Characterizing the antigenic evolution of pandemic influenza A (H1N1) pdm09 from 2009 to 2023.

The H1N1pdm09 virus has been a persistent threat to public health since the 2009 pandemic. Particularly, since the relaxation of COVID-19 pandemic mitigation measures, the influenza virus and SARS-CoV-2 have been concurrently prevalent worldwide. To determine the antigenic evolution pattern of H1N1pdm09 and develop preventive countermeasures, we collected influenza sequence data and immunological data to establish a new antigenic evolution analysis framework. A machine learning model (XGBoost, accuracy = 0.86, area under the receiver operating characteristic curve = 0.89) was constructed using epitopes, physicochemical properties, receptor binding sites, and glycosylation sites as features to predict the antigenic similarity relationships between influenza strains. An antigenic correlation network was constructed, and the Markov clustering algorithm was used to identify antigenic clusters. Subsequently, the antigenic evolution pattern of H1N1pdm09 was analyzed at the global and regional scales across three continents. We found that H1N1pdm09 evolved into around five antigenic clusters between 2009 and 2023 and that their antigenic evolution trajectories were characterized by cocirculation of multiple clusters, low-level persistence of former dominant clusters, and local heterogeneity of cluster circulations. Furthermore, compared with the seasonal H1N1 virus, the potential cluster-transition determining sites of H1N1pdm09 were restricted to epitopes Sa and Sb. This study demonstrated the effectiveness of machine learning methods for characterizing antigenic evolution of viruses, developed a specific model to rapidly identify H1N1pdm09 antigenic variants, and elucidated their evolutionary patterns. Our findings may provide valuable support for the implementation of effective surveillance strategies and targeted prevention efforts to mitigate the impact of H1N1pdm09.

Interim 2023/2024 Season Influenza Vaccine Effectiveness in Primary and Secondary Care in the United Kingdom.

BACKGROUND: We report 2023/2024 season interim influenza vaccine effectiveness for three studies, namely, primary care in Great Britain, hospital settings in Scotland and hospital settings in England. METHODS: A test negative design was used to estimate vaccine effectiveness. RESULTS: Estimated vaccine effectiveness against all influenzas ranged from 63% (95% confidence interval 46 to 75%) to 65% (41 to 79%) among children aged 2-17, from 36% (20 to 49%) to 55% (43 to 65%) among adults 18-64 and from 40% (29 to 50%) to 55% (32 to 70%) among adults aged 65 and over. CONCLUSIONS: During a period of co-circulation of influenza A(H1N1)pdm09 and A(H3N2) in the United Kingdom, evidence for effectiveness of the influenza vaccine in both children and adults was found.

Cost-effectiveness of the adjuvanted quadrivalent influenza vaccine for older adults in South Korea.

South Korea's National Immunization Program administers the quadrivalent influenza vaccine (QIV) to manage seasonal influenza, with a particular focus on the elderly. After reviewing the safety and immune response triggered by the adjuvanted QIV (aQIV) in individuals aged 65 and older, the Ministry of Food and Drug Safety in Korea approved its use. However, the extensive impact of aQIV on public health is yet to be fully understood. This study assessed the cost-effectiveness of replacing QIV with aQIV in South Korean adults aged 65 years and older. A dynamic transmission model, calibrated with national influenza data, was applied to compare the influence of aQIV and QIV on older adults and the broader population throughout a single influenza season. This study considered both the direct and indirect effects of vaccination on the elderly. We derived the incremental cost-effectiveness ratios (ICERs) from quality-adjusted life-years (QALYs) and costs incurred, validated through a probabilistic sensitivity analysis with 5,000 simulations. Findings suggest that transitioning to aQIV from QIV in the elderly would be cost-effective, particularly if aQIV's efficacy reaches or exceeds 56.1%. With an ICER of $29,267/QALY, considerably lower than the $34,998/QALY willingness-to-pay threshold, aQIV presents as a cost-effective option. Thus, implementing aQIV with at least 56.1% efficacy is beneficial from both financial and public health perspectives in mitigating seasonal influenza in South Korea.

Assessing the determinants of influenza and COVID-19 vaccine co-administration decisions in the elderly.

This research examines the low rate of co-administration of influenza and COVID-19 vaccines among seniors aged 65 and older in Korea, despite recommendations from authorities and academia worldwide. The study aimed to understand the influence of general characteristics and health beliefs on the vaccination choices of seniors, who were categorized into four groups based on their vaccination status: influenza only, COVID-19 only, both, or neither. A total of 400 participants, aged 65 and above, were selected through proportional stratified random sampling from five major Korean regions for a survey conducted between November 24th and December 15th, 2023. The results indicated no significant differences in general characteristics across these groups. However, regarding the health beliefs showed significant differences in perceived susceptibility and self-efficacy between the influenza-only and co-administration groups. Higher levels of perceived susceptibility and self-efficacy were associated with choosing co-administration. Contrary to previous studies focusing on safety concerns as a primary factor in vaccine hesitancy, this study highlights the role of individual health-related beliefs, particularly perceived susceptibility and self-efficacy, as critical in influencing the decision for co-administration among the elderly in Korea.

Immune memory shapes human polyclonal antibody responses to H2N2 vaccination.

Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase 1 clinical trial investigating a ferritin nanoparticle vaccine displaying H2 hemagglutinin (HA) in H2-naive and H2-exposed adults enabled us to perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited. We temporally map the epitopes targeted by serum antibodies after vaccine prime and boost, revealing that previous H2 exposure results in higher responses to the variable HA head domain. In contrast, initial responses in H2-naive participants are dominated by antibodies targeting conserved epitopes. We use cryoelectron microscopy and monoclonal B cell isolation to describe the molecular details of cross-reactive antibodies targeting conserved epitopes on the HA head, including the receptor-binding site and a new site of vulnerability deemed the medial junction. Our findings accentuate the impact of pre-existing influenza exposure on serum antibody responses post-vaccination.

The antigenic landscape of human influenza N2 neuraminidases from 2009 until 2017.

Human H3N2 influenza viruses are subject to rapid antigenic evolution which translates into frequent updates of the composition of seasonal influenza vaccines. Despite these updates, the effectiveness of influenza vaccines against H3N2-associated disease is suboptimal. Seasonal influenza vaccines primarily induce hemagglutinin-specific antibody responses. However, antibodies directed against influenza neuraminidase (NA) also contribute to protection. Here, we analysed the antigenic diversity of a panel of N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. The antigenic breadth of these NAs was determined based on the NA inhibition (NAI) of a broad panel of ferret and mouse immune sera that were raised by infection and recombinant N2 NA immunisation. This assessment allowed us to distinguish at least four antigenic groups in the N2 NAs derived from human H3N2 viruses that circulated between 2009 and 2017. Computational analysis further revealed that the amino acid residues in N2 NA that have a major impact on susceptibility to NAI by immune sera are in proximity of the catalytic site. Finally, a machine learning method was developed that allowed to accurately predict the impact of mutations that are present in our N2 NA panel on NAI. These findings have important implications for the renewed interest to develop improved influenza vaccines based on the inclusion of a protective NA antigen formulation.

Two proteins, the hemagglutinin and the neuraminidase, protrude from the surface of the influenza virus. Their detection by the immune system allows the host organism to mount defences against the viral threat. The virus evolves in response to this pressure, which manifests as changes in the appearance of its hemagglutinin and neuraminidase. This process, known as antigenic drift, leads to the proteins evading detection. It is also why flu vaccines require frequent updates, as they rely on 'training' the immune system to recognise the most important strains in circulation ­ primarily by exposing it to appropriate versions of hemagglutinin. While the antigenic drift of hemagglutinin has been extensively studied, much less is known about how the neuraminidase accumulates mutations, and how these affect the immune response. To investigate this question, Catani et al. selected 43 genetically distant neuraminidases from human viral samples isolated between 2009 and 2017. Statistical analyses were applied to define their relatedness, revealing that a group of closely related neuraminidases predominated from 2009 to 2015, before they were being taken over by a second group. A third group, which was identified in viruses isolated in 2013, was remarkably close to the neuraminidase of strains that circulated in the late 1990s. The fourth and final group of neuraminidases was derived from influenza viruses that normally circulate in pigs but can also occasionally infect humans. Next, Catani et al. examined the immune response that these 43 neuraminidases could elicit in mice, as well as in ferrets ­ the animal most traditionally used in influenza research. This allowed them to pinpoint which changes in the neuraminidase sequences were important to escape recognition by the host. Data obtained from the two model species were comparable, suggesting that these experiments could be conducted on mice going forward, which are easier to work with than ferrets. Finally, Catani et al. used machine learning to build a computational model that could predict how strongly the immune system would respond to a specific neuraminidase variant. These findings could help guide the development of new vaccines that include neuraminidases tailored to best prime and train the immune system against a larger variety of strains. This may aid the development of 'supra-seasonal' vaccines that protect against a broad range of influenza viruses, reducing the need for yearly updates.

Public health and economic benefits of seasonal influenza vaccination in risk groups in France, Italy, Spain and the UK: state of play and perspectives.

BACKGROUND: Seasonal influenza epidemics have a substantial public health and economic burden, which can be alleviated through vaccination. The World Health Organization (WHO) recommends a 75% vaccination coverage rate (VCR) in: older adults (aged ≥ 65 years), individuals with chronic conditions, pregnant women, children aged 6-24 months and healthcare workers. However, no European country achieves this target in all risk groups. In this study, potential public health and economic benefits achieved by reaching 75% influenza VCR was estimated in risk groups across four European countries: France, Italy, Spain, and the UK. METHODS: A static epidemiological model was used to estimate the averted public health and economic burden of increasing the 2021/2022 season VCR to 75%, using the efficacy data of standard-dose quadrivalent influenza vaccine. For each country and risk group, the most recent data on population size, VCR, pre-pandemic influenza epidemiology, direct medical costs and absenteeism were identified through a systematic literature review, supplemented by manual searching. Outcomes were: averted influenza cases, general practitioner (GP) visits, hospitalisations, case fatalities, number of days of work lost, direct medical costs and absenteeism-related costs. RESULTS: As of the 2021/2022 season, the UK achieved the highest weighted VCR across risk groups (65%), followed by Spain (47%), France (44%) and Italy (44%). Based on modelling, the 2021/2022 VCR prevented an estimated 1.9 million influenza cases, avoiding 375,200 GP visits, 73,200 hospitalisations and 38,400 deaths. To achieve the WHO 75% VCR target, an additional 24 million at-risk individuals would need to be vaccinated, most of which being older adults and patients with chronic conditions. It was estimated that this could avoid a further 918,200 influenza cases, 332,000 GP visits, 16,300 hospitalisations and 6,300 deaths across the four countries, with older adults accounting for 52% of hospitalisations and 80% of deaths. An additional €84 million in direct medical costs and €79 million in absenteeism costs would be saved in total, with most economic benefits delivered in France. CONCLUSIONS: Older adults represent most vaccine-preventable influenza cases and deaths, followed by individuals with chronic conditions. Health authorities should prioritise vaccinating these populations for maximum public health and economic benefits.

Analysis of the epidemiological situation of influenza in Guangzhou under the prevention and control of COVID-19 in June 2022.

OBJECTIVE: Under the prevention and control measures of COVID-19, the epidemiological situation of respiratory pathogens is not well known. Understanding the patterns of respiratory pathogens epidemiology under the prevention and control measures of COVID-19 is important to guide resource allocation for existing and future treatment and prevention strategies. METHODS: In total, 659 fever outpatients nasopharyngeal swabs were collected at fever illness onset during June in 2022 at the First Hospital of Guangzhou Medical University. Swabs were tested by real-time fluorescent single-tube multiplex polymerase chain reaction (PCR) for 12 respiratory pathogens. Moreover, 108 of the 659 swabs were tested for influenza virus antigen. RESULTS: At least one pathogen was detected in 477 (72.38%) of 659 fever outpatients with multiple pathogens identified in 25 (3.79%). The highest multiple infectious pattern is parainfluenza virus in combination with influenza (five cases). Influenza A virus (IFA), human rhinovirus (HRV), and parainfluenza virus are the three leading virus pathogens with proportions of 64.64%, 5.01%, and 2.88%. School-age children and adult groups have the highest pathogens positivity rate of 81.28% and 83.87%. CONCLUSION: A high proportion of adolescents and adults has respiratory pathogens detected during fever illnesses during June in 2022 under the prevention and control of COVID-19. These data indicate that diagnosis, prevention, and control of respiratory tract infection should be paid attention under the prevention and control of COVID-19.

Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza among Chinese elderly: a test-negative design.

BACKGROUND: Evidence on the effectiveness of influenza vaccination in the elderly is limited, and results are controversial. There are also few reports from China. METHODS: We conducted a test-negative case-control study design to estimate influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated visits among elderly (aged ≥ 60 years) across four influenza seasons in Ningbo, China, from 2018 to 19 to 2021-22. Influenza-positive cases and negative controls were randomly matched in a 1:1 ratio according to age, sex, hospital, and date of influenza testing. We used logistic regression models to compare vaccination odds ratios (ORs) in cases to controls. We calculated the VE as [100% × (1-adjusted OR)] and calculated the 95% confidence interval (CI) around the estimate. RESULTS: A total of 30,630 elderly patients tested for influenza with virus nucleic acid or antigen during the study period. After exclusions, we included 1 825 influenza-positive cases and 1 825 influenza-negative controls. Overall, the adjusted VE for influenza-related visits was 63.5% (95% CI, 56.3-69.5%), but varied by season. Influenza VE was 59.8% (95% CI, 51.5-66.7%) for influenza A and 89.6% (95% CI, 77.1-95.3%) for influenza B. The VE for ages 60-69 and 70-79 was 65.2% (95% CI, 55.4-72.9%) and 69.8% (95% CI, 58.7-77.9%), respectively, but only 45.4% (95% CI, 6.2-68.2%) for ages 80 and over. CONCLUSIONS: Standard-dose inactivated influenza vaccine has shown good protection in the elderly in China. However, protection may not be satisfactory in people aged 80 years and older.

Consensus statements for influenza awareness, prevention, and vaccination in Pakistan.

INTRODUCTION: Influenza is a serious underestimated viral infection in Pakistan and influenza vaccination and vaccination awareness are low. The current work aimed to develop consensus on influenza epidemiology, prevention, vaccination, and awareness in Pakistan. METHODOLOGY: A systematic literature search was conducted to develop recommendations on influenza vaccines in Pakistan. Experts' feedback was incorporated using the modified Delphi method. A three-step process was used, with 18 experts from different specialties from Pakistan who participated in voting rounds to achieve a minimum 75% agreement level. RESULTS: Pakistan has a low-immunization-rate and is susceptible to serious influenza outbreaks and influenza-related complications. Influenza circulates year-round in Pakistan but peaks during January and February. The subtype A/H1N1 is predominant. The experts urged vaccination in all individuals ≥ 6 months of age and with no contraindications. They highlighted special considerations for those with comorbidities and specific conditions. The experts agreed that the inactivated influenza vaccine is safe and efficient in pregnant women, immunocompromised, and comorbid respiratory and cardiovascular patients. Finally, the experts recommended conducting promotional and educational programs to raise awareness on influenza and vaccination. CONCLUSIONS: This is the first regional consensus on influenza and influenza vaccination in Pakistan with experts' recommendations to increase influenza vaccination and decrease influenza cases and its associated detrimental effects.

Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response.

Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. Vaccination is generally accepted as the most effective strategy for influenza prevention. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidate, evaluate its immunogenicity using the hemagglutination inhibition assay, ELISA, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidate compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.

Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.

Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be updated and readministered annually. To increase the breadth of influenza vaccine-mediated protection, we developed an antigenically complex mixture of recombinant HAs designed to redirect immune responses to more conserved domains of the protein. Vaccine-induced antibodies were disproportionally redistributed to the more conserved stalk of the HA without hindering, and in some cases improving, antibody responses against the head domain. These improved responses led to increased protection against homologous and heterologous viral challenges in both mice and ferrets compared with conventional vaccine approaches. Thus, antigenically complex protein mixtures can at least partially overcome HA head domain antigenic immunodominance and may represent a step toward a more universal influenza vaccine.

Enhancing vaccination uptake through community engagement: evidence from China.

With growing recognition of the importance of community engagement in addressing public health challenges, its role in promoting healthy behaviors and preventing infectious diseases has gained attention. However, vaccination coverage remains a significant concern in many developing countries. While previous studies have linked community engagement to positive health outcomes, there is a gap in understanding its influence on individual vaccination choices, particularly in the context of developing countries. Utilizing data from the 2021 Chinese General Social Survey (CGSS), this study examines the impact of community engagement on COVID-19 and flu vaccination uptake among 7281 individuals. Community engagement, measured by community vaccination notifications, serves as the key independent variable. The study employs Ordinary Least Squares (OLS) regression and Propensity Score Matching (PSM) methods to analyze the relationship between community engagement and vaccination behavior. The analysis reveals a positive association between community engagement and vaccination rates. Specifically, individuals receiving notifications were more likely to get the COVID-19 vaccine compared to non-recipients (vaccination rates: 100% vs. 53.3%), and flu vaccination rates were also significantly higher among those notified (2.7% vs. 1.9%). Mechanism analysis suggests that individuals receiving community notifications are more aware of the benefits of vaccination, leading to higher vaccination rates among this group. This study underscores the effectiveness of community engagement strategies in promoting positive vaccination behavior among individuals in China. By enhancing awareness and trust in immunization, community engagement initiatives play a crucial role in shaping health behaviors and improving vaccination uptake. These findings emphasize the importance of integrating community engagement approaches into public health interventions to address vaccination challenges.

Understanding the gap between guidelines and influenza vaccination coverage in people with diabetes: a scoping review.

Background: Diabetes affects millions of people worldwide, making them more vulnerable to infections, including seasonal influenza. It is therefore particularly important for those suffering from diabetes to be vaccinated against influenza each year. However, influenza vaccination coverage remains low in this population. This review primarily aims to identify the determinants of influenza vaccination in people with diabetes (T1D or T2D). Secondly, it aims to assess main recommendations for influenza vaccination, vaccine effectiveness, vaccination coverage, and how education and pharmacists can encourage uptake of the vaccine in the diabetic population. Methods: A scoping review was conducted in January 2022 to systematically review evidence on influenza vaccination in people with diabetes using data from PubMed, Science Direct, and EM Premium with terms such as "Diabetes mellitus," "Immunization Programs," "Vaccination," and "Influenza Vaccines." Quality assessment and data extraction were independently conducted by two authors. Disagreements between the authors were resolved through discussion and consensus, and if necessary, by consulting a third author. Results: Of the 333 records identified, 55 studies met the eligibility criteria for inclusion in this review. Influenza vaccination was recommended for people ≥6 months. Despite effectiveness evidence showing a reduction in mortality and hospitalizations in people with diabetes vaccinated vs. non-vaccinated ones, very few studies reported a coverage rate ≥ 75%, which is WHO's target objective. Determinants such as advanced age, presence of comorbidities and healthcare givers' advice were associated with increased vaccination uptake. On the contrary, fear of adverse reactions and concerns about vaccine effectiveness were significant barriers. Finally, education and pharmacists' intervention played a key role in promoting vaccination and increasing vaccination uptake. Conclusion: Influenza vaccination coverage in people with diabetes remains low despite recommendations and evidence on vaccine effectiveness. Motivators and barriers as well as several socio-demographic and clinical factors have been identified to explain this trend. Efforts are now needed to increase the number of diabetics vaccinated against influenza, mainly through education and the involvement of healthcare givers.

Association between combination COVID-19-influenza vaccination and long COVID in middle-aged and older Europeans: A cross-sectional study.

The potential impact of combined COVID-19 and influenza vaccination on long COVID remains uncertain. In the present cross-sectional study, we aimed to investigate the plausible association between them in middle-aged and older Europeans based on the Survey of Health, Ageing, and Retirement in Europe (SHARE). A total of 1910 participants were recruited in the analyses. The study outcome was long COVID. Participants were divided into 4 groups through the self-reported status of COVID-19 and influenza vaccination. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. 1397 participants experienced long COVID. After multivariable adjustment, those vaccinated with neither COVID-19 nor influenza vaccine had higher risk of long COVID (OR, 1.72; 95% CI, 1.26-2.35) compared to those vaccinated with both vaccines. Furthermore, adding the 4 statuses of COVID-19 vaccination/influenza vaccination to conventional risk model improved risk reclassification for long COVID (continuous net reclassification improvement was 16.26% [p = .003], and integrated discrimination improvement was 0.51% [p = .005]). No heterogeneity was found in the subgroup analyses (all p-interaction ≥0.05). Our study might provide a strategy for people aged 50 and over to reduce the occurrence of long COVID, that is, to combine the use of the COVID-19 vaccine and influenza vaccines.

Evaluating the impact of school-based influenza vaccination programme on absenteeism and outbreaks at schools in Hong Kong: a retrospective cohort study protocol.

INTRODUCTION: Seasonal influenza causes annual school breaks and student absenteeism in Hong Kong schools and kindergartens. This proposal aims to conduct a retrospective cohort study to evaluate the impact of a school-based influenza vaccination (SIV) programme on absenteeism and outbreaks at schools in Hong Kong. METHODS: The study will compare schools that implemented the SIV programme with schools that did not. The data will be sourced from school records, encompassing absenteeism records, outbreak reports, and vaccination rates. We will recruit 1000 students from 381 schools and kindergartens in 18 districts of Hong Kong starting June 2024. The primary outcome measures will include absenteeism rates due to influenza and school influenza outbreaks. Secondary outcomes will consist of vaccination coverage rates and the impact of the SIV programme on hospitalisations due to influenza-like illness. A t-test will be conducted to compare the outcomes between schools with and without the SIV programme. ETHICS AND DISSEMINATION: The school completed signing the participants' informed consent form before reporting the data to us. Our study has been approved by the Hospital Authority Hong Kong West Cluster IRB Committee (IRB No: UW 17-111) and was a subtopic of the research "The estimated age-group specific influenza vaccine coverage rates in Hong Kong and the impact of the school outreach vaccination program". TRIAL REGISTRATION: This study will be retrospectively registered.

Quadrivalent Live-Attenuated Influenza Vaccine in Milan preschools: an Italian experience of school-located flu vaccination within the 2022-2023 season.

BACKGROUND: In Italy, since the 2020-2021 flu season, the flu vaccine recommendation was extended to all children aged 6 months to 6 years and quadrivalent Live-Attenuated Influenza Vaccine (qLAIV) was introduced. Since school-aged children are important carriers of annual influenza epidemics, a school-based influenza vaccination program may potentially increase vaccine uptake. Recent studies, conducted in the UK and the US, show that school-based vaccination can reach higher percentage of paediatric vaccination coverage compared to children vaccinated in other settings. METHODS: During 2022-2023 flu season in 9 preschools located in Milan healthcare personnel vaccinated children with qLAIV at the end of a school day. A Google Form questionnaire was administered to preschoolers' parents of all preschools within the Municipality of Milan. RESULTS: In the preschools engaged in the vaccination program, 233 out of 1939 children were vaccinated (12%). Among these, 61 (26.2%) had never been vaccinated for influenza before. Vaccination coverage was 11.5% for Italian children and 14.3% for children coming from an immigrant background. We collected 3659 questionnaire responses, divided according to study participation status (371 from preschools that participated in the vaccination program and 3288 from other preschools in Milan). 57% of the families who answered to the questionnaire vaccinated their children for flu. qLAIV accounted for 85.6% of vaccinations. We observed a statistically significant difference in the percentage of vaccinated children between those attending a school participating in the project (67.9%) and children attending other schools (56%) (p < 0.001). Vaccination was administered by family pediatricians (48.9%), in vaccination centers (34.8%), in vaccine hubs (11.3%), in schools (2.6%), by private pediatricians (1.6%) and in other settings (0.7%). Focusing on the responses from families whose children attend schools participating in the vaccination program, 21.8% stated that the vaccination was provided in school. CONCLUSION: According to our experience, in Italy, at the moment, only the cooperation between health providers and alternative settings, including schools, may expand flu vaccination coverage. In particular, schools are to be considered a place to inform and reach out to families, useful to increase vaccination coverage.

Immunity by AS03ation: The natural adjuvantage.

Humans do not respond equally to vaccination. To investigate why, Mulè et al. developed a multimodal framework and found that high responders after unadjuvanted influenza vaccination exist in a naturally adjuvanted state, mimicking innate immunophenotypes following AS03-adjuvanted vaccination. This highlights biological factors that set apart high-antibody responders and how adjuvants can boost innate immune cues to improve humoral immunity.

The effect of oral probiotics on response to vaccination in older adults: a systematic review of randomised controlled trials.

This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this.