Seasonal Vaccine Research Articles

Parent and family characteristics associated with reported pediatric influenza vaccination in a sample of Canadian digital vaccination platform users. An exploratory, cross-sectional study in the 2018-2019 influenza season

ABSTRACT Seasonal vaccination remains one of the best interventions to prevent morbidity and mortality from influenza in children. Understanding the characteristics of parents who vaccinate their children can inform communication strategies to encourage immunization. Using a cross-sectional study, we described parental characteristics of people who reported vaccinating their children against influenza during 2018/2019 in a cohort of Canadian digital immunization record users. Data was collected from a free, Pan-Canadian digital vaccination tool, CANImmunize. Eligible accounts contained at least one parental and one “child/dependent” record. Each parental characteristic (gender, age, family size, etc) was tested for association with pediatric influenza vaccination, and a multivariate logistic regression model was fit. A total of 6,801 CANImmunize accounts met inclusion criteria. After collapsing the dataset, the final sample contained 11,381 unique dyads. Influenza vaccination was reported for 32.3% of the children and 42.0% of the parents. In the multivariate logistic regression analysis, parents receiving the seasonal influenza vaccine were most strongly associated with reporting pediatric influenza vaccination (OR 17.05, 95% CI 15.08, 19.28). Having a larger family size and fewer transactions during the study period was associated with not reporting pediatric influenza vaccination. While there are several limitations to this large-scale study, these results can help inform future research in the area. Digital technologies may provide a unique and valuable source of vaccine coverage data and to explore associations between individual characteristics and immunization behavior. Policy makers considering digital messaging may want to tailor their efforts based on parental characteristics to further improve pediatric seasonal influenza vaccine uptake.

Structural Mapping of Polyclonal IgG Responses to HA After Influenza Virus Vaccination or Infection.

Cellular and molecular characterization of immune responses elicited by influenza virus infection and seasonal vaccination have informed efforts to improve vaccine efficacy, breadth, and longevity. Here, we use negative stain electron microscopy polyclonal epitope mapping (nsEMPEM) to structurally characterize the humoral IgG antibody responses to hemagglutinin (HA) from human patients vaccinated with a seasonal quadrivalent flu vaccine or infected with influenza A viruses. Our data show that both vaccinated and infected patients had humoral IgGs targeting highly conserved regions on both H1 and H3 subtype HAs, including the stem and anchor, which are targets for universal influenza vaccine design. Responses against H1 predominantly targeted the central stem epitope in infected patients and vaccinated donors, whereas head epitopes were more prominently targeted on H3. Responses against H3 were less abundant, but a greater diversity of H3 epitopes were targeted relative to H1. While our analysis is limited by sample size, on average, vaccinated donors responded to a greater diversity of epitopes on both H1 and H3 than infected patients. These data establish a baseline for assessing polyclonal antibody responses in vaccination and infection, providing context for future vaccine trials and emphasizing the importance of carefully designing vaccines to boost protective responses towards conserved epitopes.

Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal Outcomes

A nonadjuvanted bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF [Pfizer]) protein subunit vaccine was newly approved and recommended for pregnant individuals at 32 0/7 to 36 6/7 weeks' gestation during the 2023 to 2024 RSV season; however, clinical vaccine data are lacking. To evaluate the association between prenatal RSV vaccination status and perinatal outcomes among patients who delivered during the vaccination season. This retrospective observational cohort study was conducted at 2 New York City hospitals within 1 health care system among patients who gave birth to singleton gestations at 32 weeks' gestation or later from September 22, 2023, to January 31, 2024. Prenatal RSV vaccination with the RSVpreF vaccine captured from the health system's electronic health records. The primary outcome is preterm birth (PTB), defined as less than 37 weeks' gestation. Secondary outcomes included hypertensive disorders of pregnancy (HDP), stillbirth, small-for-gestational age birth weight, neonatal intensive care unit (NICU) admission, neonatal respiratory distress with NICU admission, neonatal jaundice or hyperbilirubinemia, neonatal hypoglycemia, and neonatal sepsis. Logistic regression models were used to estimate odds ratios (ORs), and multivariable logistic regression models and time-dependent covariate Cox regression models were performed. Of 2973 pregnant individuals (median [IQR] age, 34.9 [32.4-37.7] years), 1026 (34.5%) received prenatal RSVpreF vaccination. Fifteen patients inappropriately received the vaccine at 37 weeks' gestation or later and were included in the nonvaccinated group. During the study period, 60 patients who had evidence of prenatal vaccination (5.9%) experienced PTB vs 131 of those who did not (6.7%). Prenatal vaccination was not associated with an increased risk for PTB after adjusting for potential confounders (adjusted OR, 0.87; 95% CI, 0.62-1.20) and addressing immortal time bias (hazard ratio [HR], 0.93; 95% CI, 0.64-1.34). There were no significant differences in pregnancy and neonatal outcomes based on vaccination status in the logistic regression models, but an increased risk of HDP in the time-dependent model was seen (HR, 1.43; 95% CI, 1.16-1.77). In this cohort study of pregnant individuals who delivered at 32 weeks' gestation or later, the RSVpreF vaccine was not associated with an increased risk of PTB and perinatal outcomes. These data support the safety of prenatal RSVpreF vaccination, but further investigation into the risk of HDP is warranted.

MRI in LARS1 deficiency-Spectrum, patterns, and correlation with acute neurological deterioration.

Leucine aminoacyl tRNA-synthetase 1 (LARS1)-deficiency (infantile liver failure syndrome type 1 (ILFS1)) has a multisystemic phenotype including fever-associated acute liver failure (ALF), chronic neurologic abnormalities, and encephalopathic episodes. In order to better characterize encephalopathic episodes and MRI changes, 35 cranial MRIs from 13 individuals with LARS1 deficiency were systematically assessed and neurological phenotype was analyzed. All individuals had developmental delay and 10/13 had seizures. Encephalopathic episodes in 8/13 were typically associated with infections, presented with seizures and reduced consciousness, mostly accompanied by hepatic dysfunction, and recovery in 17/19 episodes. Encephalopathy without hepatic dysfunction occurred in one individual after liver transplantation. On MRI, 5/7 individuals with MRI during acute encephalopathy had deep gray matter and brainstem changes. Supratentorial cortex involvement (6/13) and cerebellar watershed injury (4/13) occurred with seizures and/or encephalopathy. Abnormal brainstem contour on sagittal images (8/13), atrophy (8/13), and myelination delay (8/13) were not clearly associated with encephalopathy. The pattern of deep gray matter and brainstem changes are apparently characteristic of encephalopathy in LARS1-deficiency, differing from patterns of hepatic encephalopathy or metabolic stroke in organic acidurias and mitochondrial diseases. While the pathomechanism remains unclear, fever and energy deficit during infections might be causative; thus, sufficient glucose and protein intake along with pro-active fever management is suggested. As severe episodes were observed during influenza infections, we strongly recommend seasonal vaccination.

Neutralizing antibody responses against contemporary and future influenza A(H3N2) viruses in paradoxical clades elicited by repeated and single vaccinations.

As one of the most effective measures to prevent seasonal influenza viruses, annual influenza vaccination is globally recommended. Nevertheless, evidence regarding the impact of repeated vaccination to contemporary and future influenza has been inconclusive. A total of 100 subjects singly or repeatedly immunized with influenza vaccines including 3C.2a1 or 3C.3a1 A(H3N2) during 2018-2019 and 2019-2020 influenza season were recruited. We investigated neutralization antibody by microneutralization assay using four antigenically distinct A(H3N2) viruses circulating from 2018 to 2023, and tracked the dynamics of B cell receptor (BCR) repertoire for consecutive vaccinations. We found that vaccination elicited cross-reactive antibody responses against future emerging strains. Broader neutralizing antibodies to A(H3N2) viruses and more diverse BCR repertoires were observed in the repeated vaccination. Meanwhile, a higher frequency of BCR sequences shared among the repeated-vaccinated individuals with consistently boosting antibody response was found than those with a reduced antibody response. Our findings suggest that repeated seasonal vaccination could broaden the breadth of antibody responses, which may improve vaccine protection against future emerging viruses.

Effectiveness against severe COVID-19 of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines in persons aged ≥60 years: Estimates over calendar time and by time since administration during prevalent circulation of different Omicron subvariants, Italy, 2022–2023

Evaluating how a COVID-19 seasonal vaccination program performed might help to plan future campaigns. This study aims to estimate the relative effectiveness (rVE) against severe COVID-19 of a seasonal booster dose over calendar time and by time since administration.We conducted a retrospective cohort analysis among 13,083,855 persons aged ≥60 years who were eligible to receive a seasonal booster at the start of the 2022–2023 vaccination campaign in Italy. We estimated rVE against severe COVID-19 (hospitalization or death) of a seasonal booster dose of bivalent (original/Omicron BA.4-5) mRNA vaccines by two-month calendar interval and at different times post-administration. We used multivariable Cox regression models, including vaccination as time-dependent exposure, to estimate adjusted hazard ratios (HR) and rVEs as [(1-HR)X100].The rVE of a seasonal booster decreased from 64.9% (95% CI: 59.8–69.4) in October-November 2022 to 22.0% (95% CI: 15.4–28.0) in April-May 2023, when the majority of vaccinated persons (67%) had received the booster at least 4–6 months earlier. During the epidemic phase with prevalent circulation of the Omicron BA.5 subvariant, rVE of a seasonal booster received ≤90 days earlier was 83.0% (95% CI: 79.1–86.1), compared to 37.4% (95% CI: 25.5–47.5) during prevalent circulation of the Omicron XBB subvariant. During the XBB epidemic phase, rVE was estimated at 15.8% (95% CI: 9.1–20.1) 181–369 days post-administration of the booster dose. In all the analyses we observed similar trends of rVE between persons aged 60–79 and those ≥80 years, although estimates were somewhat lower for the oldest group.A seasonal booster dose received during the vaccination campaign provided additional protection against severe COVID-19 up to April-May 2023, after which the incidence of severe COVID-19 was much reduced. The results also suggest that the Omicron XBB subvariant might have partly escaped the immunity provided by the seasonal booster targeting the original and Omicron BA.4-5 strains of SARS-CoV-2.

Isolation of human antibodies against influenza B neuraminidase and mechanisms of protection at the airway interface

Influenza B viruses (IBVs) comprise a substantial portion of the circulating seasonal human influenza viruses. Here, we describe the isolation of human monoclonal antibodies (mAbs) that recognized the IBV neuraminidase (NA) glycoprotein from an individual following seasonal vaccination. Competition-binding experiments suggested the antibodies recognized two major antigenic sites. One group, which included mAb FluB-393, broadly inhibited IBV NA sialidase activity, protected prophylactically invivo, and bound to the lateral corner of NA. The second group contained an active site mAb, FluB-400, that broadly inhibited IBV NA sialidase activity and virus replication invitro in primary human respiratory epithelial cell cultures and protected against IBV invivo when administered systemically or intranasally. Overall, the findings described here shape our mechanistic understanding of the human immune response to the IBV NA glycoprotein through the demonstration of two mAb delivery routes for protection against IBV and the identification of potential IBV therapeutic candidates.

Analysing the Potency of a Seasonal Influenza Vaccine Using Reference Antisera from Heterologous Strains.

The potency of inactivated seasonal influenza vaccine is harmonised by establishing the haemagglutinin (HA) content using the compendial single radial diffusion (SRD) method. SRD reagents (antigens and antisera) are prepared, calibrated and distributed by regulatory agencies as standards for potency testing, following the biannual World Health Organization (WHO) announcements of the virus strains suitable for inclusion in the vaccine. The generation of a homologous hyperimmune sheep antiserum constrains the time to vaccine release. This study tests the application of heterologous antisera to determine the potency of influenza vaccine compared to that of a standard homologous antiserum. The results indicate that the selected heterologous sheep antisera directed to seasonal H1N1, H3N2 or B Victoria virus strains can be used to determine the accurate potency of inactivated seasonal influenza vaccines. Individually selected antisera could be useful for two to fourteen seasons. A limitation to the heterologous antiserum approach is the diversity of each individual serum, indicating that the empirical determination of a specific serum is required. This application has the potential to enable the earlier availability of a seasonal vaccine and reduce animal usage.

Hemagglutinin stalk-specific Fc-mediated functions are associated with protection against influenza-illness after seasonal influenza vaccination in pregnant women.

Several influenza vaccine candidates aim to elicit antibodies against the conserved hemagglutinin stalk domain. Understanding the protective mechanism of these antibodies, which mediate broad neutralization and Fc-mediated functions, following seasonal vaccination is critical. Plasma samples were obtained from a subset of pregnant women living with or without HIV-1 enrolled in a randomised trial (138 trivalent inactivated vaccine [TIV] and 145 placebo recipients). Twenty-three influenza-illness cases were confirmed within 6 months postpartum. We measured H1 stalk-specific antibody-dependent cellular phagocytosis (ADCP), complement deposition (ADCD) and cellular cytotoxicity (ADCC) at enrolment and 1-month post-vaccination. The association between these Fc-mediated functions and protection against influenza-illness following vaccination was examined using multiple logistic regression analysis and risk reduction thresholds were defined by the score associated with the lowest odds of influenza-illness. Amongst TIV and placebo recipients, lower H1 stalk-specific ADCP and ADCD activity was detected for participants with confirmed influenza compared with individuals without confirmed influenza-illness 1-month post-vaccination. Pre-existing ADCP scores ≥250 reduced the odds of A/H1N1 infection (odds ratio 0.11; p=0.01) with an 83% likelihood of risk reduction. Following TIV, ADCD scores of ≥25 and ≥15 significantly reduced the odds against A/H1N1 (0.10; p=0.01) and non-group 1 (0.06; p=0.0004) influenza virus infections, respectively. These ADCD scores were associated with >84% likelihood of risk reduction. H1 stalk-specific ADCC potential was not associated with protection against influenza-illness. H1 stalk-specific ADCD correlates with protection against influenza-illness following influenza vaccination during pregnancy. These findings provide insight into the protective mechanisms of HA stalk antibodies.

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.

Structural basis for the broad antigenicity of the computationally optimized influenza hemagglutinin X6

Influenza causes significant morbidity and mortality. As an alternative approach to current seasonal vaccines, the computationally optimized broadly reactive antigen (COBRA) platform has been previously applied to hemagglutinin (HA). This approach integrates wild-type HA sequences into a single immunogen to expand the breadth of accessible antibody epitopes. Adding to previous studies of H1, H3, and H5 COBRA HAs, we define the structural features of another H1 subtype COBRA, X6, that incorporates HA sequences from before and after the 2009 H1N1 influenza pandemic. We determined structures of this antigen alone and in complex with COBRA-specific as well as broadly reactive and functional antibodies, analyzing its antigenicity. We found that X6 possesses features representing both historic and recent H1 HA strains, enabling binding to both head- and stem-reactive antibodies. Overall, these data confirm the integrity of broadly reactive antibody epitopes of X6 and contribute to design efforts for a next-generation vaccine.

Safety and effectiveness of single- versus double-dose of seasonal influenza vaccine in kidney transplant recipients: a randomized clinical trial

Introduction. Influenza virus poses significant risks to immunocompromised individuals such as those who have received organ transplants and are undergoing immunosuppressive treatment to prevent transplant rejection. Therefore, annual influenza vaccination is recommended for these individuals. This study aimed to comparison of safety and effectiveness of single- versus double-dose of seasonal influenza vaccine in kidney transplant recipients. Materials and methods. This randomized clinical trial involved 50 kidney transplant recipients at Imam Khomeini Hospital. Participants were randomly assigned to two groups: those receiving a single dose (standard dose) and those receiving a double dose of the seasonal flu vaccine. Serum samples were collected before and 4 weeks after vaccination to measure influenza AB-related antibodies. Sixteen patients were excluded from the study. The trial focused on evaluating the vaccine safety and immunogenicity, as well as documenting any local and systemic side effects following vaccination. Results. The results indicated no significant difference in gender, age, and type of immunosuppressive drug used between the single- and double-dose groups (p 0.05). No significant difference in post-vaccination adverse effects, such as injection site pain (p = 0.21) between the two groups. The seroconversion rates (change from IgG 9 IU/µL to IgG 11 IU/µL) for IgG Influenza A were 12.5% (n = 2) in the single-dose group and 26.7% (n = 4) in the double-dose group, and for IgG Influenza B, they were 11.8% (n = 2) and 21.4% (n = 3), respectively. Conclusion. A double dose of the influenza vaccine slightly enhanced the immune response in kidney transplant patients without causing any adverse side effects.

Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children

Cross-reactive antibodies with Fc receptor (FcR) effector functions may mitigate pandemic virus impact in the absence of neutralizing antibodies. In this exploratory study, we use serum from a randomized placebo-controlled trial of seasonal trivalent influenza vaccination in children (NCT00792051) conducted at the onset of the 2009 H1N1 pandemic (pH1N1) and monitored for infection. We found that seasonal vaccination increases pH1N1 specific antibodies and FcR effector functions. Furthermore, prospective baseline antibody profiles after seasonal vaccination, prior to pH1N1 infection, show that unvaccinated uninfected children have elevated ADCC effector function, FcγR3a and FcγR2a binding antibodies to multiple pH1N1 proteins, past seasonal and avian (H5, H7 and H9) strains. Whereas, children that became pH1N1 infected after seasonal vaccination have antibodies focussed to seasonal strains without FcR functions, and greater aggregated HA-specific profiles for IgM and IgG3. Modeling to predict infection susceptibility, ranked baseline hemagglutination antibody inhibition as the highest contributor to lack of pH1N1 infection, in combination with features that include pH1-IgG1, H1-stem responses and FcR binding to seasonal vaccine and pH1 proteins. Thus, seasonal vaccination can have benefits against pandemic influenza viruses, and some children already have broadly reactive antibodies with Fc potential without vaccination and may be considered ‘elite influenza controllers’.

Supplementation of seasonal vaccine with multi-subtype neuraminidase and M2 ectodomain virus-like particle improves protection against homologous and heterologous influenza viruses in aged mice

The conventional inactivated split seasonal influenza vaccine offers low efficacy, particularly in the elderly and against antigenic variants. Here, to improve the efficacy of seasonal vaccination for the elderly population, we tested whether supplementing seasonal bivalent (H1N1 + H3N2) split (S) vaccine with M2 ectodomain repeat and multi-subtype consensus neuraminidase (NA) proteins (N1 NA + N2 NA + flu B NA) on a virus-like particle (NA-M2e) would induce enhanced cross-protection against different influenza viruses in aged mice. Immunization with split vaccine plus NA-M2e (S + NA-M2e) increased vaccine-specific IgG antibodies towards T-helper type 1 responses and hemagglutination inhibition titers. Aged mice with NA-M2e supplemented vaccination were protected against homologous and heterologous viruses at higher efficacies, as evidenced by preventing weight loss, lowering lung viral loads, inducing broadly cross-protective humoral immunity, and IFN-γ+ CD4 and CD8 T cell responses than those with seasonal vaccine. Overall, this study supports a new strategy of NA-M2e supplemented vaccination to enhance protection against homologous and antigenically different viruses in the elderly.

Real-time investigation of an influenza A(H3N2) virus outbreak in a refugee community, November 2022

ObjectivesTo report epidemiological and virological results of an outbreak investigation of influenza-like illness (ILI) among refugees in Northern Italy. Study designOutbreak investigation of ILI cases observed among nearly 100 refugees in Northern Italy unvaccinated for influenza. MethodsAn epidemiological investigation matched with a differential diagnosis was carried out for each sample collected from ILI cases to identify 10 viral pathogens (SARS-CoV-2, influenza virus type A and B, respiratory syncytial virus, metapneumovirus, parainfluenza viruses, rhinovirus, enterovirus, parechovirus, and adenovirus) by using specific real-time PCR assays according to the Centers for Disease Control and Prevention (CDC) protocols. In cases where the influenza virus type was identified, complete hemagglutinin (HA) gene sequencing and the related phylogenetic analysis were conducted. ResultsThe outbreak was caused by influenza A(H3N2): the attack rate was 83.3% in children aged 9–14 years, 84.6% in those aged 15–24 years, and 28.6% in adults ≥25 years. Phylogenetic analyses uncovered that A(H3N2) strains were closely related since they segregated in the same cluster, showing both a high mean nucleotide identity (100%), all belonging to the genetic sub-group 3C.2a1b.2a.2, as those mainly circulating into the general population in the same period. ConclusionsThe fact that influenza outbreak strains as well as the community strains were genetically related to the seasonal vaccine strain suggests that if an influenza prevention by vaccination strategy had been implemented, a lower attack rate of A(H3N2) and ILI cases might have been achieved.

Promotion of Influenza Vaccination in the Emergency Department

BackgroundInfluenza vaccine uptake is low among underserved populations whose primary health care access occurs in emergency departments. We sought to determine whether implementation of two interventions would increase 30-day influenza vaccine uptake in unvaccinated patients in the emergency department.MethodsThis three-group, prospective, cluster-randomized controlled trial compared two interventions with a control group in noncritically ill, adult patients in the emergency department who were not vaccinated for influenza in the current vaccine season. The unit of randomization was individual calendar days. Participants received either Intervention M (an influenza vaccine messaging platform consisting of a video, one-page flyer, and scripted message, followed by a vaccine acceptance question and provider notification if participants indicated vaccine acceptance), Intervention Q (no messaging but the vaccine acceptance question and provider notification), or control (usual care/no intervention). The primary outcome was receipt of an influenza vaccine at 30 days ascertained by electronic health record review and telephone follow-up, comparing the Intervention M group with the control group. Secondary outcomes included comparisons of 30-day vaccine uptake in Intervention Q versus control and Intervention M versus Intervention Q.ResultsBetween October 2022 and February 2023, a total of 767 trial participants were enrolled at six emergency departments in five U.S. cities. Median age was 46 years; 353 (46%) participants were female, 274 (36%) were African American, and 158 (21%) were Latinx; 126 (16%) lacked health insurance, and 244 (32%) lacked primary care. The Intervention M, Intervention Q, and control groups had 30-day vaccine uptakes of 41%, 32%, and 15%, respectively (P<0.0001 for Intervention M vs. control). Comparing Intervention M versus Intervention Q, the adjusted difference in 30-day vaccine uptake was 8.7 percentage points (95% confidence interval, −0.1 to 17.6 percentage points).ConclusionsImplementation of influenza vaccine messaging platforms (video clips, printed materials, and verbal scripts) improved 30-day vaccine uptake among unvaccinated patients in the emergency department. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05836818.)

Leveraging seasonal influenza health worker vaccination programmes for COVID-19 vaccine Introduction: A global qualitative analysis

BackgroundHealth worker vaccination programmes can help to safeguard both health workers (HWs) and their patients and enhance vaccine uptake more broadly in local communities and society. This study’s objective was to increase global understanding of how existing HW vaccination programmes were leveraged for emergency COVID-19 vaccine introduction. MethodsThis qualitative study included 13 in-depth group interviews with 38 key informants with expertise in vaccine programme implementation from eleven countries in five WHO regions: Albania, Armenia, Bhutan, Lao PDR, Maldives, Mongolia, Oman, Timor Leste, the United Kingdom, Vietnam, and Zimbabwe in addition to WHO regional focal points from all six regions. These interviews were transcribed, coded, and thematically analyzed. Key informants reviewed the initial results and validated the key findings. ResultsInformants characterized key components of both routine and seasonal influenza vaccination programmes that were leveraged for the emergency vaccination of HWs during the COVID-19 pandemic. We identified a set of cross-cutting factors that were used for COVID-19 vaccine roll out: 1) pre-existing occupational health policies, 2) adequate human resources, 3) well-functioning data information systems and vaccine delivery platforms, and 4) established communication channels. Across the eleven countries and six regions interviewed, the ability to adapt existing influenza or other health worker vaccination infrastructure was beneficial for their pandemic response. ConclusionsOur findings suggest a strong justification for enhanced investment in vaccination of health workers, particularly against seasonal influenza, through country-wide programmes as a foundation for pandemic preparedness and response.

Real-life experience on COVID-19 and seasonal influenza vaccines co-administration in the vaccination hub of the University Hospital of Palermo, Italy

ABSTRACT With the pandemic, there has been a global reduction in influenza virus circulation, with WHO reporting, during 2021/22 season, laboratory testing positivity rate for influenza of less than 3%. Influenza surveillance systems anticipated a peak of influenza cases in the Northern Hemisphere during 2022/2023 season and the Italian Ministry of Health recommended the routinary co-administration of influenza with bivalent COVID-19 vaccines for the 2022/2023 season. At the Vaccination Hub of the University Hospital (UH) of Palermo, more than 700 subjects received influenza and COVID-19 booster doses in co-administration, during the 2021/2022 season. A cross-sectional study analyzing attitudes and factors associated with adherence to influenza and COVID-19 seasonal vaccines co-administration was conducted at the Vaccination Hub of the UH of Palermo, from October to December 2022. Among the 1,263 respondents, 74.7% (n = 944) received the co-administration of seasonal influenza and COVID-19 vaccines. The main reason reported for accepting it was confidence in the recommendations of the Health Ministry (41.3%). At the multivariable analysis, subjects aged ≤ 59 y old (AdjOR: 2.48; CIs95%: 1.89–3.65), male (AdjOR: 1.51; CIs95%: 1.27–1.75), Health-care professionals (HCPs) (AdjOR: 1.66; CIs95%: 1.08–2.57) and those who received co-administration during 2021/2022 (AdjOR: 41.6; CIs95%: 25.5–67.9) were significantly more prone to receive co-administration during 2022/23 season. From data obtained, the role of HCPs in accepting and then promoting co-administration of COVID-19 and influenza vaccines is crucial, as well as receiving co-administration in the previous season that represented the main drive for accepting it in the following seasons, supporting safety and effectiveness of this procedure.

Strong humoral response after Covid-19 vaccination correlates with the common HLA allele A*03:01 and protection from breakthrough infection.

Few data exist on the role of genetic factors involving the HLA system on response to Covid-19 vaccines. Moving from suggestions of a previous study investigating the association of some HLA alleles with humoral response to BNT162b2, we here compared the HLA allele frequencies among weak (n = 111) and strong (n = 123) responders, defined as those healthcare workers with the lowest and the highest anti-Spike antibody levels after vaccination. Individuals with clinical history of Covid-19 or positive anti-nucleocapside antibodies were excluded. We found the common HLA-A*03:01 allele as an independent predictor of strong humoral response (OR = 12.46, 95% CI: 4.41-35.21, p < 0.0001), together with younger age of vaccines (p = 0.004). Correlation between antibody levels and protection from breakthrough infection has been observed, with a 2-year cumulative incidence of 42% and 63% among strong and weak responders, respectively (p = 0.03). Due to the high frequency of HLA-A*03:01 and the need for seasonal vaccinations against SARS-CoV-2 mutants, our findings provide useful information about the inter-individual differences observed in humoral response after Covid-19 vaccine and might support further studies on the next seasonal vaccines.

Inactivated Poliovirus Vaccine Booster Reduces the Likelihood of COVID-19 Outcomes in Individuals Primed with Oral Poliovirus Vaccination.

Introduction: Prior research explores whether seasonal and childhood vaccines mitigate the risk of SARS-CoV-2 infection. Although there are trials investigating COVID-19 infection in response to the effects of the oral poliovirus vaccine (OPV), there has been no prior research assessing COVID-19 outcomes in recently immunized adults with the inactivated poliovirus vaccine (IPV). Methods: SARS-CoV-2 infection and COVID-19 symptoms were analyzed across a cohort of 282 adults who received an IPV booster. Bivariate and multivariate regression models explored associations among variables related to vaccination histories and COVID-19 outcomes. Results: One year post-IPV inoculation, participants who had never received OPV were more likely to test positive for SARS-CoV-2 and experience COVID-19 symptoms, compared to those who had previously received OPV (OR = 3.92, 95%CI 2.22-7.03, p < 0.001; OR = 4.45, 95%CI 2.48-8.17, p < 0.001, respectively). Those who had never received OPV experienced COVID-19 symptoms for 6.17 days longer than participants who had previously received OPV (95%CI 3.68-8.67, p < 0.001). Multivariate regression modeling indicated COVID-19 vaccination did not impact SARS-CoV-2 infection or COVID-19 symptoms in this sample of adults who had recently received IPV. Discussion: Findings suggest IPV may boost mucosal immunity among OPV-primed individuals, and COVID-19 vaccination may not provide additional protection among those who had received IPV. Future, larger-scale studies should measure the extent of protective effects against COVID-19 to inform public health policies in resource-deficient settings.