Vaccine exposure during pregnancy among privately and publicly insured women in the United States, 2016–2018

BackgroundVaccine use during pregnancy affects maternal and infant health. Many women do not receive vaccines recommended during pregnancy; conversely, inadvertent exposure to vaccines contraindicated or not recommended during pregnancy may occur. We assessed exposure to two recommended vaccines and two vaccines not recommended during pregnancy among privately and Medicaid-insured women in the United States.MethodsThis study includes a retrospective cohort of pregnancies in women aged 12–55 years resulting in live birth, spontaneous abortion, or stillbirth identified in the IBM® MarketScan® Commercial, Blue Health Intelligence® (BHI®) Commercial, and IBM MarketScan Multi-State Medicaid Databases from August 1, 2016, to December 31, 2018. Gestational age at vaccination was determined using a validated algorithm. We examined vaccines (1) recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) (tetanus, diphtheria, and acellular pertussis [Tdap]; inactivated influenza) and (2) not recommended (human papillomavirus [HPV]) or contraindicated (measles, mumps, and rubella [MMR]).ResultsWe identified 496,771 (MarketScan Commercial), 858,961 (BHI), and 289,573 (MarketScan Medicaid) pregnancies (approximately 75% aged 20–34 years). Across these three databases, 52.1%, 50.3%, and 31.3% of pregnancies, respectively, received Tdap, most often at a gestational age of 28 weeks, and influenza vaccination occurred in 32.1%, 30.8%, and 18.0% of pregnancies, respectively. HPV vaccination occurred in < 0.2% of pregnancies, mostly in the first trimester among women aged 12–19 years, and MMR was administered in < 0.1% of pregnancies. Use of other contraindicated vaccines per ACIP (e.g., varicella, live attenuated influenza) was rare.ConclusionMaternal vaccination with ACIP-recommended vaccines was suboptimal among privately and Medicaid-insured patients, with lower vaccination coverage among Medicaid-insured pregnancies than their privately insured counterparts. Inadvertent exposure to contraindicated vaccines during pregnancy was rare. This study evaluated only vaccinations reimbursed among insured populations and may have limited generalizability to uninsured populations.     

Maternity care provider acceptance of a future Group B Streptococcus vaccine – A qualitative study in three countries

IntroductionThere are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). When approved, GBS vaccines will be intended for administration to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its’ uptake in the population. Experience with prior maternal vaccines, e.g. influenza, Tdap and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women, and that provider recommendation is a key driver of vaccine uptake.MethodsThis study investigated attitudes of maternity care providers towards the introduction of a GBS vaccine in three countries (the United States (US), Ireland, and the Dominican Republic (DR)) with different GBS prevalence and prevention practices. Semi-structured interviews with maternity care providers were transcribed and coded for themes. The constant comparative method, and inductive theory building were used to develop conclusions.ResultsThirty-eight obstetricians, 18 general practitioners and 14 midwives participated. There was variability in provider attitudes towards a hypothetical GBS vaccine. Responses ranged from enthusiasm to doubts over the need for a vaccine. Attitudes were influenced by perceived additional benefits of a vaccine over current strategy and confidence in the safety of vaccines during pregnancy. Knowledge, experience and approaches to GBS prevention differed geographically and according to provider type, and influenced how participants assessed the risks and benefits of a GBS vaccine.ConclusionMaternity care providers are engaged in the topic of GBS management and there is opportunity to leverage attitudes and beliefs that will support a strong recommendation for a GBS vaccine. However, knowledge of GBS, and of the limitations of current prevention strategies vary among providers in different regions, and between different provider types. Targeted educational efforts with antenatal providers should focus on highlighting safety data the potential benefits of vaccination over current strategies.     

Motivational interviewing for maternal Immunizations: Intervention development

Background and ObjectiveVaccine uptake during pregnancy remains low. Our objectives were to describe 1) development and adaptation of a clinician communication training intervention for maternal immunizations and 2) obstetrics and gynecology (ob-gyn) clinician and staff perspectives on the intervention and fit for the prenatal care context.MethodsDesign of the Motivational Interviewing for Maternal Immunizations (MI4MI) intervention was based on similar communication training interventions for pediatric settings and included presumptive initiation of vaccine recommendations (“You’re due for two vaccines today”) combined with motivational interviewing (MI) for hesitant patients. Interviews and focus group discussions were conducted with ob-gyn clinicians and staff in five Colorado clinics including settings with obstetric physicians, certified nurse midwives (CNMs), and clinician-trainees. Participants were asked about adapting training to the ob-gyn setting and their implementation experiences. Feedback was incorporated through iterative changes to training components.ResultsInterview and focus group discussion results from participants before (n = 3), during (n = 11) and after (n = 25) implementation guided intervention development and adaptation. Three virtual, asynchronous training components were created: a video and two interactive modules. This virtual format was favored due to challenges attending group meetings; however, participants noted opportunities to practice skills through role-play were lacking. Training modules were adapted to include common challenging vaccine conversations and live-action videos. Participants liked interactive training components and use of adult learning strategies. Some participants initially resisted the presumptive approach but later found it useful after applying it in their practices. Overall, participants reported that MI4MI training fit well with the prenatal context and recommended more inclusion of non-clinician staff.ConclusionsMI4MI training was viewed as relevant and useful for ob-gyn clinicians and staff. Suggestions included making training more interactive, and including more complex scenarios and non-clinician staff.     

Systematic literature review of cross-protective effect of HPV vaccines based on data from randomized clinical trials and real-world evidence

BackgroundThe extent of cross-protection provided by currently licensed bivalent and quadrivalent HPV vaccines versus direct protection against HPV 31-, 33-, 45-, 52-, and 58-related disease is debated. A systematic literature review was conducted to establish the duration and magnitude of cross-protection in interventional and observational studies.MethodsPubMed and Embase databases were searched to identify randomized controlled trials (RCT) and observational studies published between 2008 and 2019 reporting on efficacy and effectiveness of HPV vaccines in women against non-vaccine types 31, 33, 45, 52, 58, and 6 and 11 (non-bivalent types). Key outcomes of interest were vaccine efficacy against 6- and 12-month persistent infection or genital lesions, and type-specific genital HPV prevalence or incidence. RCT data were analyzed for the according-to-protocol (bivalent vaccine) or negative-for-14-HPV-types (quadrivalent vaccine) efficacy cohorts.ResultsData from 23 RCTs and 33 observational studies evaluating cross-protection were extracted. RCTs assessed cross-protection in post-hoc analyses of small size subgroups. Among fully vaccinated, baseline HPV-naïve women, the bivalent vaccine showed statistically significant cross-protective efficacy, although with wide confidence intervals, against 6-month and 12-month persistent cervical infections and CIN2+ only consistently for HPV 31 and 45, with the highest effect observed for HPV 31 (range 64.6% [95% CI: 27.6 to 83.9] to 79.1% [97.7% CI: 27.6 to 95.9] for 6-month persistent infection; maximal follow-up 4.7 years). No cross-protection was shown in extended follow-up. The quadrivalent vaccine efficacy reached statistical significance for HPV 31 (46.2% [15.3–66.4]; follow-up: 3.6 years). Similarly, observational studies found consistently significant effectiveness only against HPV 31 and 45 with both vaccines.ConclusionsRCTs and observational studies show that cross-protection is inconsistent across non-vaccine HPV types and is largely driven by HPV 31 and 45. Furthermore, existing data suggest that it wanes over time; its long-term durability has not been established.     

Body mass index and vaccine responses following influenza vaccination during pregnancy

Background and AimsInfluenza vaccination is recommended by the World Health Organisation for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza infection. Various factors can influence vaccine immunogenicity, with obesity being one factor implicated in varied responses. This study aimed to investigate the impact of body mass index (BMI) on vaccine responses following influenza vaccination during pregnancy.MethodsPregnant women attending the Women’s and Children’s Hospital in South Australia during 2014–2016 were invited to participate. Participant’s clinical and demographic factors were recorded prior to administration of licensed seasonal influenza vaccination. Blood samples were collected before and one month post-vaccination to measure antibody responses by haemagglutination inhibition (HI) assay. Seroprotection was defined as a post-vaccination HI titre ≥ 1:40. Regression models assessed associations with failure to achieve seroprotective antibodies to H1, H3, and B influenza strains.ResultsA total of 96 women were enrolled in the study at a median gestation of 22 weeks with a BMI range of 18–49 kg/m². Paired sera samples were available for 90/96 (94%). Most pregnant women (72/90, 80%) demonstrated seroprotective antibody titres to all three influenza vaccine antigens (A(H1N1)pdm09, A(H3N2), B/Yamagata) following vaccination. Compared with women with BMI < 30 kg/m², those with high BMI were less likely to fail to achieve seroprotective antibodies, however this was not statistically significant (RR 0.42, 95% CI 0.11–1.68; p = 0.22). A greater proportion of women vaccinated during their second (47/53, 93%) or third trimester (18/25, 72%) demonstrated seroprotection to all three vaccine antigens following vaccination compared with women vaccinated during their first trimester (7/12, 58%).ConclusionHigh BMI did not impair seroprotection levels following influenza vaccination in pregnant women. Gestation at vaccination may be an important consideration for optimising vaccine protection for pregnant women and their newborns. Further assessment of first trimester influenza vaccine responses is warranted.     

Knowledge,attitudes, and practices regarding seasonal influenza vaccination during pregnancy in Costa Rica: A mixed-methods study

BackgroundInfluenza increases stillbirth risk, morbidity and mortality in pregnant women. Vaccination protects pregnant women against severe disease and indirectly protects their infants, but coverage among pregnant women remains low worldwide. We aimed to describe knowledge, attitudes, and practices (KAP) regarding seasonal influenza vaccination among postpartum women and prenatal care physicians in Costa Rica.MethodsWe conducted cross-sectional KAP surveys to women one to three days after childbirth at Costa Rican Social Security Fund maternity hospitals, and obstetricians and general practitioners who provided prenatal care in 2017. Principal components analysis, multiple imputation, and logistic regression were used to examine associations between influenza vaccination and demographics, prenatal care, and sources of information—separately for postpartum women and physicians. We also held two focus groups of six healthcare workers each to further describe vaccination KAP.ResultsWe surveyed 642 postpartum women and 146 physicians in maternity hospitals in five Costa Rican provinces of whom 85.5 % (95 % CI: 82.6 %-88.0 %) and 57.9 % (95 % CI: 49.6 %-65.7 %) were vaccinated for influenza, respectively. Factors associated with influenza vaccination for postpartum women included tetanus vaccination (aOR: 3.62, 95 % CI: 1.89–6.92); received vaccination recommendations from clinicians during prenatal check-ups (aOR: 3.39, 95 % CI: 2.06–5.59); had other children in household vaccinated for influenza (aOR: 2.25, 95 % CI: 1.08–4.68); and secondary/university education (aOR: 0.15–0.31) with no formal education as reference. For postpartum women, reasons for vaccination were perceived benefits for mother and infant, whereas not being offered vaccines was most cited for non-vaccination. Most prenatal care physicians recommended influenza vaccines during prenatal check-ups but believed vaccination causes flu-like symptoms.ConclusionVaccination campaigns and provisions of free vaccines effectively increased knowledge and coverage among women in Costa Rica. To improve access, women should be offered vaccines during prenatal care appointments. Educating healthcare workers about vaccine benefits for themselves and patients is needed to mitigate safety concerns.     

Immunogenicity,transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized,placebo-controlled trial

BackgroundPertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach.MethodsThis phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27–36 weeks’ gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded.Results687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5–19.2) for anti-filamentous hemagglutinin, 20.7 (15.9–26.9) for anti-pertactin and 8.5 (7.0–10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination.ConclusionsTdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease.Clinical Trial Registration. ClinicalTrials.gov: NCT02377349.     

Impact of media reports regarding influenza vaccine on obstetricians’ vaccination practices

BackgroundIn 2017, three media stories regarding influenza vaccine may have impacted obstetricians’ (OB) influenza vaccination practices: reports of reduced influenza vaccine effectiveness, a severe influenza season, and a possible increased risk of miscarriage among pregnant women receiving 2009 H1N1 vaccine in the 1st trimester who had received H1N1 vaccine the previous season (later disproven).ObjectiveDescribe OB’s: (1) awareness of; (2) attitudes and experiences related to; and (3) reported alterations in practice as a result of these reports.MethodsA survey among a nationally representative sample of OBs April to June 2018.ResultsResponse rate was 65% (302/468). 88% of OBs were “very aware” of the severe season, 74% of lower effectiveness, and 25% of the miscarriage study (47% “completely unaware” of miscarriage study). Among those aware, 58%, 57%, and 16% reported ≥10% of pregnant patients initiated discussions about the severe season, lower effectiveness, and miscarriage study, respectively. Most (83%) agreed reports about increased severity increased their enthusiasm for recommending influenza vaccine; fewer agreed reports about the miscarriage study (18%) and lower vaccine effectiveness (12%) decreased their enthusiasm for recommending influenza vaccine. Providers were more likely to initiate discussion with patients about increased severity of the season than the other reports. However, 35% agreed the miscarriage study reports increased their concerns about influenza vaccine safety; 18% (n = 48) reported changing the way they recommended influenza vaccine. Of those, 17 (6% of all respondents) reported not recommending influenza vaccine to women during the 1st trimester and 26 (10% of all respondents) recommended it but were willing to delay until the 2nd trimester.ConclusionsDuring a season in which media stories could have influenced OB influenza vaccination behaviors in different directions, reports underscoring importance of influenza vaccine may have had more impact on OBs’ recommendations than reports questioning vaccine safety or effectiveness.     

Impact of tetanus-diphtheria-acellular pertussis immunization during pregnancy on subsequent infant immunization seroresponses: follow-up from a large randomized placebo-controlled trial

BackgroundPertussis immunization during pregnancy results in high pertussis antibody concentrations in young infants but may interfere with infant immune responses to post-natal immunization.MethodsThis phase IV, multi-country, open-label study assessed the immunogenicity and safety of infant primary vaccination with DTaP-HepB-IPV/Hib and 13-valent pneumococcal conjugate vaccine (PCV13). Enrolled infants (6–14 weeks old) were born to mothers who were randomized to receive reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) during pregnancy (27^0/7–36^6/7 weeks’ gestation) with crossover immunization postpartum. All infants received 2 or 3 DTaP-HepB-IPV/Hib and PCV13 doses according to national schedules. Immunogenicity was assessed in infants pre- and 1 month post-primary vaccination. The primary objective was to assess seroprotection/vaccine response rates for DTaP-HepB-IPV/Hib antigens 1 month post-primary vaccination.Results601 infants (Tdap group: 296; control group: 305) were vaccinated. One month post-priming, seroprotection rates were 100% (diphtheria; tetanus), ≥98.5% (hepatitis B), ≥95.9% (polio) and ≥94.5% (Hib) in both groups. Vaccine response rates for pertussis antigens were significantly lower in infants whose mothers received pregnancy Tdap (37.5–77.1%) versus placebo (90.0–99.2%). Solicited and unsolicited adverse event rates were similar between groups. Serious adverse events occurred in 2.4% (Tdap group) and 5.6% (control group) of infants, none were vaccination-related.ConclusionsPertussis antibodies transferred during pregnancy may decrease the risk of pertussis infection in the first months of life but interfere with the infant’s ability to produce pertussis antibodies, the clinical significance of which remains unknown. Safety and reactogenicity results were consistent with previous experience.Clinical Trial Registration: ClinicalTrials.gov: NCT02422264.     

Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27–45 years of age compared to women 16–26 years of age: An open-label phase 3 study

BackgroundEfficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16–26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27–45 versus 16–26 years of age.MethodsThis international, open-label study (NCT03158220) was conducted in women 16–45 years of age. Participants (16–26 years, n = 570 and 27–45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study.ResultsAt month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27–45 years were compared to those in women 16–26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27–45 years to 16–26 years) was 0.60–0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27–45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16–26 years, and 85.2% and 24.1% of women 27–45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study.ConclusionsThe 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27–45 years compared with women 16–26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16–26 years to women 27–45 years of age.Clinical trial registration NCT03158220.     

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.     

Feasibility of age- and gestation-based routine universal influenza vaccines schedules for children aged 6 months − 2 years and pregnant women

BackgroundHong Kong’s seasonal influenza schedule follows the World Health Organization’s northern hemisphere vaccine composition recommendations but with year-round influenza activity there is the potential to implement routine age- and gestation-based schedules utilising both northern and southern hemisphere vaccines for children aged 6 months to 2 years and for pregnant women. This study assessed the potential feasibility of such schedules.MethodsA literature review was conducted and in-depth interviews with vaccine experts, policy makers and nurses were undertaken.ResultsThe following schedules were proposed and assessed for perceived feasibility: 1) a four-dose schedule in the first two years of life requiring an additional unscheduled clinic visit at 7 months; 2) a three-dose schedule excluding the 4-week booster after the first dose; 3) a two-dose schedule for pregnant women involving a dose at the booking visit and a dose with pertussis vaccine at 7 months gestation; and 4) a one-dose schedule at 7 months gestation.ConclusionsAge- and gestation-based routine influenza vaccination schedules are theoretically feasible for both young children and pregnant women. The three-dose paediatric and one-dose obstetric schedules were assessed in interviews with vaccine experts, policy makers and nurses to be most acceptable. Further clinical studies are required to determine whether such schedules are non-inferior to current seasonal-based schedules in terms of vaccine effectiveness and vaccine uptake.     

Survey of influenza vaccine knowledge,attitudes, and beliefs among pregnant women in the 2016–17 season

ObjectivesInfluenza vaccination coverage among pregnant women in the United States is suboptimal. We surveyed women who were pregnant during the 2016–17 influenza season to assess knowledge and attitudes regarding influenza vaccination.MethodsWe identified and sampled pregnant women to include approximately equal numbers of vaccinated and unvaccinated women from strata defined by vaccination status and trimester from four integrated health systems in the Vaccine Safety Datalink (VSD). Potential participants were contacted via mail and telephone to complete a standardized survey. Characteristics and responses of women vaccinated and unvaccinated during pregnancy were compared.ResultsThe survey was completed by 510 (48%) of 1062 contacted women; 500 were included in the analysis. Vaccine receipt while pregnant was associated with primigravida status (p = 0.02), college degree (p = 0.01), employment in health care (p < 0.01), and history of routine annual influenza vaccination (p < 0.01). Among 330 vaccinated women, the primary reasons for vaccination included protection of self and baby from influenza (n = 233, 71%), and medical professional recommendation (n = 46, 14%). Multiple reasons were given for nonvaccination, but concern about ‘negative effects’ was cited most often (n = 44, 29%). Vaccinated women were significantly more likely to believe that influenza vaccines are safe and effective, and to recognize the potential for harm from influenza infection. Nearly all women reported receiving at least one influenza vaccination recommendation from a healthcare provider.ConclusionsVaccinated pregnant women were more likely to receive routine annual influenza vaccine compared to those not vaccinated. Recommendations by obstetric providers should be supplemented with efforts to encourage women of childbearing age to receive annual vaccination.     

Pertussis and influenza immunisation coverage of pregnant women in New Zealand

BackgroundImmunisation is an important public health policy and measuring coverage is imperative to identify gaps and monitor trends. New Zealand (NZ), like many countries, does not routinely publish coverage of immunisations given during pregnancy. Therefore, this study examined pregnancy immunisation coverage of all pregnant NZ women between 2013 and 2018, and what factors affected uptake.MethodsA retrospective cohort study of pregnant women who delivered between 2013 and 2018 was undertaken using administrative datasets. Maternity and immunisation data were linked to determine coverage of pertussis and influenza vaccinations in pregnancy. Generalised estimating equations were used to estimate the odds of receiving a vaccination during pregnancy.ResultsFrom 2013 to 2018 data were available for 323,622 pregnant women, of whom 21.7% received maternal influenza immunisations and 25.7% maternal pertussis immunisations. Coverage for both vaccines increased over time, pertussis increased from 10.2% to 43.6% and influenza from 11.2% to 30.8%. The odds of being vaccinated, with either vaccine, during pregnancy increased with increasing age and decreasing deprivation. Compared to NZ European or Other women, Māori and Pacific women had lower odds of receiving a maternal pertussis (OR:0.55, 95% CI: 0.54, 0.57; OR:0.60, 95% CI: 0.58, 0.62, respectively) and influenza (OR: 0.69, 95% CI: 0.67, 0.71; OR:0.90, 95% CI: 0.87, 0.94, respectively) immunisations during pregnancy. Women were also more likely to be vaccinated against pertussis if they received antenatal care from a General Practitioner or Obstetrician compared to a Midwife. A similar pattern was seen for influenza vaccination.ConclusionGaps in maternal coverage for pertussis and influenza exist and work is needed to reduce immunisation inequities.     

Physician clinical decision support system prompts and administration of subsequent doses of HPV vaccine: A randomized clinical trial

BackgroundHPV vaccine is effective in preventing several cancers and anogenital warts, yet rates of HPV vaccination series completion in the United States are low. A primary reason identified by parents for vaccinating children against HPV is a health care provider’s recommendation. Although most clinicians embrace vaccine recommendations, they are not always carried out evenly and subsequent HPV vaccines are missed.MethodsUsing an electronic health records-based decision support system (CHICA) clinicians were randomized to either usual practice or to receive an automated reminder to recommend the 2nd or 3rd dose of HPV vaccine. The reminder was delivered to clinicians of all intervention group eligible adolescents who had already initiated the vaccine series. Logistic regression models with generalized estimating equations were used for data analysis.ResultsA total of 1285 clinical encounters were observed across 29 randomized pediatric providers over a 13-month time frame (50.7% control group, 49.3% intervention group). Overall, patients were 44.9% female, 59.4% Black, 22.1% Hispanic, and 48.8% were ages 11–12 yrs. Within the control group, 421 (64.7%) received a subsequent HPV vaccine, compared to 481 (75.9%) (OR: 1.72, (95% CI 1.35–2.19)). Adjusted analysis showed no difference between the groups (aOR 1.52 (95% CI 0.88–2.62)) or when examined by age (11-12yrs aOR 1.66, (95% CI 0.79–3.48)) and 13-17yrs (aOR 1.19, (95% CI 0.76–1.85)) or gender female (aOR 1.39 (95% CI 0.71–2.72)) and males (aOR 1.67 (95% CI 0.95–2.92)). When results were stratified by both age and gender, there was similarly no statistically significant effect between the two groups.ConclusionsAutomated physician reminders for subsequent 2nd and 3rd doses of HPV vaccination were used. Despite increased rates of vaccination in the intervention group, the differences did not reach the level of statistical significance. Future studies with multifaceted approaches may be needed to examine the efficacy of computer-based reminders.Clinical Trial Registration: NCT02558803, “HPV Vaccination: Evaluation of Reminder Prompts for Doses 2 & 3”.     

Systematic literature review of neutralizing antibody immune responses to non-vaccine targeted high-risk HPV types induced by the bivalent and the quadrivalent vaccines

IntroductionStudies on the cross-protective effect of HPV bivalent and quadrivalent vaccines demonstrated inconsistent findings against additional HPV types covered by the nonavalent vaccine. The objective of this study was to conduct a systematic literature review to assess the consistency and durability of the cross-protective neutralizing antibody immune responses of the currently licensed bivalent and quadrivalent vaccines to non-vaccine HPV types targeted by the nonavalent vaccine (HPV 6, 11, 31, 33, 45, 52, and 58).MethodsPubMed and EMBASE databases were searched from 2008 to 2019 to identify studies reporting antibody/immune response after vaccination with either the bivalent, quadrivalent, or nonavalent vaccine. Key outcomes were seroconversion, seropositivity or geometric mean titers against HPV types 6, 11, 31, 33, 45, 52, and 58.ResultsEighteen publications met inclusion criteria, reporting on 14 interventional and five observational studies. Across all studies, immune responses to non-vaccine high-risk HPV types after bivalent vaccination were higher than baseline or quadrivalent vaccine. Nonavalent vaccine elicited near total seroconversion to HPV types 31, 33, 45, 52, and 58, with seropositivity remaining near 100% up to 24 months post-dose 1. In contrast, bivalent and quadrivalent vaccination resulted in lower seroconversion levels for non-vaccine types, which waned over time.ConclusionsThe cross-protection antibody/immune response among participants having received all three doses of bivalent or quadrivalent vaccine is not comparable to the specific response elicited by HPV vaccine types. Even in cases where a statistically significant cross-reactive immunological response is reported, long-term data on the duration of the response beyond two years are very limited. Further, the lack of a standard for assays limits comparability of results between studies.     

The adjuvanted recombinant zoster vaccine co-administered with a tetanus,diphtheria and pertussis vaccine in adults aged ≥50 years: A randomized trial

BackgroundThis study evaluated immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) and the reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (Tdap) when co-administered in adults aged ≥50 years.MethodsIn this open label, multi-center study (NCT02052596), participants were randomized 1:1 to the Co-Administration group (RZV dose 1 and Tdap at Day 0 [D0], RZV dose 2 at Month 2 [M2]) or Control group (Tdap at D0, RZV dose 1 at M2, RZV dose 2 at M4). Co-primary objectives were evaluation of the vaccine response rate (VRR) to RZV in the Co-Administration group, and demonstration of non-inferiority of the humoral responses to RZV and Tdap in the Co-Administration compared to Control group. Reactogenicity and safety of RZV and Tdap were also assessed.ResultsVRR to RZV was 97.8% in the Co-Administration group. The non-inferiority criterion was met for the humoral response to RZV and for 4 Tdap antigens, but was not met for the Tdap antigen pertactin. Occurrences of solicited, unsolicited and serious adverse events, and potential immune-mediated diseases were similar between groups.ConclusionsCo-administration of RZV and Tdap did not interfere with the humoral immune response to RZV or 4 of the 5 Tdap antigens. No safety concerns were identified.     

Importance and value of adjuvanted influenza vaccine in the care of older adults from a European perspective – A systematic review of recently published literature on real-world data

BackgroundThere is an urgent need for improved influenza vaccines especially for older adults due to the presence of immunosenescence. It is therefore highly relevant to compare enhanced influenza vaccines with traditional influenza vaccines with respect to their effectiveness.ObjectiveTo compare vaccine efficacy and effectiveness of adjuvanted influenza vaccines (aTIV/aQIV) vs. non-adjuvanted standard-dose (TIV/QIV) and high-dose (TIV-HD/QIV-HD) influenza vaccines regarding influenza-related outcomes in older adults, complementing findings from the European Centre for Disease Prevention and Control (ECDC)’s systematic review of enhanced seasonal influenza vaccines from February 2020.MethodsA systematic literature search was conducted in Embase and MEDLINE to identify randomised controlled trials, observational studies and systematic reviews, published since ECDC’s systematic review (between 7 February 2020 and 6 September 2021). Included studies were appraised with either the Cochrane Risk of Bias tool, ROBINS-I or AMSTAR 2.ResultsEleven analyses from nine real-world evidence (RWE) studies comprising ～53 million participants and assessing the relative vaccine effectiveness (rVE) of aTIV vs. TIV, QIV and/or TIV-HD in adults aged ≥65 years over the 2006/07–2008/09 and 2011/12–2019/20 influenza seasons were identified. Nine analyses found that aTIV was significantly more effective than TIV and QIV in reducing influenza-related outcomes by clinical setting and suspected influenza outbreaks (rVE ranging from 7.5% to 25.6% for aTIV vs. TIV and 7.1% to 36.3% for aTIV vs. QIV). Seven analyses found similar effectiveness of aTIV vs. TIV-HD in reducing influenza-related medical encounters, inpatient stays and hospitalisations/emergency room visits. In three analyses, aTIV was significantly more effective than TIV-HD in reducing influenza-related medical encounters and office visits (rVE ranging from 6.6% to 16.6%). Risk of bias of identified studies was moderate to high.ConclusionsOur study suggests that both adjuvanted and high-dose vaccines are effective alternatives for vaccination programmes in older adults and preferable over conventional standard-dose vaccines.