Socioeconomic disadvantage and human papillomavirus (HPV) vaccination uptake

ImportanceDespite availability of safe and effective human papillomavirus (HPV) vaccines, vaccination uptake remains low in the U.S. Research examining the impact of neighborhood socioeconomic status on HPV vaccination may help target interventions.ObjectiveTo examine the association between area deprivation and HPV vaccine initiation and completion.Design, setting, participantsRetrospective cohort study of individuals aged 11–18 years residing in the upper Midwest region. Receipt of HPV vaccination was examined over a three-year follow-up period (01/01/2016–12/31/2018).Main outcomes and measuresOutcomes of interest were initiation and completion of HPV vaccination. Demographic data were collected from the Rochester Epidemiology Project (REP). Area-level socioeconomic disadvantage was measured by calculating an Area Deprivation Index (ADI) score for each person, a measure of socioeconomic disadvantage derived from American Community Survey data. Multivariable mixed effect Cox proportional hazards models were used to examine the association of ADI quartiles (Q1-Q4) with HPV vaccine series initiation and completion, given initiation.ResultsIndividuals residing in census block groups with higher deprivation had significantly lower likelihood of HPV vaccine initiation (Q2: HR = 0.91, 0.84–0.99 Q3: HR = 0.83, 0.76–0.90; Q4: HR = 0.84, 0.74–0.96) relative to those in the least-deprived block groups (Q1). Similarly, those living in block groups with higher deprivation had significantly lower likelihood of completion (Q2: HR = 0.91, 0.86–0.97; Q3: HR = 0.87, 0.81–0.94; Q4: HR = 0.82, 0.74–0.92) compared to individuals in the least-deprived block groups (Q1).Conclusions and relevanceLower probability of both HPV vaccine-series initiation and completion were observed in areas with greater deprivation. Our results can inform allocation of resources to increase HPV vaccination rates in our primary care practice and provide an example of leveraging public data to inform similar efforts across diverse health systems.     

Pre-implementation evaluation for an HPV vaccine provider communication intervention among primary care clinics

ObjectivesInterventions to improve health care provider communication about HPV vaccination can increase vaccine acceptance. Our objectives were to (1) identify clinics in locations with high HPV-associated cancer and low HPV-vaccination rates that would potentially benefit from dissemination of a proposed HPV Provider Communication intervention and (2) use qualitative interviews and a dissemination and implementation framework to assess readiness for change and fit of the HPV Provider Communication intervention to the context of these clinics.MethodsLocal HPV-associated cancer and HPV vaccination rates were assigned to Practice-Based Research Network clinics using data from the Colorado Central Cancer Registry, the Colorado Immunization Information System, and the American Community Survey. Staff from 38 clinics located in areas with high numbers of adolescents not up-to-date for HPV vaccine and high rates of HPV-associated cancers were recruited for qualitative interviews. Interview questions used the Promoting Action on Research Implementation in Health Services (PARIHS) conceptual framework and addressed the proposed intervention, current vaccination practices and prior quality improvement (QI) experience.ResultsTwenty-seven interviews were completed with clinicians, clinic managers, and other staff across 17 clinics (9 pediatric, 5 family medicine, 3 public/school-based health). Most clinics had some prior QI experience and there were few thematic differences between sites with more or less foundation for QI/immunization work. Participants were motivated to improve the health of their patients and valued both guidelines and local experience as important evidence to consider adopting an intervention. Interviewees were more interested in implementing the proposed intervention if it aligned with existing priorities and fit within clinic workflows. Facilitation needs included adequate time and external facilitation support for data tracking and analysis.ConclusionsQualitative interviews to understand clinic context and fit of an HPV Provider Communication intervention can inform implementation in settings with the highest potential for clinical impact.     

Disparities in COVID-19 vaccine uptake among health care workers

BackgroundCOVID-19 vaccine uptake by healthcare workers (HCWs) is critical to protect HCWs, the patients they care for, and the healthcare infrastructure. Our study aims to examine the actual COVID-19 vaccination rate among HCWs and identify risk factors associated with vaccine nonacceptance.Study Design and MethodsA retrospective analysis of COVID-19 vaccinations for HCWs at a large multi-site US academic medical center from 12/18/2020 through 05/04/2021. Comparisons between groups were performed using unpaired student t-test for continuous variables and the chi-square test for categorical variables. A logistic regression analysis was used to assess the associations between vaccine uptake and risk factor(s).ResultsOf the 65,270 HCWs included in our analysis, the overall vaccination rate was 78.6%. Male gender, older age, White and Asian race, and direct patient care were associated with higher vaccination rates (P <.0001). Significant differences were observed between different job categories. Physicians and advanced practice staff, and healthcare professionals were more likely to be vaccinated than nurses and support staff.ConclusionsOur data demonstrated higher initial vaccination rates among HCWs than the general population national average during the study period. We observed significant disparities among different high-risk HCWs groups, especially among different job categories, black HCWs and younger HCWs despite their high risk of contracting the infection. Interventions to address lower vaccination rate and vaccine hesitancy should be built with these disparities and differences in mind to create more targeted interventions.     

Timeliness and factors associated with rotavirus vaccine uptake among Australian Aboriginal and non-Aboriginal children: A record linkage cohort study

ObjectivesRotavirus vaccines (RV), included in Australia’s National Immunisation Program from mid-July 2007, are unique in strict time limits for administration. Here, we report on timeliness of RV uptake, compare cumulative RV coverage to age 12 months with DTPa, and assess factors associated with receipt of RV among Aboriginal and non-Aboriginal children.MethodsBirth records for 681,456 children born in two Australian states in 2007–2012 were probabilistically linked to national immunisation records. We assessed on-time coverage (defined as receipt of vaccine dose between 4 days prior to scheduled date and the recommended upper limit) for RV and compared this to diphtheria-tetanus-pertussis (DTPa) vaccine. Logistic regression modelling was used to assess independent determinants of receipt of RV.ResultsCompared to non-Aboriginal infants, on-time RV coverage was lower for all doses among Aboriginal infants. Post the upper age limit of RV dose2, DTPa dose2 coverage increased by 9–16% to ≥90%, whereas RV coverage remained around 77% (Aboriginal) and 85% (non-Aboriginal). Compared to first-born children, the adjusted odds of receiving ≥1 RV dose if born to a mother with ≥3 previous births was 0.30 (95%CI: 0.27–0.34) among Aboriginal, and 0.53 (95%CI: 0.51–0.55) among non-Aboriginal children. Prematurity (<33 weeks), low birthweight (<1500 g), maternal age <20 years, maternal smoking during pregnancy and living in a disadvantaged area were independently associated with decreased vaccine uptake.ConclusionsAboriginal children are at greater risk of rotavirus disease than non-Aboriginal children and delayed vaccine receipt is substantially higher. Although specific programs targeting groups at risk of delayed vaccination might improve RV coverage, relaxation of upper age restrictions is most readily implementable, and its overall risk-benefit should be evaluated.     

Exploring socio-demographic and geospatial variation in human papillomavirus vaccination uptake in Virginia

Significant variation in human papillomavirus (HPV) vaccine coverage exists across the United States. A closer look at state and region-specific coverage is necessary to identify potentially modifiable disparities. Using ArcGIS software, we identify geospatial variation in HPV vaccine coverage in the state of Virginia and examine the relationship between various socio-demographic indicators and HPV vaccination uptake. HPV vaccination rates among adolescents 11 to 17 years as of 07/01/2018 were retrieved at the zip-code level from the Virginia Immunization Information System and chloropleth maps produced. The ArcGIS Hot Spot Analysis tool identified spatial clusters of zip codes with high and low vaccination rates. Population characteristics and socioeconomic indicators were retrieved from the 2010 United States Census and compared between statistically significant clusters of higher or lower than expected vaccination rates. Regions with significantly lower initiation rates were less populated, less educated, and had a lower median household income (MHI) with higher rates of poverty and unemployment. Among male adolescents, these areas had a significantly lower density of primary care providers and smaller African American and Hispanic populations. In contrast, regions with significantly lower series completion were more populated and had a higher MHI, but there was no difference in provider density or minority population. Ultimately, regional socioeconomic indicators are significant predictors of HPV vaccination, but have contrasting implications for series initiation and completion. Targeted interventions and safety net programs have traditionally focused on the socioeconomically disadvantaged, however it is the more affluent communities that may be struggling with series completion.     

Anal human papillomavirus among men who have sex with men in three metropolitan cities in southern China: implications for HPV vaccination

IntroductionMen who have sex with men (MSM), especially those infected with human immunodeficiency virus (HIV), are at disproportionate risk for human papillomavirus (HPV) infection. Data about anal HPV prevalence among MSM in southern China are limited.MethodsMSM were recruited between January 1 and August 31, 2017 in three metropolitan cities: Guangzhou, Shenzhen and Wuxi. A self-completed tablet-based questionnaire was used to collect information about socio-demographic/sexual behavioral characteristics, history of sexually transmitted infections (STIs) and recreational drug use. An anal brush was used to collect exfoliated cells for HPV DNA testing and genotyping, and a blood sample was taken for HIV testing. Penile/anal warts were checked by a clinician.ResultsA total of 536 MSM were enrolled, including 39 HIV-positive and 497 HIV-negative individuals. Compared with HIV-negative MSM, prevalence of any HPV genotype (79.5% vs 46.7%), any high-risk genotype (64.1% vs 36.6%) and any nonavalent vaccine-preventable genotype (53.9% vs 31.6%) was significantly higher in HIV-positive MSM, with all P < 0.01. HIV infection (adjusted odds ratio [AOR], 4.28; 95% confidence interval [CI], 1.87–9.80), using recreational drugs (AOR, 1.87; 95% CI, 1.22–2.87), having ≥ 3 years of sexual experience (AOR, 1.52; 95% CI, 1.01–2.28), having ≥ 6 lifetime male partners (AOR, 1.92; 95% CI, 1.29–2.86), and engaging receptive anal intercourse (AOR, 2.30; 95% CI, 1.48–3.57) were associated with higher anal HPV prevalence. Any HPV prevalence increased with age, from 24.5% at < 20 years to 55.8% at ≥ 40 years.ConclusionsAnal HPV prevalence was high among MSM in southern China, significantly associated with HIV status and sexual experience. HPV prevalence increased with age among MSM. A targeted HPV vaccination program for teenage MSM might be necessary. Our findings will inform targeted HPV modelling among MSM in China.     

Prevalence of human papillomavirus (HPV)-vaccine types by race/ethnicity and sociodemographic factors in women with high-grade cervical intraepithelial neoplasia (CIN2/3/AIS), Alameda County,California, United States

We evaluated racial/ethnic differences in prevalence of oncogenic HPV types targeted by the quadrivalent HPV vaccine (16/18) and nonavalent HPV vaccine (31/33/45/52/58) in women diagnosed with CIN2/3/AIS after quadrivalent HPV vaccine introduction (2008–2015). Typing data from 1810 cervical tissue specimen from HPV-IMPACT (Alameda County, California, US), a population-based CIN2/3/AIS surveillance effort, were analyzed. Using log-binomial regression, we calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) comparing type prevalence by race/ethnicity, adjusted for health insurance, age, CIN2/3/AIS grade, and time period, overall and in the “early vaccine era” (2008–2011) and “later vaccine era” (2012–2015). Overall, oncogenic HPV16/18 prevalence was significantly lower among black (43%) and Hispanic (43%) women compared with white (52%) women (aPR (95% CI): 0.80 (0.70, 0.93) and 0.80 (0.70, 0.91), respectively). In 2008-2011, proportion of HPV16/18 detected was significantly lower in black (47%), Hispanic (46%), and Asian (42%) women compared to white (58%) women (aPR (95% CI): 0.80 (0.67, 0.96), 0.75 (0.63, 0.90), and 0.73 (0.58, 0.90), respectively). There were no significant differences in 2012-2015. Between the two eras, HPV16/18 prevalence declined in white (−11%), black (−9%), and Hispanic (−6%) women, and increased in Asian women (12%). Decreasing HPV 16/18 prevalence in CIN2/3/AIS lesions in white, black, and Hispanic women may suggest benefit from quadrivalent vaccination. In our unadjusted analysis of HPV31/33/45/52/58, prevalence did not differ significantly by race/ethnicity, but was significantly higher among Hispanic women (32%) compared to white women (27%) after adjustment (aPR (95%CI): 1.22 (1.02, 1.47). Prevalence was also non-significantly higher among black (32%) and Asian (33%) women. This analysis suggests that the nonavalent vaccine’s potential for impact against cervical precancers will not be lower in women of color compared to white women. These data underscore the importance of equitable vaccination in facilitating continued declines of vaccine-preventable HPV types among all women.     

Factors associated with US caregivers’ uptake of pediatric COVID-19 vaccine by race and ethnicity

ObjectivesTo assess differences in willingness to vaccinate children against COVID-19, and factors that may be associated with increased acceptance, among US caregivers of various racial and ethnic identities who presented with their child to the Emergency Department (ED) after emergency use authorization of vaccines for children ages 5–11.Study designA multicenter, cross-sectional survey of caregivers presenting to 11 pediatric EDs in the United States in November-December 2021. Caregivers were asked about their identified race and ethnicity and if they planned to vaccinate their child. We collected demographic data and inquired about caregiver concerns related to COVID-19. We compared responses by race/ethnicity. Multivariable logistic regression models served to determine factors that were independently associated with increased vaccine acceptance overall and among racial/ethnic groups.ResultsAmong 1916 caregivers responding, 54.67% planned to vaccinate their child against COVID-19. Large differences in acceptance were noted by race/ethnicity, with highest acceptance among Asian caregivers (61.1%) and those who did not specify a listed racial identity (61.1%); caregivers identifying as Black (44.7%) or Multi-racial (44.4%) had lower acceptance rates. Factors associated with intent to vaccinate differed by racial/ethnic group, and included caregiver COVID-19 vaccine receipt (all groups), caregiver concerns about COVID-19 (White caregivers), and having a trusted primary provider (Black caregivers).ConclusionsCaregiver intent to vaccinate children against COVID-19 varied by race/ethnicity, but race/ethnicity did not independently account for these differences. Caregiver COVID-19 vaccination status, concerns about COVID-19, and presence of a trusted primary provider are important in vaccination decisions.     

Effectiveness of recombinant zoster vaccine (RZV) in patients with inflammatory bowel disease

Background and AimsPatients with Inflammatory bowel disease (IBD) are at an increased risk of developing herpes zoster (HZ). The effectiveness of the recombinant zoster vaccine (RZV) in patients with IBD is unknown.MethodsIn this retrospective cohort study using Explorys (October 2017–April 2020; IBM Corporation, Somers, NY, USA), the effectiveness of RZV for the prevention of HZ in patients with IBD ≥ 50 years was compared to general population aged ≥ 50 years. Rates of de-novo HZ were compared between patients with IBD and the general population and stratified by number of RZV doses received. Results are presented as odds ratios (OR) with 95% confidence intervals (CI).ResultsThe overall proportion of IBD patients ≥ 50 years who received HZ vaccination with the live zoster vaccine (ZVL) or RZV was low (n = 11320, out of 112,200 IBD patients in the cohort). A total of 1670 patients received RZV. Receipt of the RZV resulted in a significantly lower rate of HZ in IBD patients (OR 0.36, 95% CI 0.23–0.56) compared to the general population (OR 0.74, 95% CI 0.59–0.92). However, despite vaccination, patients with IBD who received the RZV were still 3-times more likely to develop HZ during the study follow up period compared to the general population receiving the RZV (OR 3.06, 95% CI 1.87–5.02) and unvaccinated IBD patients were 6-times more likely to develop HZ compared to general population (OR 6.21, 95% CI 6.02–6.41).ConclusionThe recombinant zoster vaccine is effective in reducing the risk of HZ in patients with IBD compared to the general population. During our follow up period, patients with IBD, however, still remain at an increased risk for HZ despite vaccination.     

Influenza virus vaccine compliance among pregnant women during the COVID-19 pandemic (pre-vaccine era) in Israel and future intention to uptake BNT162b2 mRNA COVID-19 vaccine

The influenza virus vaccine, used worldwide as an annual preventive measure, is especially recommended for at-risk populations. Older adults and pregnant women are therefore offered the flu shot free of charge in Israel. The Israel Ministry of Health’s rationale for giving the influenza vaccine to pregnant women is to avoid serious complications that could harm both mother and foetus. In Israel, the winter of 2020/2021 was marked by a third surge of COVID-19, raising the risk of contracting the SARS-CoV-2 virus and the level of fear among the population. The influenza vaccine protects individuals from the flu and thus helps prevent an additional burden on medical centres treating COVID-19 patients. The aim of the present study was to assess compliance of pregnant and postpartum women to influenza vaccine uptake during winter 20/21 period. A survey questionnaire was distributed to examine factors predicting women’s attitudes toward the influenza vaccine. Questionnaire items based on the Heath Belief Model examined participants’ perceptions regarding influenza and the vaccine. The questionnaire also evaluated participants’ hypothetical willingness to get immunized with the Pfizer COVID-19 vaccine upon its arrival in Israel. The results showed a higher prevalence of influenza vaccine uptake among Jewish women than Arab women, while level of trust in healthcare providers was stronger among Arab participants than among Jewish participants. The findings indicate that the pregnant and postpartum community needs better information dissemination and education regarding the importance of the influenza vaccine. Decisions regarding uptake of the COVID-19 vaccine upon future availability were found to be unrelated to influenza vaccine perceptions. The results call for raising public awareness regarding influenza immunization in addition to offering the vaccine at routine pregnancy follow-up appointments.     

Prevalence,capsular types,antimicrobial resistance and risk factors associated with pneumococcal carriage among children after long-term 10-valent pneumococcal conjugate vaccine use in Brazil

BackgroundThe 10-valent pneumococcal conjugate vaccine (PCV10) was introduced for childhood vaccination in Brazil’s National Immunization Program in 2010. After nine years of PCV10 use, we investigated the carriage prevalence, capsular types, antimicrobial resistance and risk factors among children living in Niterói city, RJ, Brazil.MethodsBetween September and December 2019, we conducted a cross-sectional study and recruited children under 6 years of age. Antimicrobial susceptibility was evaluated by the disk-diffusion method and MICs to beta-lactams and macrolides were determined by E-test®. Capsular types were deduced by multiplex PCR. Logistic regression was used to predict risk factors for pneumococcal carriage.ResultsSeventy-five (17.4%) of the 430 children were pneumococcal carriers. The most frequent capsular types were 6C/D (14.7%), 11A/D (13.3%), and 23B (9.3%). PCV10 serotypes represented 5.3%. All isolates were susceptible to levofloxacin, linezolid, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) made up 37.3%, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 μg/ml and 0.064–4.0 μg/ml, respectively. Of the 19 (25.3%) erythromycin-resistant (ERY-R) isolates (macrolide MICs of 6 to >256 μg/ml), most had the cMLS_B phenotype (84.2%) and carried the erm(B) gene (73.7%). We detected 17 (22.6%) multidrug-resistant (MDR) isolates, strongly associated with serotype 6C/D. Presence of any symptoms, chronic diseases, childcare center attendance, living with young siblings, slum residence, and unstable income were predictors of pneumococcal carriage.ConclusionsLong-term universal childhood use of PCV10 has nearly eliminated carriage with PCV10 serotypes, but the high frequency of MDR isolates, especially associated with serotype 6C/D, remains a concern. Replacing PCV10 with PCV13 should reduce the proportion of ERY-R isolates and PNSP by at least 14% and 18%, respectively.     

Effect of provider recommendation style on the length of adolescent vaccine discussions

ObjectiveTo determine whether providers’ vaccine recommendation style affects length of the adolescent vaccine discussions.MethodsWe analyzed vaccine discussions using audio-recordings of clinical encounters where adolescents were eligible for HPV vaccines ± meningococcal vaccines. We measured length of vaccine discussions, the provider’s use of an “indicated” (vaccination due at visit) or “elective” (vaccination is optional) recommendation style, and vaccine receipt. Parent and child demographics, parental vaccination intentions, and parental satisfaction with vaccine discussion were collected from pre- and post-visit surveys. We used linear and logit regressions with random effects to estimate recommendation style’s association with discussion length and with vaccine receipt, respectively.ResultsWe analyzed 106 vaccine discussions (82 HPV; 24 meningococcal) across 82 clinical encounters and 43 providers. Vaccine discussions were longer when providers presented vaccination as elective versus indicated (140 vs. 74 s; p-value < 0.001). Controlling for vaccine type, parental vaccination intent, and patient characteristics, an elective style was associated with 41 seconds longer vaccine discussion (p-value < 0.05). Providers used the indicated style more frequently with the meningococcal vaccine than with the HPV vaccine (96% vs. 72%; p-value < 0.05). Parents’ odds of vaccinating were 9.3 times higher following an indicated versus an elective presentation (p-value < 0.05). Vaccine discussion length and presentation style were not associated with parental satisfaction.ConclusionsOur results suggest that using an indicated recommendation improves vaccine discussions’ efficiency and effectiveness, but this style is used more often with meningococcal than HPV vaccines. Increasing providers’ use of indicated styles for HPV vaccines has the potential to increase vaccination rates and save time during medical visits.     

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.     

Individual factors influencing COVID-19 vaccine acceptance in between and during pandemic waves (July–December 2020)

BackgroundA year after the start of the COVID-19 outbreak, the global rollout of vaccines gives us hope of ending the pandemic. Lack of vaccine confidence, however, poses a threat to vaccination campaigns. This study aims at identifying individuals’ characteristics that explain vaccine willingness in Flanders (Belgium), while also describing trends over time (July–December 2020).MethodsThe analysis included data of 10 survey waves of the Great Corona Survey, a large-scale online survey that was open to the general public and had 17,722–32,219 respondents per wave. Uni- and multivariable general additive models were fitted to associate vaccine willingness with socio-demographic and behavioral variables, while correcting for temporal and geographical variability.ResultsWe found 84.2% of the respondents willing to be vaccinated, i.e., respondents answering that they were definitely (61.2%) or probably (23.0%) willing to get a COVID-19 vaccine, while 9.8% indicated maybe, 3.9% probably not and 2.2% definitely not. In Flanders, vaccine willingness was highest in July 2020 (90.0%), decreased over the summer period to 80.2% and started to increase again from late September, reaching 85.9% at the end of December 2020. Vaccine willingness was significantly associated with respondents’ characteristics: previous survey participation, age, gender, province, educational attainment, household size, financial situation, employment sector, underlying medical conditions, mental well-being, government trust, knowing someone with severe COVID-19 symptoms and compliance with restrictive measures. These variables could explain much, but not all, variation in vaccine willingness.ConclusionsBoth the timing and location of data collection influence vaccine willingness results, emphasizing that comparing data from different regions, countries and/or timepoints should be done with caution. To maximize COVID-19 vaccination coverage, vaccination campaigns should focus on (a combination of) subpopulations: aged 31–50, females, low educational attainment, large households, difficult financial situation, low mental well-being and labourers, unemployed and self-employed citizens.     

Efficacy of quadrivalent human papillomavirus vaccine against persistent infection and genital disease in Chinese women: A randomized,placebo-controlled trial with 78-month follow-up

BackgroundA quadrivalent human papillomavirus vaccine (qHPV; HPV6/11/16/18) has demonstrated efficacy and effectiveness worldwide. We report qHPV vaccine efficacy for up to 6.5 years after first administration among Chinese women 20–45 years of age.MethodsIn this randomized, double-blind, placebo-controlled, multicenter, Phase 3 study (NCT00834106), women were randomized 1:1 to receive 3 doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). Endo-ecto-cervical and external genital swabs were collected for HPV testing and gynecologic examinations, and cervical cytology testing were performed at Day 1 and Months 7, 12, 18, 24, 30, 42, 54, 66, and 78. Any abnormality in cytology testing would trigger colposcopy examination and cervical biopsy, if necessary. Efficacy against genital disease, persistent infection, and the composite endpoint was assessed. Primary efficacy analyses were conducted in the per-protocol efficacy (PPE) population.ResultsOf 3006 participants randomized, 2759 (91.8%) and 2374 (79%) completed the Month 30 and Month 78 visits, respectively. At Month 78, efficacy among women aged 20–45 years was 100% (95% CI: 32.3, 100; 0 vs 7 cases) and 100% (95% CI: 70.9, 100; 0 vs 14 cases) against HPV16/18-related cervical intraepithelial neoplasia Grade 2 or 3, adenocarcinoma in situ, and cervical cancer (CIN 2+) and HPV6/11/16/18-related CIN 1+, respectively, in the PPE population. The efficacy against cervical 6-month and 12-month persistent infection was 91.6% (95% CI: 66.0, 99.0) and 97.5% (95% CI: 85.1, 99.9) at Month 30 and Month 78, respectively, in the PPE population. The vaccine also reduced the rate of cervical cytology abnormalities associated with HPV6/11/16/18, with an efficacy of 94.0% (95% CI: 81.5, 98.8). The vaccine was generally well tolerated (reported separately).ConclusionThe qHPV vaccine is efficacious against endpoints of persistent infection and genital precancerous lesions in Chinese women aged 20–45 years.     

Long-term immunogenicity and safety of the hepatitis B vaccine HepB-CpG (HEPLISAV-B) compared with HepB-Eng (Engerix-B) in adults with chronic kidney disease

BackgroundHepatitis B virus (HBV) infection remains a significant global burden, especially for patients with chronic kidney disease (CKD) receiving hemodialysis. Three doses of HepB–CpG (HEPLISAV-B® vaccine) induced a superior immune response compared with 4 double doses of HepB–Eng (Engerix-B®) in a phase 3 trial (HBV-17) in adults with CKD. Here we report the long-term immunogenicity and safety of HepB-CpG and HepB–Eng in eligible participants of HBV-17 who enrolled in this optional 34-month follow-up trial (HBV-19).MethodsHBV-19 is a multicenter, open-label, phase 3b trial of adults with CKD who previously received a complete series of HepB-CpG or HepB-Eng in the HBV-17 trial. Participants were assigned to seroprotection categories at enrollment on the basis of their antibody response to hepatitis B surface antigen (anti-HBs) in HBV-17. The objective was to evaluate the durability of seroprotection (defined as an anti-HBs concentration ≥ 10 mIU/mL) induced by HepB-CpG and HepB-Eng. Participants whose anti-HBs concentration was below 10 mIU/mL received additional HepB-CpG or HepB-Eng doses.Results147 participants were enrolled; 66.7 % were men, median age was 65.0 years, and 83.7 % were white. The durability of seroprotection in participants with CKD was similar in those who received HepB-CpG and those who received HepB-Eng. Antibody concentrations ≥ 100 mIU/mL persisted for longer in HepB-CpG than HepB-Eng recipients, among those with anti-HBs ≥ 100 mIU/mL post vaccination. The geometric mean anti-HBs concentration in the HepB-CpG group was significantly higher than in the HepB-Eng group over time (P ≤ 0.0001). The safety profiles were similar between the vaccine groups.ConclusionsDue to the higher antibody levels induced by HepB-CpG in participants with CKD, seroprotection against HBV may be expected to persist longer than that induced by HepB-Eng. ClinicalTrials.gov: NCT01282762.     

A randomized phase 3 trial of the immunogenicity and safety of coadministration of a live-attenuated tetravalent dengue vaccine (TAK-003) and an inactivated hepatitis a (HAV) virus vaccine in a dengue non-endemic country

BackgroundVaccination against hepatitis A virus (HAV) is largely recommended for travelers worldwide. Concurrent dengue and HAV vaccination may be desired in parallel for travelers to countries where both diseases are endemic. This randomized, observer-blind, phase 3 trial evaluated coadministration of HAV vaccine with tetravalent dengue vaccine (TAK-003) in healthy adults aged 18–60 years living in the UK.MethodsParticipants were randomized (1:1:1) to receive HAV vaccine and placebo on Day 1, and placebo on Day 90 (Group 1), TAK-003 and placebo on Day 1, and TAK-003 on Day 90 (Group 2), or TAK-003 and HAV vaccine on Day 1, and TAK-003 on Day 90 (Group 3). The primary objective was non-inferiority of HAV seroprotection rate (anti-HAV ≥ 12.5 mIU/mL) in Group 3 versus Group 1, one month post-first vaccination (Day 30) in HAV-naïve and dengue-naïve participants. Sensitivity analyses were performed on combinations of baseline HAV and dengue serostatus. Secondary objectives included dengue seropositivity one month post-second vaccination (Day 120), HAV geometric mean concentrations (GMCs), and safety.Results900 participants were randomized. On Day 30, HAV seroprotection rates were non-inferior following coadministration of HAV and TAK-003 (Group 3: 98.7 %) to HAV administration alone (Group 1: 97.1 %; difference: ?1.68, 95 % CI: ?8.91 to 4.28). Sensitivity analyses including participants who were neither HAV-naïve nor DENV-naïve at baseline supported this finding. Anti-HAV GMCs on Day 30 were 82.1 (95 % CI: 62.9–107.1) mIU/mL in Group 1 and 93.0 (76.1–113.6) mIU/mL in Group 3. By Day 120, 90.9–96.8 % of TAK-003 recipients were seropositive (neutralizing antibody titer > 10) to all four dengue serotypes. Coadministration of HAV vaccine and TAK-003 was well tolerated, with no important safety risks identified.ConclusionImmune responses following coadministration of HAV vaccine and TAK-003 were non-inferior to administration of HAV vaccine alone. The results support the coadministration of HAV vaccine and TAK-003 with no adverse impact on immunogenicity, safety, and reactogenicity of either vaccine.ClinicalTrials.gov registration: NCT03525119.