Motivational interviewing and vaccine acceptance in children: The MOTIVE study

Background and ObjectiveVaccine coverage have been less than desired in young children in part due to parental vaccine hesitancy. Addressing health beliefs through patient-centered communication approaches such as motivational interviewing (MI) may improve vaccine confidence. Thus, the objective of this study was to determine the difference in paediatric vaccination coverage rates based on the Advisory Committee on Immunization Practices (ACIP) and Centers for Disease Control and Prevention (CDC) recommended schedule in children 0–6 years of age after an educational intervention for providers and integration of an MI-based communication tool, MOTIVE (MOtivational Interviewing Tool to Improve Vaccine AcceptancE).MethodsPaediatric and family practice providers in a federally qualified health center in the United States completed an educational intervention regarding vaccine hesitancy and use of the MOTIVE tool. Providers then implemented the MOTIVE tool to address common health beliefs using strong, presumptive vaccine recommendations and an MI framework during encounters with patients 0–6 years of age. Data were collected from 1-year pre-educational intervention (July 2018-June 2019, N = 2504) and post-intervention (July 2019-March 2020, N = 1954) to examine differences in vaccination coverage rates and documented vaccine refusals.ResultsUse of the MOTIVE tool was associated with a statistically significant increase in IIV vaccination coverage rate in children 6 months to 6 years of age (32.4% versus 43.9%, p < 0.01). A significantly increased Hib vaccination coverage rate was observed in children 0–18 months of age. Patients with commercial insurance also had significantly higher vaccination coverage rates for the DTaP, IPV, and VAR vaccines during the intervention period. Use of the MOTIVE tool was associated with a decrease in documented vaccine refusals per 100 patients in children 0–6 years of age (31.5 versus 17.6, p < 0.01).ConclusionUse of an MI-based communication tool may decrease vaccine refusals and improve childhood vaccination coverage rates, particularly for IIV.Clinical Trial Registration: ClinicalTrials.gov, NCT03934008, https://clinicaltrials.gov/ct2/show/NCT03934008, deidentified individual participant data will not be made available.     

Varicella-zoster-virus vaccination of immunosuppressed children with inflammatory bowel disease or autoimmune hepatitis: A prospective observational study

Background and aimsChildren with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS).MethodsThis prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response.ResultsA total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3–16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination.All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn’s disease the day after vaccination.The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078).ConclusionsVZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357).     

Comparison of immunogenicity between candidate influenza A(H3N2) virus vaccine strains in Japan: A randomized controlled trial using a monovalent vaccine of A/Saitama/103/2014 (CEXP-002) and A/Hong Kong/4801/2014 (X-263)

BackgroundFor the 2017–18 influenza season, A/Saitama/103/2014 (CEXP-002) (Saitama strain) was antigenically more similar to prior circulating strains than A/Hong Kong/4801/2014 (X-263) (Hong Kong strain) in a ferret model and was selected as the A(H3N2) vaccine virus strain in Japan. However, the Saitama strain grew poorly, and the Japanese government switched to the Hong Kong strain, raising public concerns of poor effectiveness. To enhance understanding of the correlation between antigenicity in experimental models and immunogenicity, as a surrogate measure of vaccine effectiveness, in the human population, we compared the immunogenicity of specially-prepared single dose monovalent influenza A(H3N2) vaccines containing the Saitama or the Hong Kong strain.MethodsA randomized controlled trial of 100 healthy adults aged 20–64 years (n = 50/group) was conducted. Virus neutralization assay was performed on sera from days 0 (pre-vaccination) and 21 (post-vaccination). Geometric mean titer (GMT), mean fold rise (MFR), seroconversion proportion (SCP), and seroprotection proportion (SPP) were calculated for vaccine strains and a representative circulating A(H3N2) virus strain (A/Osaka/188/2017).ResultsFor the Hong Kong strain, post-vaccination GMT was significantly higher in the Hong Kong vaccine recipients (1:546 vs 1:260, p < 0.01), but MFR, SCP, and SPP were similar for both vaccine groups. For the Saitama strain, post-vaccination GMT (1:116 vs 1:61, p = 0.01) and SPP (86% vs 68%, p = 0.03) were significantly higher in the Hong Kong vaccine recipients, but MFR and SCP were similar for both vaccine groups. Against A/Osaka/188/2017, post-vaccination GMT and MFR were similar in both vaccine groups, but SCP (32% vs 4%, p < 0.01) and SPP (28% vs. 6%, p < 0.01) were significantly higher in the Hong Kong vaccine recipients.ConclusionThe Hong Kong vaccine induced better or equivalent immunogenicity in comparison to the Saitama vaccine. Our trial showed that antigenic similarity in experimental models does not necessarily correlate with immunogenicity in the human population.Clinical trial registration: UMIN000029293.     

Kinetics of pneumococcal antibodies among HIV-exposed,uninfected infants in Botswana

BackgroundStreptococcus pneumoniae is a leading cause of severe infections among children. Despite vaccination, HIV-exposed, uninfected (HEU) children have a higher incidence of invasive pneumococcal disease than HIV-unexposed, uninfected (HUU) children. We sought to compare the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV-13) in HEU and HUU infants.MethodsWe conducted a prospective cohort study of 134 mother-infant dyads in Botswana. Infants received PCV-13 doses at 2, 3, and 4 months through routine clinical care. We measured IgG antibodies specific to vaccine serotypes in sera collected from infants at 0, 5, and 12 months of age. We calculated the proportion of infants with protective IgG levels (≥0.35 µg/mL) to specific pneumococcal serotypes.ResultsAt birth, fewer than half of infants had protective IgG levels to serotypes 1 (38%), 3 (46%), 4 (33%), 5 (23%), 6B (40%), 7F (44%), 9 V (44%), and 23F (46%). Compared to HUU infants (n = 97), HEU infants (n = 37) had lower antibody concentrations at birth to serotypes 5 (p = 0.046) and 19A (p = 0.008) after adjustment for maternal age and infant birth weight. More than 80% of HEU and HUU infants developed protective antibody levels to each of the 13 vaccine serotypes following PCV-13 vaccination. Median concentrations of antibodies to pneumococcal serotypes declined by 55–93% between 5 and 12 months of age, with fewer than half of infants having protective antibody levels to serotypes 1 (47%), 3 (28%), 9 V (44%), 18C (24%), and 23F (49%) at 12 months of age.ConclusionsBoth HEU and HUU infants developed protective antibody responses to PCV-13 administered in a 3 + 0 schedule. However, antibody concentrations to many pneumococcal serotypes waned substantially by 12 months of age, suggesting that a PCV-13 booster dose in the second year of life may be needed to maintain protective pneumococcal antibody levels in older infants and young children.     

A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial

BackgroundAn investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation.MethodsPatients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2–4), 40–80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses.ResultsOf 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6–12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001).ConclusionResults suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial.Trial registrationClinicalTrials.gov, NCT03281876.     

Vaccines do not cause atopic dermatitis: A systematic review and meta-analysis

BackgroundPrevious studies found conflicting results about the association of vaccinations and likelihood of atopic dermatitis (AD).ObjectivesTo determine whether vaccinations increase the likelihood of AD.MethodsA systematic review was performed of all published studies in MEDLINE, EMBASE, LILACS, Scopus, and Web of Science databases. At least 2 reviewers conducted title/abstract, full-text review, and data extraction. Quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS).ResultsForty-four studies met inclusion criteria; 37 had sufficient data for meta-analysis. There were no associations any vaccine regimen (random-effects logistic regression: odds ratio [95% confidence interval]: 0.961 [0.822–1.124]; n = 21 studies) BCG (0.927 [0.701–1.226]; n = 8), pertussis (0.790 [0.416–1.499]; n = 4), single (1.031 [0.920–1.155]; n = 17) or multiple vaccines (0.902 [0.608–1.338]; n = 7) with likelihood of AD. This remained true in studies with high-quality (NOS ≥ 7) (OR [95% CI]: 0.941 [0.793–1.117]; n = 13 studies) or low-quality (NOS < 7) (OR [95% CI]: 1.058 [0.669–1.674]; n = 8 studies).LimitationsNo randomized controlled trials.ConclusionsNo vaccine regimen was consistently associated with developing AD.     

A phase III,observer-blind,randomized, placebo-controlled study of the efficacy,safety, and immunogenicity of SARS-CoV-2 inactivated vaccine in healthy adults aged 18–59 years: An interim analysis in Indonesia

BackgroundThe WHO declared COVID-19 a pandemic on March 11th, 2020. This serious outbreak and the precipitously increasing numbers of deaths worldwide necessitated the urgent need to develop an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The development of COVID-19 vaccines has moved quickly. In this study, we assessed the efficacy, safety, and immunogenicity of an inactivated (SARS-CoV-2) vaccine.MethodsWe conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine and its lot-to-lot consistency. A total of 1620 healthy adults aged 18–59 years were randomly assigned to receive 2 injections of the trial vaccine or placebo on a day 0 and 14 schedule. This article was based on an interim report completed within 3 months following the last dose of study vaccine. The interim analysis includes safety and immunogenicity data for 540 participants in the immunogenicity subset and an efficacy analysis of the 1620 subjects. For the safety evaluation, solicited and unsolicited adverse events were collected after the first and second vaccination within 14 and 28 days, respectively. Blood samples were collected for an antibody assay before and 14 days following the second dose.ResultsMost of the adverse reactions were in the solicited category and were mild in severity. Pain at the injection site was the most frequently reported symptom. Antibody IgG titer determined by enzyme-linked immunosorbent assay was 97.48% for the seroconversion rate. Using a neutralization assay, the seroconversion rate was 87.15%. The efficacy in preventing symptomatic confirmed cases of COVID-19 occurring at least 14 days after the second dose of vaccine using an incidence rate was 65.30%.ConclusionsFrom the 3-month interim analysis, the vaccine exhibited a 65.30% efficacy at preventing COVID-19 illness with favorable safety and immunogenicity profiles.     

Lot-to-lot consistency,safety, tolerability,and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine,in healthy adults aged ≥50 years: A randomized phase 3 trial (PNEU-TRUE)

BackgroundOlder adults are at risk of pneumococcal disease and associated morbidity and mortality. This phase 3 study (V114-020) assessed lot-to-lot consistency across safety and immunogenicity outcomes for V114, a 15-valent pneumococcal conjugate vaccine (PCV), in healthy adults aged ≥ 50 years.MethodsAdults were randomized in a 3:3:3:1 ratio to receive a single dose of one of three lots of V114 or 13-valent PCV (PCV13), stratified by age (50–64 years, 65–74 years, and ≥ 75 years). Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were evaluated at baseline (Day 1) and 30 days post-vaccination. Non-serious and serious adverse events (AEs) were evaluated post-vaccination through 14 days and Month 6, respectively.ResultsOf 2340 participants enrolled, 2282 (97.5%) completed the study. Proportions of participants experiencing ≥ 1 AE were 81.0%, 77.4%, and 78.0% for V114 lots 1, 2, and 3, respectively. Comparison of V114 combined lots with PCV13 showed that proportions of participants experiencing AEs, solicited AEs, and serious AEs were comparable for both vaccines, with the exception of injection-site pain (more frequently reported with V114). OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) at 30 days post-vaccination were comparable across V114 lots, and all lots met predefined equivalence criteria for all 15 vaccine serotypes (lower and upper limits of the 95% confidence intervals of serotype-specific OPA GMT ratios for all possible pairwise comparisons across the three lots were within the equivalence margin of 0.5–2.0). Serotype-specific OPA GMTs and IgG GMCs were comparable in the V114 combined lots and PCV13 groups for the 13 shared serotypes and higher in the V114 group for serotypes unique to V114 (22F and 33F).ConclusionsV114 is well tolerated with a consistent safety profile and immune response across manufacturing lots.Clinical trials registration: NCT03950856 (www.clinicaltrials.gov); 2018-004266-33 (EudraCT).     

Safety and immunogenicity of a pichia pastoris-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine in healthy Chinese women aged 9–45 years: A randomized,double-blind,placebo-controlled phase 1 clinical trial

BackgroundWe evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine.MethodsIn this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9–45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies.ResultsA total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMT_{HPV 16} = 10816 [95 % CI: 7824–14953]), GMT_{HPV 18} = 3966 [95 % CI: 2693–5841]) and high dose group (GMT _{HPV 16} = 14482 [95 % CI: 10848–19333], GMT _{HPV 18} = 3428 [95 % CI: 2533–4639]).ConclusionThe pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9–45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.     

Effects of measles-containing vaccination in children with severe underlying neurologic disease

BackgroundMeasles outbreaks pose significant risk for those unvaccinated.Patients and methodsMeasles-containing vaccine was offered to unvaccinated children with severe neurologic diseases during a measles outbreak. Vaccination adverse events were reported by parents 30 days following vaccination. Long term effects were evaluated 12 months post vaccination.ResultsTwenty-seven children were vaccinated (36 doses given). Half of parents (51.8%) reported no adverse events following immunization. Adverse events included afebrile seizures (6/36), fever alone (5/36) and febrile seizures (5/36). Two children required hospitalization. Quadrivalent measles-containing vaccine combined with varicella was associated with febrile seizures (p = 0.04). No child needed adjustment of the anti-epileptic treatment or exhibited developmental regression.ConclusionIn a series of children with prior severe neurologic disease, the safety-tolerability profile of vaccines containing a measles vaccine component suggests that vaccination is justified. Main side effect was seizure aggravation in children with known epileptic disease.     

A randomized controlled trial of antibody response to 2019–20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults

BackgroundHemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children’s and young adults’ HAI titers against the 2019–2020 LAIV4 and ccIIV4.MethodsParticipants aged 4–21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21–35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers.ResultsGMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4–3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178–237); cell = 136 (95% CI:113–165); LAIV4 day 28: egg = 96 (95% CI: 83–112); cell = 63 (95% CI: 58–74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR.ConclusionThe HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.     

Safety and immunogenicity of a quadrivalent inactivated subunit non-adjuvanted influenza vaccine: A randomized,double-blind,active-controlled phase 1 clinical trial

Quadrivalent influenza inactivated vaccine (IIV4) is more likely to provide wider protection against yearly circulating influenza viruses than trivalent inactivated influenza vaccine (IIV3). In this study, a total of 320 participants were allocated to four age cohorts (6–35 months, 3–8 years, 9–17 years, and ≥ 18 years; 80 participants/cohort) according to their actual date of birth. Participants in each cohort were randomly assigned to two groups to receive intramuscular injection of the trial vaccine or the comparative vaccine in a one-dose (3–8 years, 9–17 years,and ≥ 18 years) schedule on day 0 or two-dose (6–35 months cohort) schedule on day 0 and 28. The first objective is to evaluate the safety and immunogenicity of the full-dose subunit non-adjuvanted IIV4 (FD-subunit NAIIV4) we developed versus an active-control, China-licensed split-virion NAIIV4, in people ≥ 3 years. The second objective is to evaluate the safety and immunogenicity of FD-subunit NAIIV4 versus the half-dose (HD-subunit NAIIV4) in toddlers aged 6–35 months. Results showed that all adverse reactions noted were rare, mild, and self-limited. In ≥ 3 years cohorts, systemic adverse reactions in FD-subunit NAIIV4 groups were less than the active control split-virion NAIIV4 groups ([Systemic adverse reaction rates (95%CI)], 15.0 (8.6–21.4) versus 19.2(12.1–26.2), p = 0.391). The overall seroprotection efficacy after vaccination were comparable between FD-subunit NAIIV4 and the active control split-virion NAIIV4([Seroprotection rates (95%CI)], H1N1, 99.2(81.3–100.0) versus 94.9(90.9–98.9), p = 0.117; H3N2, 81.7(74.7–88.6) versus 82.1(75.1–89.0), p = 0.939; BV, 75.8(68.2–83.5) versus 74.4(66.4–82.3), p = 0.793; BY, 94.2(90.0–98.4) versus 92.3(87.5–97.1), p = 0.568). Additionally, FD-subunit NAIIV4 has comparable safety and better seroprotection versus that of the half-dose in 6–35 months toddlers groups ([Total adverse reaction rates (95%CI)], 37.5(18.5–56.5) versus 47.5(26.1–68.9), p = 0.366) ([Seroprotection rates (95%CI)], H1N1, 85(56.4–100.0) versus 75.7(47.6–100.0), p = 0.117; H3N2, 50(28.1–71.9) versus 29.7(12.2–47.3), p = 0.070; BV, 75(48.2–100.0) versus 29.7(12.2–47.3), p < 0.001; BY, 75(48.2–100.0) versus 56.8(32.5–81.0), p = 0.091). As a result, the FD-subunit NAIIV4 we developed is safe and effective to provide broader and adequate protection against the circulating influenza viruses during 2018–2019, which could be an essential component of the global preventive strategy for influenza pandemic.     

Repeated exposure to an MF-59 adjuvanted quadrivalent subunit influenza vaccine (aQIV) in children: Results of two revaccination studies

BackgroundPediatric adjuvanted seasonal influenza vaccines induce higher immune responses and have the potential to confer better protection against influenza among young vaccine-naïve children. Limited data describe benefits and risks of repeated administration of adjuvanted influenza vaccines in children. Two revaccination studies assess the safety and immunogenicity of repeated exposure to an MF59-adjuvanted quadrivalent influenza vaccine (aQIV; Fluad®) compared to routine non-adjuvanted quadrivalent influenza vaccine (QIV).MethodsChildren previously enrolled in the parent study, who received vaccination with aQIV or nonadjuvanted influenza vaccine (TIV or QIV), were recruited in Season 1 (n = 607) or Season 2 (n = 1601) of the extension trials. Season 1 participants remained in their original randomization groups (aQIV-aQIV or TIV-QIV); Season 2 subjects were re-randomized to either vaccine, resulting in four groups (aQIV-aQIV, aQIV-QIV, QIV-aQIV, or QIV-QIV). All subjects received a single-dose vaccination. Blood samples were taken for immunogenicity assessment prior to vaccination and 21 and 180 days after vaccination. Reactogenicity (Days 1–7) and safety were assessed in all subjects.ResultsHemagglutination inhibition (HI) geometric mean titer (GMT) ratios demonstrated superiority of aQIV revaccination over QIV revaccination for all strains in Season 1 and for A/H1N1, B/Yamagata, and B/Victoria in Season 2. Higher HI titers against heterologous influenza strains were observed after aQIV vaccination during both seasons. Mild to moderate severity and short duration reactogenicity was more common in the aQIV than QIV groups, but the overall safety profiles were similar to the parent study.ConclusionThe safety and immunogenicity results from this study demonstrate benefit of aQIV for both priming and revaccination of children aged 12 months to 7 years.     

COVID-19 vaccine literacy and vaccine hesitancy among pregnant women and mothers of young children in Japan

BackgroundDelays in the spread of vaccination have been recognized as an urgent public health issue in the context of the COVID-19 pandemic. Vaccine literacy (VL) is a critical determinant of vaccine uptake; however, little is known about VL among pregnant women and mothers of young children.MethodsWe analyzed data from a nationwide, cross-sectional internet survey in Japan on VL and vaccine hesitancy, conducted with 1,639 pregnant women and 5,688 mothers of young children who had given birth after July 2019, between July 24 and August 30, 2021.ResultsVaccine hesitancy was observed in 51.1 % of pregnant women and 31.9 % of mothers of young children. The risk of vaccine hesitancy was significantly higher among pregnant women with lower interactive/critical skills (risk ratio [RR] 2.10, 95 % confidence interval [CI] 1.59, 2.78, p < 0.001), although functional skills did not significantly correlate with vaccine hesitancy. For mothers of young children, we found a significantly higher risk of vaccine hesitancy among those with low VL functional skills (RR 1.38, 95 % CI 1.19, 1.61), p < 0.001) and low interactive/critical skills (RR 1.29, 95 % CI 1.10, 1.50, p = 0.001).ConclusionsOur findings suggest that aiding individuals to correctly evaluate vaccine-related information is critical for improving vaccine acceptance rates among both pregnant women and mothers of young children. Meanwhile, improving the comprehensibility of communication toolkits may be important for women with children but have a limited effect among pregnant women.     

Impact of prior vaccination on antibody response and influenza-like illness among Australian healthcare workers after influenza vaccination in 2016

BackgroundEpidemiological studies suggest that influenza vaccine effectiveness decreases with repeated administration. We examined antibody responses to influenza vaccination among healthcare workers (HCWs) by prior vaccination history and determined the incidence of influenza infection.MethodsHCWs were vaccinated with the 2016 Southern Hemisphere quadrivalent influenza vaccine. Serum samples were collected pre-vaccination, 21–28 days and 7 months post-vaccination. Influenza antibody titres were measured at each time-point using the haemagglutination inhibition (HI) assay. Immunogenicity was compared by prior vaccination history.ResultsA total of 157 HCWs completed the study. The majority were frequently vaccinated, with only 5 reporting no prior vaccinations since 2011. Rises in titres for all vaccine strains among vaccine-naïve HCWs were significantly greater than rises observed for HCWs who received between 1 and 5 prior vaccinations (p < 0.001, respectively). Post-vaccination GMTs against influenza A but not B strains decreased as the number of prior vaccinations increased from 1 to 5. There was a significant decline in GMTs post-season for both B lineages. Sixty five (41%) HCWs reported at least one influenza-like illness episode, with 6 (4%) identified as influenza positive.ConclusionsVarying serological responses to influenza vaccination were observed among HCWs by prior vaccination history, with vaccine-naïve HCWs demonstrating greater post-vaccination responses against A(H3N2).     

Immunogenicity and safety of the RTS,S/AS01 malaria vaccine co-administered with measles,rubella and yellow fever vaccines in Ghanaian children: A phase IIIb,multi-center,non-inferiority,randomized, open,controlled trial

BackgroundTo optimize vaccine implementation visits for young children, it could be efficient to administer the first RTS,S/AS01 malaria vaccine dose during the Expanded Programme on Immunization (EPI) visit at 6 months of age together with Vitamin A supplementation and the third RTS,S/AS01 dose on the same day as yellow fever (YF), measles and rubella vaccines at 9 months of age. We evaluated the safety and immunogenicity of RTS,S/AS01 when co-administered with YF and combined measles-rubella (MR) vaccines.MethodsIn this phase 3b, open-label, controlled study (NCT02699099), 709 Ghanaian children were randomized (1:1:1) to receive RTS,S/AS01 at 6, 7.5 and 9 months of age, and YF and MR vaccines at 9 or 10.5 months of age (RTS,S coad and RTS,S alone groups, respectively). The third group received YF and MR vaccines at 9 months of age and will receive RTS,S/AS01 at 10.5, 11.5 and 12.5 months of age (Control group). All children received Vitamin A at 6 months of age. Non-inferiority of immune responses to the vaccine antigens was evaluated 1 month following co-administration versus RTS,S/AS01 or EPI vaccines (YF and MR vaccines) alone using pre-defined non-inferiority criteria. Safety was assessed until Study month 4.5.ResultsNon-inferiority of antibody responses to the anti-circumsporozoite and anti-hepatitis B virus surface antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus RTS,S/AS01 alone was demonstrated. Non-inferiority of antibody responses to the measles, rubella, and YF antigens when RTS,S/AS01 was co-administered with YF and MR vaccines versus YF and MR vaccines alone was demonstrated. The safety profile of all vaccines was clinically acceptable in all groups.ConclusionsRTS,S/AS01 can be co-administered with Vitamin A at 6 months and with YF and MR vaccines at 9 months of age during EPI visits, without immune response impairment to any vaccine antigen or negative safety effect.     

A phase 1 dose-sparing,randomized clinical trial of seasonal trivalent inactivated influenza vaccine combined with MAS-1, a novel water-in-oil adjuvant/delivery system

BackgroundNew influenza vaccines are needed to increase vaccine efficacy. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational low viscosity, free-flowing, water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets.MethodsA phase 1, double-blind, safety and immunogenicity, HA dose escalation, randomized clinical trial was conducted. MAS-1 adjuvant with 1, 3, 5 or 9 µg per HA derived from licensed seasonal trivalent high dose inactivated influenza vaccine (IIV, Fluzone HD 60 µg per HA) in a 0.3 mL dose were compared to standard dose IIV (Fluzone SD, 15 µg per HA). Safety was measured by reactogenicity, adverse events, and clinical laboratory tests. Serum hemagglutination inhibition (HAI) antibody titers were measured for immunogenicity.ResultsSeventy-two subjects, aged 18–47 years, received one dose of either 0.3 mL adjuvanted vaccine or SD IIV intramuscularly. Common injection site and systemic reactions post-vaccination were mild tenderness, induration, pain, headache, myalgia, malaise and fatigue. All reactions resolved within 14 days post-vaccination. Safety laboratory measures were not different between groups. Geometric mean antibody titers, geometric mean fold increases in antibody titer, seroconversion rates and seroprotection rates against vaccine strains were in general higher and of longer duration (day 85 and 169 visits) with MAS-1-adjuvanted IIV at all doses of HA compared with SD IIV. Adjuvanted vaccine induced higher antibody responses against a limited number of non-study vaccine influenza B and A/H3N2 viruses including ones from subsequent years.ConclusionMAS-1 adjuvant in a 0.3 mL dose volume provided HA dose-sparing effects without safety concerns and induced higher HAI antibody and seroconversion responses through at least 6 months, demonstrating potential to provide greater vaccine efficacy throughout an influenza season in younger adults. In summary, MAS-1 may provide enhanced, more durable and broader protective immunity compared with non-adjuvanted SD IIV.Clinical Trial Registry: ClinicalTrials.gov # NCT02500680.     

Impact of rotavirus vaccine on paediatric rotavirus hospitalisation and intussusception in New Zealand: A retrospective cohort study

BackgroundRotavirus results in a significant burden of hospitalisations and deaths globally. Rotavirus vaccine has been used in New Zealand since July 2014. The aim of this study was to assess the safety and effectiveness of RotaTeq® vaccine in New Zealand between 2006 and 2016.MethodsA national cohort study of 723,695 children aged less than 6 years was carried out using linked administrative datasets. Study outcomes were hospitalisation for intussusception, rotavirus, and all-cause gastroenteritis. Intussusception hospitalisation rates were calculated from 2006 to 2016, and rotavirus and all-cause gastroenteritis hospitalisation rates from 2011 to 2016. We examined the effect of RotaTeq® vaccination on rotavirus and all-cause gastroenteritis hospitalisation rates using Poisson regression. Adjusted incidence rate ratios controlled for sex, year of birth, ethnicity, socioeconomic deprivation, and district health board area.ResultsSignificant reductions in the incidence of rotavirus hospitalisation were seen in all age groups, ethnicities, and deprivation following the introduction of RotaTeq®. There was a 92.6% reduction in hospitalisation incidence in the vaccinated cohort (p < 0.0001). There was also a 48% reduction in all-cause gastroenteritis hospitalisation incidence in the vaccinated cohort (p < 0.0001). The average annual intussusception rate in children aged less than 3 years was 26.2 per 100,000, with no significant change over time (p = 0.847).ConclusionsIn New Zealand the introduction of RotaTeq® resulted in a significant reduction in rotavirus hospitalisation, and a halving in all-cause gastroenteritis hospitalisation. There has been no change in the overall incidence of intussusception or clear change in patterns of cases, although intussusception cases did occur within risk period immediately post vaccine.     

COVID-19 vaccination hesitancy in people affected by diabetes and strategies to increase vaccine compliance: A systematic narrative review and meta-analysis

IntroductionPeople affected by diabetes are at higher risk for complications from certain vaccine-preventable diseases. Suboptimal vaccination coverages are reported in this population sub-group. The purpose of this study is to estimate the proportion of diabetic patients who express hesitation to the COVID-19 vaccine worldwide.MethodsSeven studies were included in the meta-analysis and systematic review, selected from scientific articles available in the MEDLINE/PubMed, Google Scholar and Scopus databases from 2020 to 2022. The following terms were used for the search strategy: (adherence OR hesitancy OR compliance OR attitude) AND (covid* OR SARS*) AND (vaccin* OR immun*) AND (diabet*).ResultsThe vaccine hesitation rate among persons with diabetes was 27.8 % (95 %CI = 15.6–41.9 %). In the comparison of vaccine hesitancy between sexes and educational status, the RRs were 0.90 (95 %CI = 0.71–1.15) and 0.88 (95 %CI = 0.76–1.02), respectively. The main reasons of unwillingness were lack of information, opinion that the vaccine was unsafe or not efficient, and fear of adverse events.ConclusionsIn order to achieve a high vaccination coverage, multifactorial approach is needed, which requires major social, scientific and health efforts. The success of the vaccination campaign in this population depends on the capillarity and consistency of the interventions implemented.     

Association between vaccination status,symptom identification and healthcare use: Implications for test negative design observational studies

AimTo test the internal validity of the test-negative design (TND) by investigating associations between maternal influenza vaccination, and new virus detection episodes (VDEs), acute respiratory illness, and healthcare visits in their children.MethodsEighty-five children from a birth cohort provided daily symptoms, weekly nasal swabs, and healthcare use data until age 2-years. Effect estimates are summarised as incidence rate ratios (IRR).ResultsThere was no association between maternal vaccination and VDEs in children (IRR = 1.1; 95 %CI = 0.9–1.2). Influenza-vaccinated mothers were more likely than unvaccinated mothers to both report, and seek healthcare for, acute lower respiratory illness in their children, IRR = 2.4; 95 %CI = 1.2–4.8 and IRR = 2.2; 95 %CI = 1.1–4.3, respectively.ConclusionA key assumption of the TND, that healthcare seeking behaviour for conditions of the same severity is not associated with vaccine receipt, did not hold. Further studies of the performance of the TND in different populations are required to confirm its validity.