BACKGROUND: During the 2022-23 season, three autonomous communities recommended influenza vaccination for all children between 6 and 59 months. The objective is to evaluate the adverse effects associated with the administered influenza vaccines in the Region of Murcia, as well as their influence on the recommendation of the same to acquaintances or repetition in future seasons.
METHODS: Cross-sectional descriptive study with an online questionnaire sent to the parents of vaccinated minors of 6-23 months of age receiving inactivated intramuscular vaccine (IIV) or 24-59 months of age receiving live-attenuated intranasal vaccine (LAIV).
RESULTS: Among 4971 surveys received, the most common adverse effect for LAIV and IIV was runny nose (40.90%) and local pain (31.94%), respectively. Sixty percent of adverse effects lasted ≤ 1 day, and around 10% lasted ≥ 3 days. The interference of adverse effects with the minor\'s daily life was very infrequent (3.32%), as was the need for visiting the medical office (2.68%). Overall, 96.44% of parents would recommend influenza vaccination to friends and relatives after the experience. Only 3.56% would not recommend it, while 1.68% would not vaccinate their child against influenza again. The most frequently cited reason being adverse effects.
CONCLUSIONS: Our study shows the safety of influenza vaccines. Despite the low impact of adverse effects, they influence some parents in their intention to continue vaccinating or recommending it to acquaintances, which remarks the need to reinforce the information given to parents so that this fact does not influence decision-making.

BackgroundTick-borne encephalitis (TBE) is a severe, vaccine-preventable viral infection of the central nervous system. Symptoms are generally milder in children and adolescents than in adults, though severe disease does occur. A better understanding of the disease burden and duration of vaccine-mediated protection is important for vaccination recommendations.AimTo estimate TBE vaccination coverage, disease severity and vaccine effectiveness (VE) among individuals aged 0-17 years in Switzerland.MethodsVaccination coverage between 2005 and 2022 was estimated using the Swiss National Vaccination Coverage Survey (SNVCS), a nationwide, repeated cross-sectional study assessing vaccine uptake. Incidence and severity of TBE between 2005 and 2022 were determined using data from the Swiss disease surveillance system and VE was calculated using a case-control analysis, matching TBE cases with SNVCS controls.ResultsOver the study period, vaccination coverage increased substantially, from 4.8% (95% confidence interval (CI): 4.1-5.5%) to 50.1% (95% CI: 48.3-52.0%). Reported clinical symptoms in TBE cases were similar irrespective of age. Neurological involvement was less likely in incompletely (1-2 doses) and completely (≥ 3 doses) vaccinated cases compared with unvaccinated ones. For incomplete vaccination, VE was 66.2% (95% CI: 42.3-80.2), whereas VE for complete vaccination was 90.8% (95% CI: 87.7-96.4). Vaccine effectiveness remained high, 83.9% (95% CI: 69.0-91.7) up to 10 years since last vaccination.ConclusionsEven children younger than 5 years can experience severe TBE. Incomplete and complete vaccination protect against neurological manifestations of the disease. Complete vaccination offers durable protection up to 10 years against TBE.

UNASSIGNED: Vaccines are the most cost-effective and straightforward intervention against severe infectious diseases. However, in Europe and in Italy, paediatric vaccination coverage for certain vaccines remains suboptimal, with considerable regional differences in Italy. Vaccine coverage varies significantly due to socio-economic and organisational factors. Aim of this study was to assess the influence of the Deprivation Index, the density of General Practitioners and General Paediatricians per inhabitants on the coverage of both mandatory and non-mandatory paediatric vaccinations across local health authorities and health districts in the Campania Region for birth cohorts from 2001 to 2015.
UNASSIGNED: Population-based, ecological time series analysis focusing on the Campania Region, most populous region in the south of Italy. Vaccination coverage data were extracted from the regional immunization database, whilst information on the Deprivation Index and number of primary care doctors and primary care paediatricians per local health district were extracted from public health records. Univariate descriptive statistics were employed to describe study characteristics, as appropriate, whilst and mixed-effect linear regression models were employed to assess the associations between variables of interest and vaccination coverage.
UNASSIGNED: Overall vaccination coverage has generally increased, except for the MMR vaccine, which showed coverage fluctuations. An increase in the Deprivation Index, indicative of less favourable socio-economic conditions, was associated with decreased vaccination coverage in the 24-month age group for some mandatory vaccines (DTaP: Coef -0.97, 95% CI -1.77 | -0.17; Poliomyelitis: Coef -0.98, 95% CI -1.78 | -0.17; Hepatitis B: Coef -0.90, 95% CI -1.71 | -0.10). Moreover, areas with a greater density of General Paediatricians per inhabitants saw increased coverage for Haemophilus influenzae type b in the 6-year age group (Coef 9.78, 95% CI 1.00 | 18.56).
UNASSIGNED: It is necessary to target public health policies to address vaccination inequalities. These efforts should include expanding vaccination campaigns, enhancing catch-up programs, and increase resource allocation in primary care settings to facilitate the role of General Practitioners and Paediatricians in fostering awareness and adherence.

Vaccines can have beneficial off-target (heterologous) effects that alter immune responses to, and protect against, unrelated infections. The heterologous effects of COVID-19 vaccines have not been investigated in children.
To investigate heterologous and specific immunological effects of BNT162b2 COVID-19 vaccination in children.
A whole blood stimulation assay was used to investigate in vitro cytokine responses to heterologous stimulants (killed pathogens, Toll-like receptor ligands) and SARS-CoV-2 antigens. Samples from 29 children, aged 5-11 years, before and 28 days after a second BNT162b2 vaccination were analysed (V2 + 28). Samples from eight children were analysed six months after BNT162b2 vaccination.
At V2 + 28, interferon-γ and monocyte chemoattractant protein-1 responses to S. aureus, E. coli, L. monocytogenes, BCG vaccine, H. influenzae, hepatitis B antigen, poly(I:C) and R848 stimulations were decreased compared to pre-vaccination. For most of these heterologous stimulants, IL-6, IL-15 and IL-17 responses were also decreased. There were sustained decreases in cytokine responses to viral, but not bacterial, stimulants six months after BNT162b2 vaccination. Cytokine responses to irradiated SARS-CoV-2, and spike glycoprotein subunits (S1 and S2) were increased at V2 + 28 for most cytokines and remained higher than pre-vaccination responses 6 months after BNT162b2 vaccination for irradiated SARS-CoV-2 and S1. There was no correlation between BNT162b2 vaccination-induced anti-SARS-CoV2-receptor binding domain IgG antibody titre at V2 + 28 and cytokine responses.
BNT162b2 vaccination in children alters cytokine responses to heterologous stimulants, particularly one month after vaccination. This study is the first to report the immunological heterologous effects of COVID-19 vaccination in children.

To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children.
This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-μg) or half-dose (5-μg) BNT162b2 vaccines as follows: CoronaVac/10-μg-BNT162b2 (Group 1), CoronaVac/5-μg-BNT162b2 (Group 2), 10-μg-BNT162b2/10-μg-BNT162b2 (Group 3), or 10-μg-BNT162b2/5-μg-BNT162b2 (Group 4). A subset of participants from each arm received 10-μg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported.
Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter.
Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines.

The current pediatric vaccination program in England and Wales administers Live-Attenuated Influenza Vaccine (LAIV) to children ages 2-16 years old. Annual administration of LAIV to this age group is costly and poses substantial logistical issues. This study aims to evaluate the cost-effectiveness of prioritizing vaccination to age groups within the 2-16 year old age range to mitigate the operational and resource challenges of the current strategy. We performed economic evaluations comparing the influenza vaccination program from 1995-2013 to seven alternative strategies targeted at low risk individuals along the school age divisions Preschool (2-4 years old), Primary school (5-11 years old), and Secondary school (12-16 years old). These extensions are evaluated incrementally on the status quo scenario (vaccinating subgroups at high risk of influenza-related complications and individuals 65+ years old). Impact of vaccination was assessed using a transmission model from a previously published study and updated with new data. At all levels of coverage, all strategies had a 100% probability of being cost-effective at the current National Health Service threshold, £20,000/QALY gained. The incremental analysis demonstrated vaccinating Primary School children was the most cost-efficient strategy compared incrementally against others with an Incremental Cost-Effectiveness Ratio of £639 spent per QALY gained (Net Benefit: 404 M£ [155, 795]). When coverage was varied between 30%, 55%, and 70% strategies which included Primary school children had a higher probability of being cost-effective at lower willingness-to-pay levels. Although children were the vaccine target the majority of QALY gains occurred in the 25-44 years old and 65+ age groups. Influenza strain A/H3N2 incurred the greatest costs and QALYs lost regardless of which strategy was used. Improvement could be made to the current LAIV pediatric vaccination strategy by eliminating vaccination of 2-4 year olds and focusing on school-based delivery to Primary and Secondary school children in tandem.

The \"vaccine hesitancy\" and the consequent lowering of vaccination coverage have, on one hand, pushed the Italian government to reintroduce some new compulsory vaccinations for access to schools and, on the other, have imposed a greater effort on health operators to understand the causes and, consequently, to intervene with tools for promotion and health education. In Ferrara, we administered 201 non-self-filling questionnaires to 201 pregnant women within a cross-sectional multicenter study, consisting of 63 items divided into 7 sections. In particular, we wanted to investigate the correlation between the socio-demographic characteristics of the interviewees and the sources used to obtain information and, on the other side, the intention to vaccinate in relation to the perception of the diffusion and of the risk of vaccine-preventable diseases. The institutional information sources are less used by foreigners, primiparous, and women with a low education level. The perception of the severity of vaccine-preventable diseases was greater in those inquiring from institutional sources. In a public health perspective, knowing the profile of future mothers in terms of socio-demographic characteristics and of the quality of the used information channels may help to guide the choices of communication in the vaccination field.

Immunization of adolescent girls with VLP vaccines, made of L1 proteins from the most medically significant high risk HPV types, is a major strategy for prevention of cervical cancer plus other HPV-associated cancers. Maximal population impact, including through herd immunity, requires high vaccination coverage. However, protection of unvaccinated women requires secondary prevention through cytology screening. Unfortunately in countries with the highest incidence/mortality due to cervical cancer HPV vaccination (or cytology screening) is not sufficiently available. Vaccination programme costs and a lack of accessibility of the populations for immunization remain significant hurdles. Several approaches could increase effective implementation of HPV vaccination. 1) Use of a single immunization of the current VLP vaccines. 2) Vaccination bundled with other paediatric vaccines with lower dosage to facilitate delivery, improve coverage and reduce costs through established logistics. 3) Local manufacture with lower cost systems (e.g. bacteria) for VLP or capsomer based vaccine production and utilization of additional protective epitopes (e.g L2) for increasing breadth of protection. However, all the latter need appropriate clinical validation. Gender neutral vaccination and extending routine vaccination strategies to women up to age 30 years in combination with at least one HPV screening test can also hasten impact on cancer incidence.

Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines.
In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 8-10 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 30 µg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 µg of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination.
1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, ≥97.4% (3+0 schedule) and ≥96.4% (2+1 schedule) of infants had antibody concentrations ≥0.2 μg/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns.
Immune responses to the 10 PHiD-CV polysaccharide conjugates and co-administered vaccines were not altered by addition of dPly and PhtD. ClinicalTrials.gov identifier NCT01262872.

On-going post-licensure surveillance of adverse events following immunisation (AEFI) is critical to detecting and responding to potentially serious adverse events in a timely manner. SmartVax is a vaccine safety monitoring tool that uses automated data extraction from existing practice management software and short message service (SMS) technology to follow-up vaccinees in real-time. We report on childhood vaccine safety surveillance using SmartVax at a medical practice in Perth, Western Australia.
Parents of all children under age five years who were vaccinated according to the Australian National Immunisation Schedule between November 2011 and June 2015 were sent an SMS three days post administration to enquire whether the child had experienced a suspected vaccine reaction. Affirmative replies triggered a follow-up SMS requesting details of the reaction(s) via a link to a survey that could be completed using a smartphone or the web. Rates of reported AEFI including fever, headache, fatigue, rash, vomiting, diarrhoea, rigours, seizures, and local reactions were calculated by vaccination time point.
Overall, 239 (8.2%; 95% CI 7.2-9.2%) possible vaccine reactions were reported for 2897 vaccination visits over the 44 month time period. The proportion of children experiencing a possible AEFI, mostly local reactions, was significantly greater following administration of diphtheria-tetanus-pertussis-poliomyelitis vaccine at 4 years of age (77/441; 17.5%; 95% CI 13.9-21.0%) compared to the vaccinations given at 2-18 months (p<0.001). Across all time points, local reactions and fatigue were the most frequently reported AEFI.
Automated SMS-based reporting can facilitate sustainable, real-time, monitoring of adverse reactions and contribute to early identification of potential vaccine safety issues.