Vaccine

BackgroundRoutine childhood vaccination improves health and prevents morbidity and mortality from vaccination preventable diseases. There are indications that the COVID-19 pandemic has negatively impacted vaccination rates globally, but systematic studies on this are still lacking in Canada. This study aims to add knowledge on the effect of the pandemic on pneumococcal vaccination rates of children using self-reported immunization data entered into the CANImmunize digital vaccination tool. MethodologyAn interrupted time series analysis was conducted on aggregated monthly enrollment of children on the platform (2016-2021) and their pneumococcal immunization series completion rates (2016-2020). Predicted trends before and after the onset of the COVID-19 related restriction (March 1, 2020) were compared by means of an Autoregressive Integrated Moving Average (ARIMA). ResultsPandemic restrictions were associated with changes in self-reported pneumococcal immunization rates amongst the users of the CANImmunize platform. The monthly enrollment of children on the platform decreased by - 1177.52 records (95% CI: -1865.47, - 489.57), with a continued decrease of 80.84 records each month. Self-reported pneumococcal immunization series completion rates had an immediate increase of 14.57% (95% CI 4.64, 24.51) followed by a decrease of -3.54% each month. ConclusionThe onset of the COVID-19 related restrictions impacted enrollment of children in the CANImmunize digital immunization platform, and an overall decrease in self-reported pneumococcal immunization series completion rates. Our findings support that efforts to increase catch-up immunization campaigns so that children who could not get scheduled immunization during the pandemic are not missed.

BackgroundThe COVID-19 pandemic has greatly affected nursing home residents (NHRs), a vulnerable group with high rates of illness and death. While vaccination is essential for reducing infections and severe outcomes in the short term, it is important to understand how long antibody levels and neutralizing activity last. This understanding will help us create effective public health strategies for the long term. According to current CDC guidelines, individuals over the age of 65 should receive a booster dose six months after their previous vaccination. MethodsThis observational retrospective cohort study analyzed post-vaccination serum from samples with up to 400 days of follow-up from 697 NHRs and 127 healthcare workers (HCWs) across Northeast Ohio and Rhode Island. Analyses were conducted to model decay rates of both neutralizing and binding antibody titers and the impact of previous exposures to SARS-CoV-2 on these decay rates. ResultsResults indicate that NHRs show Wuhan and Omicron BA.4/5 neutralizing and binding antibody titers diminish significantly from 2 weeks to 12 months post-vaccination. NHRs with prior infection show higher peak antibody titers and slower decay than those naive to infection. Antibody levels after vaccination for infection-naive NHR residents lagged HCW and NHR with prior infection, but then decayed at a similar rate. ConclusionThe immunologic findings in this cohort of NHR are in line with the existing real-world clinical effectiveness data in older individuals and support the CDC recommendation of a bi-annual vaccination to reduce severe COVID-19 outcomes in persons age 65 and older.

BackgroundEstimating attributable risk (AR) through self-controlled case series (SCCS) analyses alone may limit generalizability because SCCS only incorporate vaccinated patients with the outcome (e.g., Guillain-Barre syndrome [GBS]) who may differ from the overall population recommended for vaccination. ObjectiveWe aimed to demonstrate background event incidence rates impact on vaccine-specific GBS ARs and to standardize ARs across different vaccine studies by applying a generalizable, population-based GBS background rate for improved comparability and to better estimate the expected population-level ARs. MethodsWe identified post-licensure SCCS vaccine studies and GBS background rates using US Medicare data via targeted literature review. GBS control period rates from SCCS vaccine studies were extracted or calculated. Population-level ARs were calculated for each vaccine using published background GBS rates and the original SCCS-generated incidence rate ratios (IRRs). ResultsPublished vaccine-specific GBS IRRs ranged from 2.02 (95%CI: 0.93-4.40) for RSVPreF to 4.96 (95%CI: 1.43-17.27) for recombinant zoster vaccine (RZV). Study-specific ARs per 100,000 doses ranged from 0.28 (H1N1) to 0.90 (RSVPreF). Vaccines with lower control period GBS rates had a lower attributable risk for a given IRR. After standardization using published background GBS rates, population-level ARs were higher for vaccines with higher IRRs. For example, when using the H1N1 vaccine control period rate as the GBS background rate for AR calculation, RSVPreF had the lowest AR per 100,000 doses (0.21) and RZV the highest (2.37). ConclusionAR calculation is dependent on the control period rate within a given SCCS analysis. ARs derived exclusively from SCCS analyses may lead to incorrect conclusions regarding an adverse events absolute risk if included in product labels due to a lack of external validity. Using a representative background rate from the recommended vaccinee population, along with SCCS-derived IRR, to calculate the expected population-level AR may offer more accurate vaccine risk-benefit assessments.

The 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) were previously recommended for adults in the United States. To help inform discussions on recently licensed 15- and 20-valent pneumococcal vaccine use among adults, we conducted a systematic review of PCV13 and PPSV23 efficacy or effectiveness. We conducted a search on PCV13 and PPSV23 efficacy or effectiveness (VE) studies against vaccine type (VT) invasive pneumococcal disease (IPD) and VT-pneumococcal pneumonia in adults. Nineteen studies were included: 13 on VT-IPD (four on PCV13, nine on PPSV23) and eight on VT-pneumococcal pneumonia (three on PCV13, four on PPSV23, one on PCV13 and PPSV23). One randomized-controlled trial (RCT) evaluated PCV13 and observed an efficacy of 75% and 45% against VT-IPD and VT-pneumococcal pneumonia, respectively. No RCTs reported PPSV23 efficacy. PCV13 effectiveness estimates against VT-IPD ranged from 47% to 68%. Pooled PPSV23 effectiveness against VT-IPD was 45% (95% CI: 37%, 51%; I2=0%). PCV13 VE estimates against VT-pneumonia ranged from -2 to 46%. Pooled PPSV23 VE against VT-pneumococcal pneumonia was 18% (95% CI: -4%, 35%; I2=0%). Evidence suggests PCV13 and PPSV23 are effective against VT-IPD and VT-pneumococcal pneumonia in adults; this was used to inform PCV15 and PCV20 policy decisions.

The emergence of SARS-CoV-2 variants continues to be a major obstacle for controlling the global pandemic. Despite the currently authorized SARS-CoV-2 vaccines ability to reduce severe disease and hospitalization, new immunization strategies are needed that enhance mucosal immune responses, inhibit community transmission, and provide protection against emerging variants. We have developed a mucosally delivered, non-replicating recombinant adenovirus vector (rAd5) vaccine, that has proven efficacy in the clinic against other respiratory viruses [1]. Here we evaluated the immunogenicity of three candidate SARS-CoV-2 vaccines in cynomolgus macaques that contained spike (S) and/or nucleocapsid (N) from either the Wuhan or the beta variant to select a candidate for future clinical development. Mucosal immunization with the Wuhan specific S vaccine (ED90) induced significant cross-reactive serum IgG responses against to Wuhan, beta, gamma and delta lineages, and generated substantial serum neutralizing activity. In nasal samples, ED90 immunization induced 1000-fold increases in IgA to all variants of concern tested and had neutralizing activity against Wuhan and delta. While immunization with the beta specific vaccine (ED94) enhanced IgG and IgA responses to homologous beta variant S and RBD, this approach resulted in less cross-reactive responses to other variants in the serum and nasal passages compared to ED90. As ED90 immunization induced the most robust cross-reactive systemic and mucosal antibody responses, this candidate was chosen for future clinical development.

BackgroundWhole-cell pertussis (wP) and acellular pertussis (aP) vaccines evoke different immune responses to pertussis vaccine antigens. We compared the effect of a heterologous wP/aP/aP primary series (hereafter mixed wP/aP) versus a homologous aP/aP/aP primary schedule (hereafter aP-only) on antibody responses to co-administered vaccine antigens in infants and toddlers. MethodsWe randomised Australian infants in a 1:1 ratio to receive either a mixed wP/aP schedule (pentavalent diphtheria-tetanus-wP-hepatitis B-Haemophilus influenzae type b; DTwP-HepB-Hib vaccine at 6 weeks old followed by hexavalent DTaP-inactivated poliovirus vaccine (IPV)-HepB-Hib vaccine at 4 and 6 months old) or to aP-only priming doses of hexavalent DTaP-IPV-HepB-Hib vaccine at the same ages. All infants received 13-valent pneumococcal conjugate vaccine (13vPCV) at 6 weeks, 4 and 12 months of age and DTaP-IPV and Hib vaccine boosters at 18 months. We estimated the ratio (GMR) of IgG geometric mean concentrations (GMCs) in the wP/aP and aP-only groups for the serotypes included in the 13vPCV, for Hib capsular polysaccharide polyribosylribitol phosphate (PRP), and for hepatitis B surface antigen (HBsAg) at 6, 7, 18, and 19 months. We assessed whether the wP/aP schedule is non-inferior to the aP-only schedule for co-administered vaccine antigens (GMR>2/3). Trial registration: ACTRN12617000065392p. ResultsBetween March 2018 and January 2020, 150 infants were randomised (75 per study arm). Responses to all 13vPCV serotypes and Hib-PRP at 6, 7, 18, and 19 months old, as well as HBsAg at 6 and 7 months old were non-inferior (>90% probability). Sera GMCs were higher for each 13vPCV serotype, Hib-PRP, and HBsAg at each timepoint in the wP/aP group than in the aP-only group. InterpretationA mixed wP/aP schedule resulted in non-inferior IgG responses to co-administered vaccine antigens compared to the standard aP-only schedule for pertussis primary immunisation. FundingTelethon New Childrens Hospital Research Fund and National Health and Medical Research Council. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSCombination vaccines incorporate antigens that protect against multiple diseases into a single injection. Most low- and middle-income countries (LMICs) currently use wP combination vaccines. Due to the need for periodic boosters to protect older children, adolescents, and adults, these countries may consider moving to the less reactogenic aP combination vaccines that are routinely used in most high-income countries. We searched for evidence about whether a mixed wP/aP primary schedule impacts the immunogenicity of co-administered vaccines. We were particularly interested in evidence for impacts on 13vPCV 2 + 1 schedule and other pneumococcal dose-sparing schedules. We searched PubMed on May 23, 2024, for randomised controlled trials using the following search terms "pneumococcal", "routine vaccin*", and "pertussis" combined with Boolean operators, without date or language restrictions. We failed to identify any head-to-head randomised comparisons of the effect of heterologous (mixed) versus homologous pertussis vaccine primary series on co-administered vaccine antigens. Our previous meta-analysis reviewed 15 randomised controlled studies that compared serious adverse events among infants receiving wP versus aP as a first dose before 6 months of age. Few studies reported immune responses to non-DTP co-administered antigens. These findings suggest enhanced Hib responses among recipients of a three-dose primary series of wP compared to those who received three primary aP doses, non-inferior Hib-PRP seroprotection among aP compared to wP vaccinees, and mixed results regarding HBsAg-IgG levels post-wP priming. Both wP and aP groups exhibited weaker Hib-PRP IgG responses when DTP-Hib vaccines were co-administered with meningococcal serogroup C vaccine conjugated to cross-reactive material 197 (CRM197) compared to the meningococcal serogroup C vaccine conjugated to tetanus toxoid (TT). Added value of this studyThis paper is the first reported evidence of a mixed wP/aP schedule resulting in non-inferior IgG responses to co-administered vaccine antigens compared to the standard homologous aP-only schedule for pertussis primary immunisation. In addition, enhanced immune responses were observed to all serotypes included in the 13vPCV and Hib-PRP vaccines in children receiving the mixed wP/aP vaccination strategy versus those vaccinated with a standard aP-only schedule. Implications of all the available evidenceIn settings transitioning from using wP to aP multi-component vaccines, infants receiving a mixed schedule (with wP as the first dose) can be expected have non-inferior, and possibly superior, antibody responses to concomitant vaccine antigens. To better understand the underlying mechanisms of our findings, the assessment of opsonophagocytic activity response rates and serotype-specific memory B cell immune responses to PCV antigens is required. Large population-based studies, particularly in countries where pneumococcal and Hib disease burdens remain high, should be conducted to determine if the observed effects on immune responses translate into differences in protection against disease.

IntroductionIn August 2021, Thailand imported the BNT162b2 mRNA COVID-19 vaccine. The prioritised group to receive the BNT162b2 vaccine were health professionals. The BNT162b2 vaccine scheduled for healthcare workers were two-dose regimen administered three weeks apart, the third dose booster in two-dose inactivated CoronaVac vaccine recipients or as a second dose in health professionals who had received the CoronaVac or adenoviral-vectored (ChAdOx1-S) vaccine as the first dose regardless of the interval between the first and second dose. MethodsThis study aims to evaluate the immunogenicity of the heterologous prime boost CoronaVac followed by BNT162b2 in health professionals. ResultsThe CoronaVac/BNT162b2 vaccine recipients elicited higher neutralizing activity against the original Wuhan and all variants of concern than in the recipients of the two-dose CoronaVac. ConclusionsThe heterologous CoronaVac/BNT162b2 could be used as an alternative regimen in countries experiencing the vaccine shortages and in individuals experiencing the adverse events following CoronaVac.

It is recognised that many observational studies and randomised control trials reporting high efficacy for Covid-19 vaccines suffer from various biases. Systematic review identified thirty-seven studies that suffered from one particular and serious form of bias called miscategorisation bias, whereby study participants who have been vaccinated are categorised as unvaccinated up to and until some arbitrarily defined time after vaccination occurred. Simulation demonstrates that this miscategorisation bias artificially boosts vaccine efficacy and infection rates even when a vaccine has zero or negative efficacy. Furthermore, simulation demonstrates that repeated boosters, given every few months, are needed to maintain this misleading impression of efficacy. Given this, any claims of Covid-19 vaccine efficacy based on these studies are likely to be a statistical illusion or are exaggerated.

IntroductionThe Immunization Agenda 2030 calls for reaching all people with immunization services, including zero-dose children--children who have not received any routine vaccines. To plan and finance efforts to fully vaccinate these children and improve coverage and equity, decision-makers need reliable cost estimates. However, primary data on the costs of reaching zero-dose children, typically part of disadvantaged and hard-to-reach populations, are scarce. This study approximates these costs using standardized, country-level estimates of vaccine delivery unit costs for outreach delivery in low- and middle-income countries (LMICs). MethodsWe extracted outreach delivery cost-per-dose estimates for childhood immunization services from the 2024 update of the Immunization Delivery Cost Catalogue. Using these data, we developed a meta-regression model to estimate standardized outreach vaccine delivery unit costs. The generalized linear model assumed a Gamma-distributed outcome with a log link and included both country-level and study-level predictors: study year, economic or financial cost basis, routine or campaign delivery, and full or incremental costing approach. The fitted model was used to estimate 2024 outreach delivery costs per dose for 129 LMICs. ResultsThe model was estimated using 48 observations from 19 countries focused on outreach or mobile vaccine delivery. The best-fitting specification included diphtheria-tetanus-pertussis (DTP1) coverage, per-capita gross domestic product, and under-five population size as predictors. For 2024, the predicted mean economic cost per dose was $8.65 (95% uncertainty interval $2.33-23.71), averaged across all 129 LMICs. To fully immunize a zero-dose child with 13 recommended vaccinations, the equivalent cost estimate was $112.45 ($30.29-308.23). ConclusionReaching zero-dose children is crucial for improving equity in global health, and estimates of the costs of doing so are needed to inform budgeting for immunization programs. These meta-regression-based cost estimates can help countries to improve budgeting, planning, and resource allocation for efforts to reach zero-dose children. O_LIWhat is already known on this topic C_LI {circ}Despite global commitments under the Immunization Agenda 2030, millions of "zero-dose" children in low- and middle-income countries (LMICs) remain unvaccinated, often due to poverty, geographic inaccessibility, or conflict. {circ}Few studies have directly quantified the costs of reaching zero-dose children; existing evidence is fragmented and limited to small-scale or country-specific interventions. O_LIWhat this study adds C_LI {circ}Using a Bayesian meta-regression framework, this study estimates standardized, country-level estimates of vaccine delivery costs based on data for outreach delivery--a proxy for the costs of reaching zero-dose children. {circ}The analysis estimates an average 2024 economic cost of $8.65 per dose and $112.45 per fully vaccinated zero-dose child across 129 LMICs. O_LIHow this study might affect research, practice or policy C_LI {circ}This study provides an evidence base to estimate the investments needed to close immunization coverage gaps under the Immunization Agenda 2030.

BackgroundReliable estimates of immunization delivery costs are essential for planning, budgeting, and economic evaluation of vaccination programs. Although a number of empirical costing studies have been conducted in recent years, many low- and middle-income countries (LMICs) continue to lack up-to-date, accurate delivery unit cost estimates--particularly for adolescent and campaign vaccination strategies. Building on prior work, this study aimed to produce updated, standardized country-level estimates of immunization delivery unit costs for different vaccination modalities across all LMICs. MethodsUsing data on study-level unit cost estimates reported by empirical costing studies in the 2024 update of the Immunization Delivery Cost Catalogue, we fitted Bayesian meta-regression models predicting per-dose delivery costs for routine childhood vaccination, routine adolescent vaccination (using human papillomavirus vaccination as a proxy), and vaccination delivered via mass campaigns. Regression models incorporated country-level covariates (per-capita gross domestic product, population size, third-dose diphtheria-tetanus-pertussis vaccination coverage, urbanization, population density, and under-five mortality) and study-level characteristics (cost category, financial versus economic costing perspective, and full versus incremental costing methodology). Fitted models were used to generate country-specific and population-weighted average economic and financial cost per dose estimates for 2024, in 2024 US dollars. ResultsThe analysis included 142 observations for routine childhood vaccination, 63 observations for routine adolescent vaccination, and 113 observations for campaign vaccination. For 2024, the population-weighted mean economic cost per dose across all LMICs was estimated at $5.86 (95% uncertainty interval: $2.74-13.43) for routine childhood vaccination, $17.65 ($7.76-44.30) for routine adolescent vaccination, and $3.13 ($2.03-4.78) for campaign vaccination. Corresponding financial costs per dose were $3.02 ($1.52-6.29), $10.08 ($4.15-25.01), and $1.79 ($1.11-2.91), respectively. Substantial heterogeneity in delivery costs was observed across countries, delivery modalities, and cost perspectives. The estimated associations between predictors and unit costs may be influenced by unobserved study characteristics, and therefore should be interpreted as correlational rather than causal. ConclusionsBy leveraging an expanded empirical evidence base and a Bayesian meta-regression framework, this study provides updated per-dose delivery costs for routine childhood vaccination and estimates new per-dose delivery costs for routine adolescent vaccination and campaign vaccination. As policy decisions often must be made despite incomplete information, these estimates provide a practical source of evidence to support analyses when direct cost data are unavailable.

Participants in studies investigating COVID-19 vaccines commonly report reactogenicity events, and concerns about side effects may lead to reluctance to receive updated COVID-19 vaccinations. A real-world, post hoc analysis, observational 2019nCoV-406 study, was conducted to examine reactogenicity within the first 2 days after vaccination with either a protein-based vaccine (NVX-CoV2373) or an mRNA vaccine (BNT162b2 or mRNA-1273) in individuals who previously completed a primary series. Propensity score adjustments were conducted to address potential confounding. The analysis included 1130 participants who received a post-primary series dose of NVX-CoV2373 (n = 303) or an mRNA vaccine (n = 827) during the study period. Within the first 2 days after vaccination, solicited systemic reactogenicity events (adjusted) were reported in 60.5% of participants who received NVX-CoV2373 compared with 84.3% of participants who received an mRNA vaccine; moreover, 33.9% and 61.4%, respectively, reported [≥]3 systemic reactogenicity symptoms. The adjusted mean (95% CI) number of systemic symptoms was 1.8 (1.6-2.0) and 3.2 (3.0-3.4), respectively. Local reactogenicity events (adjusted) were reported in 73.4% and 91.7% of participants who received NVX-CoV2373 and mRNA vaccines, respectively; the adjusted mean (95% CI) number of local symptoms was 1.5 (1.33-1.61) and 2.4 (2.31-2.52), respectively. These results support the use of adjuvanted, protein-based NVX-CoV2373 as an immunization option with low reactogenicity.

People with weak immune systems are more likely to develop severe COVID-19, less likely to be included in vaccine controlled studies but more likely to be under-vaccinated. We review post-marketing studies to examine the immunogenicity, safety and effectiveness of BNT162b2 vaccine in immunocompromised adolescents and young adults (AYA). We searched more than three international databases from 2020 to 30 May 2022 and used the ROBINS-I for bias assessment. Random effect model was used to estimate pooled proportion, log RR, and mean difference. Eggers regression and Beggs rank correlation were used to examine publication bias. 47 full texts were reviewed, and nine were included. Conditions studied were rheumatic diseases, diabetes mellitus, Down syndrome, solid tumours, neurodisability, and cystic fibrosis. Eight studies used cohort designs and one used cross-sectional designs. Europe led most of the investigations. Most studies had unclear risk of bias and none could rule out selection bias, ascertainment bias, or selective outcome reporting. The overall estimated proportion of combined local and systemic reactions after the first BNT162b2 vaccination was 30%[95% CI: 17-42%] and slightly rose to 32% [95% CI: 19-44%] after the second dose. Rheumatic illnesses had the highest rate of AEFI (40%[95% CI: 16-65%]), while cystic fibrosis had the lowest (27%[95% CI: 17%-38%]). Hospitalizations for AEFIs were rare. Healthy controls exhibited higher levels of neutralizing antibodies and measured IgG than immunocompromised AYA, although pooled estimations did not demonstrate a statistically significant difference after primary dose. BNT162b2 is safe and effective in immunocompromised AYA, with no significant difference to healthy controls. However, current evidence is low to moderate due to high RoB. Our research advocates for improving methodology in studies including specific AYA population.

Recently SARS-CoV-2 Omicron (B.1.1.529) variant was identified in South Africa with numerous mutations in spike protein, and numerous community infections have been reported and raised grave concern around the world. Some studies found that the neutralization effects of several licensed vaccines against Omicron were dramatically reduced, which significantly affected antibody mediated protection, especially for individuals whose immunization were completed after extended period. In this regard, we studied the persistence and neutralization activity toward mutant strains in animal serum immunized with PIKA-adjuvanted recombinant SARS-CoV-2 spike protein subunit vaccine (YS-SC2-010). Here we are reporting that animal serum collected at 596 days after immunization with YS-SC2-010 still retains high and persistent neutralizing activity against all the Variant of Concern (VOC) variants, including Omicron variant. Although it is a blessed event to achieve 20 months long neutralization against Omicron variant after immunization with YS-SC2-010, it was also founded that the neutralization effect of immune serum on Omicron decreased by 6.29 folds as compared to D614G, more significantly when compared with other mutant strains.

BACKGROUNDCOVID-19 vaccines exhibit real-world waning effectiveness against SARS-CoV-2 infection within the first 3-6 months after a completed series. Consequently, the main metric tracked by the CDC (percent "fully vaccinated," with no adjustment for booster status) has become insufficiently informative. METHODSWe analyzed CDC daily vaccination data to quantify COVID-19 immunization status for 4 mutually-exclusive groups: (1) not immunized; (2) partially immunized (people who received the 1st dose of a 2-dose series); (3) immunized with waning immunity (previously immunized people whose booster dose is overdue); and (4) optimally immunized (people who: (a) received the Janssen vaccine <2 months ago or completed an mRNA vaccine series <6 months ago, or (b) received the Janssen vaccine >2 months ago or completed an mRNA vaccine series >6 months ago and received a booster dose.) RESULTSThe proportion of the total US population who were optimally immunized against COVID-19 fell from a high of 45.3% on July 17 to 29.4% on November 30. During November, the majority of states experienced a worsening trend in the percent of the total population who were overdue for a booster dose, including the 4 largest states, with percentage point increases of 3.5 in New York, 3.4 in California, 2.3 in Texas and 1.7 in Florida. CONCLUSIONSOur proposed classification scheme accounts for type-specific vaccine waning intervals, provides an accurate assessment of progress toward national immunization goals, and reveals the urgent need for additional public health mitigation strategies to successfully combat the COVID-19 pandemic in the United States.

BackgroundCOVID-19 vaccination rates among children have stalled, while new coronavirus strains continue to emerge. To improve child vaccination rates, policymakers must better understand parental preferences and reasons for COVID-19 vaccination among their children. Methods and FindingsCross-sectional surveys were administered online to 30,174 US parents with at least one child of COVID-19 vaccine eligible age (5-17 years) between January 1 and May 9, 2022. Participants self-reported willingness to vaccinate their child and reasons for hesitancy, and answered additional questions about demographics, pandemic related behavior, and vaccination status. Willingness to vaccinate a child for COVID-19 was strongly associated with parental vaccination status (multivariate odds ratio 97.9, 95% confidence interval 86.9-111.0). The majority of fully vaccinated (86%) and unvaccinated (84%) parents reported concordant vaccination preferences for their eligible child. Age and education had differing relationships by vaccination status, with higher age and education positively associated with willingness among vaccinated parents. Among all parents hesitant to vaccinate their children, the two most frequently reported reasons were possible side effects (47%) and that vaccines are too new (44%). Among hesitant parents, parental vaccination status was inversely associated with reported lack of trust in government (p<.001) and scientists (p<.001). Cluster analysis identified three groups of hesitant parents based on their reasons for hesitance to vaccinate, with distinct concerns that may be obscured when analyzed in aggregate. ConclusionFactors associated with willingness to vaccinate children and reasons for hesitancy may inform targeted approaches to increase vaccination.

Few studies have assessed the impact of the COVID-19 pandemic on immunization coverage for adolescents, and little is known about how coverage has changed throughout the pandemic. We aimed to: (1) assess the change in coverage for school-based vaccines in Alberta, Canada resulting from the pandemic; (2) determine whether coverage differed by geographic health zone and school type; and (3) ascertain whether coverage has returned to pre-pandemic levels. Using a retrospective cohort design, we used administrative health data to compare coverage for human papillomavirus (HPV) and meningococcal conjugate A, C, Y, W-135 (MenC-ACYW) vaccines in Alberta, Canada between pre-pandemic (2017-2018 school year) and pandemic (2019-2020 and 2020-2021 school years) cohorts (N=289,420). Coverage was also compared by health zone and authority type. The 2019-2020 cohort was followed over one year to assess catch-up. Compared to 2017-2018, immunization coverage for HPV was significantly lower in the 2019-2020 (absolute difference: 60.8%; 95% CI: 60.4-61.3%) and 2020-2021 cohorts (absolute difference: 59.9%; 95% CI: 59.4-60.3%). There was a smaller, significant decline in MenC-ACYW coverage comparing 2017-2018 to 2019-2020 (absolute difference: 6.1%; 95% CI: 5.6-6.5%) and 2020-2021 (absolute difference: 32.2%; 95% CI: 31.6-32.7%). Private schools had low coverage overall, while coverage fluctuated by zone. During follow-up of the 2019-2020 cohort, coverage for HPV and MenC-ACYW increased from 5.6% to 50.2%, and 80.7% to 83.0%, respectively. There was a substantial decrease in school-based immunization coverage during the COVID-19 pandemic, and coverage has not returned to pre-pandemic levels, suggesting further catch-up is needed.

ObjectiveTo compare the reactogenicity and immunogenicity between the two-dose mRNA COVID-19 vaccine regimen and one or two doses of inactivated vaccine followed by an mRNA vaccine regimen in healthy children between 5-11 years of age. MethodsA prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5-11 years of age were enrolled and received the two-dose mRNA COVID-19 vaccine (BNT162b2) regimen or the inactivated (CoronaVac) vaccine followed by the BNT162b2 vaccine regimen. In addition, healthy children who received two doses of BBIBP-CorV between 1-3 months prior were enrolled to receive a heterologous BNT162b2 as a third dose (booster). Reactogenicity was assessed by a self-reported online questionnaire. Immunogenicity analysis was performed to determine binding and surrogate neutralizing antibodies to SARS-CoV-2 wild-type and Omicron variants. ResultsOverall, 166 eligible children were enrolled. Local and systemic AE which occurred within 7 days after vaccination were mild to moderate and well-tolerated. At one-month, post-two or post-three doses, children vaccinated with two-dose BNT162b2, CoronaVac/BNT162b2, and two-dose BBIBP-CorV followed by BNT162b2 elicited similar levels of anti-receptor-binding domain (RBD) IgG. However, the two-dose BNT162b2 and two-dose BBIBP-CorV followed by BNT162b2 groups elicited higher neutralizing activities against Omicron BA.2 variant than the CoronaVac/BNT162b2 group. ConclusionThe heterologous, CoronaVac vaccine followed by the BNT162b2 vaccine, regimen elicited lower neutralizing activities against the emerging Omicron BA.2 variant than the two-dose mRNA regimen. A third dose (booster) mRNA vaccine should be prioritized for this group.

The dominance of SARS-CoV-2 variants of concern (VoC), such as the Omicron subvariants, is a threat to the current vaccination scheme due to increased resistance to immune neutralization and greater transmissibility. To develop the next generation of prefusion SARS-CoV-2 spike protein (S-2P) subunit vaccine adjuvanted with CpG1018 and aluminum hydroxide, mice immunized with two doses of the adjuvanted ancestral Wuhan strain (W) followed by the third dose of the W or Omicron variants (BA.1 or BA.4/BA.5) S-2P, or a combination of the above bivalent S-2Ps. Antisera from mice were tested against pseudovirus neutralization assay of ancestral SARS-CoV-2 (WT) and Omicron BA.4/BA.5 subvariant. Boosting with bivalent mixture of Omicron BA.4/BA.5 and W S-2P achieved the highest neutralizing antibody titers against BA.4/BA.5 subvariant pseudovirus compared to other types of S-2P as boosters.

BackgroundEnterotoxigenic Escherichia coli (ETEC) remains a major cause of diarrheal disease in low- and middle-income countries (LMICs). To curb ETEC related diarrhoea, several candidate vaccines are in development, with ETVAX(R) being the most advanced. Although immunogenicity studies have primarily focused on measuring antibody titres, assessing antibody avidity offers additional valuable insight into antibody quality and immune maturity. This study assessed anti-CS3 and anti-LTB IgG avidity in Zambian children to better understand vaccine-induced antibody responses in an endemic setting. MethodsChildren aged 6-23 months (n=60) received three quarter-doses of ETVAX(R) with dmLT adjuvant on days 0, 14, and 90. Plasma samples collected at baseline (V1), seven days after the second dose (V5), and seven days after the third dose (V7) were analysed by limiting antigen dilution ELISA to calculate avidity indices (AI). Naive classification was performed using titre-based thresholds (20th percentile of baseline titres) and avidity-defined naivety (AI < 0.5). Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory performance of avidity indices against titre-defined naive status. ResultsBaseline avidity was detectable for both CS3 and LTB, consistent with prior natural exposure. Mean CS3 IgG avidity decreased from 0.7 at baseline to 0.6 after the third dose (p<0.001), while LTB IgG avidity showed transient decreases but no net gain. Naive classification at baseline revealed that 9/60 children had titres but low avidity (functional naivety), and 6/60 had waned titres but high avidity. Only one child was naive by both criteria for CS3, and none for LTB. ROC analysis demonstrated moderate discrimination for CS3 (AUC=0.65; optimal cut-off AI=0.36) but poor discrimination for LTB (AUC=0.30). ConclusionIn this endemic population, ETVAX(R) induced strong antibody titres but minimal changes in avidity over time with inter-individual differences, while ROC analysis highlighted the need for context-specific thresholds. These findings show the need for both antibody titre and avidity assessment in vaccine evaluations in endemic settings.

During a period of Omicron variant circulation, we estimated relative VE of COVID-19 mRNA booster vaccination versus primary two-dose series in an ongoing community cohort. Relative VE was 66% (95% CI: 46%, 79%) favoring the booster dose compared to primary series vaccination. Our results support current booster recommendations.