High, Medium, and Low responders based on initial antibody titers. Uncertainty was quantified using 95% confidence intervals (CI).

Results: The predicted geometric mean titers (GMT) were 168.30 (95% CI: [139.76, 202.67]) at Month 1, 111.28 (95% CI: [93.15, 132.95]) at Month 6, 93.80 (95% CI: [79.12, 111.20]) at Month 12, and 68.04 (95% CI: [60.38, 76.68]) at Month 240. The model predicts that the EV71 vaccine provides a protective efficacy of 80.19% (95% CI: [78.69%, 81.70%]) at Month 1, declining to 72.57% (95% CI: [71.35%, 73.80%]) at Year 20. Stratified analysis revealed that High Responders maintained 75.58% protection at Year 20, compared to 65.09% for Medium and 64.99% for Low Responders.

Conclusion: Under the current EV71 epidemic conditions in China, the two-dose regimen of the inactivated EV71 vaccine provides durable protection exceeding 72% for at least 20 years.

The widespread and endemic nature of recent highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b outbreaks has driven increased vaccine demand. In this study, we used a Newcastle disease virus (NDV) vector expressing clade 2.3.4.4b H5 hemagglutinin (rK148/22-H5) to evaluate the efficacy of a single-dose vaccine administered via dual routes. We vaccinated 1-day-old broilers and randomly assigned them to HPAIV and viscerotropic velogenic NDV (vvNDV) challenges every 10 days. In the control group, maternal NDV antibodies waned by 20 days of age, whereas the antibody levels were sustained in the vaccinated group. Antibodies against HPAIV were first detected at 20 days post vaccination (dpv). Starting at 20 dpv, protection rates exceeded 70% and 90% against vvNDV and HPAIV challenges, respectively. Notably, at 30 dpv, no virus shedding was detected in the oropharyngeal and cloacal tissues following highly pathogenic avian influenza challenge. The rK148/22-H5 vaccine administered via the dual route is a promising candidate for single-dose vaccination to effectively protect young chicks against HPAIV and vvNDV.

Objectives: The Bacillus Calmette-Guerin (BCG) vaccine has beneficial effects on the immune system, which may lead to non-specific protection against non-tuberculous infections and increase the response to subsequent vaccinations. Seasonal influenza vaccination is used to protect senior citizens against influenza, but the serological response to the inactivated influenza vaccine (IIV) decreases in the elderly due to immunosenescence. The aim of this study was to test the capacity of BCG to boost the specific immune response to IIV and explore the effect of BCG on the innate immune system and health of senior citizens.

Methods: A randomised controlled trial with a nested immunological study including 273 Danish citizens >65 years. Participants were randomised into four equally sized groups combining BCG with IIV in different sequences compared with IIV alone. The primary outcome was change in influenza antibody hemagglutination inhibition (HI) titre four weeks after vaccination. Secondary outcomes were infection rate during six months follow-up, and association between influenza antibody titre and infection rate. In subgroup analyses, we explored the effect of BCG on lymphocyte populations seven days after IIV and on cytokine production after stimulation of mononuclear cells in vitro.

Results: Four weeks after influenza vaccination, the mean fold change in HI titre over all serotypes was 2.3-2.5 with no significant differences between the treatment groups. Seroconversion rate was comparable between treatment groups, and in strata of age and sex. There was no difference in the rate of infection between the groups and there was no association with influenza antibody level. We found no difference in distribution of lymphocytes. Combining BCG with IIV had modest impact on in vitro cytokine production compared with IIV alone.

Conclusion: BCG vaccination did not increase serological response to seasonal influenza vaccination or reduce the incidence of infection in this population of Danish senior citizens.

Trial registration: EU Clinical Trials Register (EudraCT number 2019-002781-12).

Summary: In this randomised clinical trial of Danish senior citizens, BCG vaccination did not influence serological response to influenza vaccination or reduce the risk of infection compared with placebo. There was no clear indication of induction of trained immunity.