A complementary approach to the vaccination promotion continuum: An immunization-specific motivational-interview training for nurses

AimTo develop and validate immunization-specific motivational-interview (MI) training for immunization nurses.BackgroundWe previously demonstrated that a MI-based intervention on immunisation, performed during postpartum by MI-trained healthcare workers at the hospital maternity ward, reduced parental vaccine hesitancy (VH) and increased vaccine coverage of their children. In this study, we propose immunization-specific MI training for immunization nurses. Together, MI-based training and interventions provide complementary approaches to existing strategies along the vaccination promotion continuum.DesignMultiple pretest/posttest design with questionnaires self-administered before and after each training days (4 time points).MethodsWe developed an in-person immunization-specific MI-training workshop for immunization nurses, held on two days three months apart, with 7 h of MI-training dispensed on day 1, and 4 h on day 2. The self-administered Motivational Interviewing Skills in Immunization (MISI) questionnaire was used at four time points (before and after each of the 2 training days) to evaluate three core aspects of participant MI training: (1) MI-knowledge acquisition; (2) MI-skills application and (3) self-rated self-confidence in applying MI knowledge and skills in vaccination clinical practice. Between November 2016 to December 2017, 34 immunization nurses enrolled in our MI-training workshops.ResultsThe immunization-specific MI-training improved the three core areas evaluated in participants i.e. MI-knowledge acquisition, MI-skills application, and self-rated self-confidence in applying these in vaccination clinical practice.ConclusionsOur immunization-specific MI-training enabled immunization nurses to significantly improve MI knowledge, skills and self-confidence in applying MI in the clinic. These results, taken together with those on the MI-based intervention for parents that we previously reported, support the notion of proposing validated immunization-specific MI training for immunization nurses in order to curb parental VH.ImpactImmunization-specific MI-training would be easily amenable for the training of other health professionals in the field of immunization to help promote vaccination and curb parental VH.     

Patient and clinician factors associated with uptake of the human papillomavirus (HPV) vaccine among adolescent patients of a primary care network

BackgroundHuman papillomavirus (HPV) vaccination rates for adolescents remain relatively low. The purpose of this study is to examine patient and clinician factors associated with HPV vaccination among patients, ages 11–17, of a large community-based primary care network.MethodsElectronic health records and administrative data from a large primary care network from January 2017 – June 2018 for patients ages 11–17 (n = 10,682) and the 198 primary care clinicians that saw them were analyzed. Mixed effects logistic regression models examined the association of patient and clinician factors with HPV vaccine uptake.ResultsMost patients (63.0%) had at least one dose of the HPV vaccine, and 37.7% were up to date. In adjusted analyses, patients who received the tetanus, diphtheria, and pertussis (Tdap) vaccine (OR = 2.8, 95% CI: 2.1–3.9) compared to those who did not receive the vaccine and patients with five or more medical visits (OR = 1.9, 95% CI: 1.6–2.2) had the greatest odds of being up to date with the HPV vaccine series. Compared to White patients, African American/Black (OR = 0.8, 95% CI: 0.6 – 1.0) and Alaskan Native/American Indian (OR = 0.5, 95% CI: 0.3–0.9) patients were less likely to be up to date. Boys were also less likely to be up to date with the HPV vaccine series compared to girls (OR = 0.7, 95% CI: 0.7–0.8). Additionally, patients with family/general practice primary care clinicians were less likely to have their patients up to date than those with pediatricians (OR = 0.8, 95% CI: 0.6 – 1.0).ConclusionHPV vaccine uptake varied by patient characteristics, heath care utilization and primary care clinician specialty. These findings may inform future evidence-based interventions aimed at increasing HPV vaccine uptake among adolescents by targeting patient sub-groups and reducing missed opportunities for vaccination.     

Motivational interviewing and vaccine acceptance in children: The MOTIVE study

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

Effectiveness of a multimodal intervention to increase vaccination in obstetrics/gynecology settings

ObjectiveTo test the effectiveness of a multimodal intervention in obstetrics/gynecology (ob-gyn) clinics to increase uptake of influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines in pregnant women and these vaccines plus human papillomavirus (HPV) vaccine in non-pregnant women.MethodsA cluster randomized controlled trial among 9 private ob-gyn practices in Colorado from 9/2011 to 5/2014. The intervention consisted of: designation of immunization champions, staff/provider trainings, assistance with vaccine purchasing/management, identification of eligible patients, standing order implementation, chart review/feedback, and patient education materials. Control practices continued usual care. Primary outcomes were receipt of influenza and Tdap vaccines among pregnant women and these vaccines plus HPV vaccine among non-pregnant women, comparing a Baseline period (Year 0/Year 1) to Year 2, intervention versus control. With an estimated sample size of 32,590 per arm, there would be >80% power to detect a 10% difference between groups.ResultsIn the Baseline period, 27% of pregnant women in both intervention and control practices received influenza vaccine. In Year 2, 29% of pregnant women in intervention practices received influenza vaccine versus 41% in control practices. In the Baseline period, 18% of pregnant women in intervention practices received Tdap vaccine versus 22% in control practices. Both intervention and control practices increased to 51% in Year 2, representing an increase of 33% for intervention practices and 29% for control practices, consistent with a change in Tdap recommendations. Relatively few HPV, influenza or Tdap vaccines (≤6% of eligible patients) were given to non-pregnant patients in either intervention or control practices at any time during the study.ConclusionIn this cluster randomized trial designed to increase vaccination uptake, both intervention and control practices showed improved vaccination of pregnant but not non-pregnant patients. Future work should focus on tailoring evidence-based immunization practices or developing new approaches to specifically fit busy ob-gyn offices.     

Safety and immunogenicity of NVX-CoV2373 (TAK-019) vaccine in healthy Japanese adults: Interim report of a phase I/II randomized controlled trial

BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110.     

Efficacy and safety of the BNT162b2 mRNA COVID-19 vaccine in participants with a history of cancer: subgroup analysis of a global phase 3 randomized clinical trial

IntroductionIndividuals with an underlying malignancy have high risk of poor COVID-19 outcomes. In clinical trials, COVID-19 vaccines were safe and efficacious against infection, hospitalization, and death, but most trials excluded participants with cancer. We report results from participants with a history of past or active neoplasm (malignant or benign/unknown) and up to 6 months’ follow-up post-dose 2 from the placebo-controlled, observer-blinded trial of the 2-dose BNT162b2 mRNA COVID-19 vaccine.Patients and methodsBetween July 2020–January 2021, 46,429 participants aged ≥ 12 years were randomized at 152 sites in 6 countries. Healthy participants with pre-existing stable neoplasm could participate; those receiving immunosuppressive therapy were excluded. Data are reported for participants, aged ≥ 16 years for safety and ≥ 12 years for efficacy, who had any history of neoplasm at baseline (data cut-off: March 13, 2021). Adverse-event (AE) data are controlled for follow-up time before unblinding and reported as incidence rates (IRs) per 100 person-years follow-up.ResultsAt baseline, 3813 participants had a history of neoplasm; most common malignancies were breast (n = 460), prostate (n = 362), and melanoma (n = 223). Four BNT162b2 and 71 placebo recipients developed COVID-19 from 7 days post-dose 2; vaccine efficacy was 94.4% (95% CI: 85.2, 98.5) after up to 6 months’ follow-up post-dose 2. This compares favorably with vaccine efficacy of 91.1% in the overall trial population after the same follow-up. AEs were reported at IRs of 95.4 (BNT162b2) and 48.3 (placebo) per 100 person-years. Most common AEs were reactogenicity events (injection-site pain, fatigue, pyrexia). Three BNT162b2 and 1 placebo recipients withdrew because of vaccine-related AEs. No vaccine-related deaths were reported.ConclusionIn participants with past or active neoplasms, BNT162b2 vaccine has a similar efficacy and safety profile as in the overall trial population. These results can inform BNT162b2 use during the COVID-19 pandemic and future trials in participants with cancer.Clinical trial number: NCT04368728.     

One year safety and immunogenicity of AZD1222 (ChAdOx1 nCoV-19): Final analysis of a randomized,placebo-controlled phase 1/2 trial in Japan

BackgroundLong duration trial data for two-dose COVID-19 vaccines primary series’ are uncommon due to unblinding and additional doses. We report one-year follow-up results from a phase 1/2 trial of AZD1222 (ChAdOx1 nCoV-19) in Japan.MethodsAdults (n = 256) seronegative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were stratified by age, 18–55 (n = 128), 56–69 (n = 86) and ≥70-year-old (n = 42), and randomized 3:1 to AZD1222 or placebo. Safety, immunogenicity, and exploratory efficacy data were collected until study Day 365.ResultsSafety was consistent with previous reports. In AZD1222 vaccinees, humoral responses against SARS-CoV-2 steadily declined over time. By Day 365, anti-SARS-CoV-2 spike-binding (spike) and receptor-binding domain (RBD) mean antibody titers remained above Day 15 levels and pseudovirus neutralizing antibodies were undetectable in many participants.ConclusionsAZD1222 is immunogenic and well tolerated in Japanese adults. Expected waning in anti-SARS-CoV-2 humoral responses was observed; spike and RBD antibody titers remained elevated. (ClinicalTrials.gov: NCT04568031).     

The impact of immunomodulating treatment on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases compared to healthy controls. A Swedish nationwide study (COVID19-REUMA)

ObjectivesTo elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs).MethodsAntibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2–12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins.ResultsPatients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21–40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2–12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001).ConclusionsOlder individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.     

Developing communication tools on rotavirus vaccination to support family paediatricians in Italy

BackgroundUniversal rotavirus (RV) vaccination for newborns was introduced in Italy in 2018, but national vaccination coverage is still suboptimal. Effective communication between the family paediatrician (FP) and parents/caregivers is essential to promote vaccination acceptance. This project aimed to support FPs in communicating RV vaccination to parents/caregivers through the development and implementation of demonstrative videos and training modules.MethodsA working group composed of two FPs, two communication professionals, a medical expert from GSK and a clinical psychologist, was formed to establish the key scientific information to be communicated to parents/caregivers and develop the demonstrative videos. Four videos depicting four communication styles (I to IV) were developed based on the Social Styles Theory. Thirty FPs were then asked to pilot test the videos and provide feedback. In addition, two training modules with scientific information were developed to learn how to respond to parents’/caregivers’ objections.ResultsA total of 23 FPs provided feedback after using one or more videos at least five times. Twenty FPs (87.0 %) used mostly-one style, and most (60.0 %) used Style IV. Overall, the feedback was positive, as the majority of FPs (82.6 %, n = 19/23) indicated that the proposed videos were ‘useful’ or ‘extremely useful’ for introducing the RV vaccination to parents/caregivers in their actual practice. Based on this feedback, shorter versions of each video were also produced, and two training modules were developed to support FPs in responding to parental objections. Most FPs 75 % (n = 9/12) found Module 1 ‘very useful’, and all found Module 2 ‘very useful’ (100 %, n = 12/12).ConclusionsThe communication tools developed were well appreciated by the FPs and are expected to support FPs in communicating RV vaccination thereby increasing its coverage. Practicing RV communication may also prove beneficial for FPs to communicate other critical topics to parents/caregivers.     

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

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

Bacille Calmette-Guérin vaccination at birth and differential white blood cell count in infancy. A randomised clinical trial

BackgroundThe Bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) may have beneficial non-specific effects (NSEs) beyond the protection against TB. This may be related to modifications of the innate immune system. We investigated the effect of BCG at birth on differential white blood cell (WBC) count in healthy, Danish infants.MethodThe Danish Calmette Study randomised newborns to BCG at birth (Danish strain 1331, Statens Serum Institut) or no intervention. A sub-group of infants had blood samples collected 4 days after randomisation (n = 161), and at age 3 months (n = 152) and 13 months (n = 300). We evaluated the effect of BCG on WBC differential count (total leucocytes, lymphocytes, monocytes, eosinophil, neutrophil and basophil granulocytes (10⁹ cells/L)) measured in peripheral blood.ResultsOverall, we found no effect of BCG on differential WBC counts at any time point.ConclusionBCG at birth did not affect WBC count in our cohort of healthy, Danish infants.     

Immunogenicity and safety of a single booster dose of NVX-CoV2373 (TAK-019) in healthy Japanese adults who had previously received a primary series of COVID-19 mRNA vaccine: Primary analysis report of a phase 3 open-label trial

BackgroundWe evaluated the immunogenicity and safety of a booster dose of NVX-CoV2373 in Japanese adults who had completed a primary series of COVID-19 mRNA vaccine 6–12 months previously.MethodsThis single-arm, open-label, phase 3 study, conducted at two Japanese centres, enrolled healthy adults ≥ 20 years old. Participants received a booster dose of NVX-CoV2373. The primary immunogenicity endpoint was non-inferiority (lower limit of the 95 % confidence interval [CI] ≥ 0.67) of the geometric mean titre (GMT) ratio of titres of serum neutralizing antibodies (nAbs) against the SARS-CoV-2 ancestral strain 14 days after booster vaccination (day 15) in this study, compared with those 14 days after the second primary NVX-CoV2373 vaccination (day 36) in the TAK-019-1501 study (NCT04712110). Primary safety endpoints included local and systemic solicited adverse events (AEs) up to day 7 and unsolicited AEs up to day 28.ResultsBetween 15 April 2022 and 10 May 2022, 155 participants were screened and 150, stratified by age (20–64 years old [n = 135] or ≥ 65 years old [n = 15]), received an NVX-CoV2373 booster dose. The GMT ratio between titres of serum nAbs against the SARS-CoV-2 ancestral strain on day 15 in this study and those on day 36 in the TAK-019-1501 study was 1.18 (95 % CI, 0.95–1.47), meeting the non-inferiority criterion. Following vaccination, the proportion of participants who reported local and systemic solicited AEs up to day 7 was 74.0 % and 48.0 %, respectively. The most common local and systemic solicited AEs were tenderness (102 participants [68.0 %]) and malaise (39 participants [26.0 %]), respectively. Seven participants (4.7 %) reported unsolicited AEs between vaccination and day 28; all were severity grade ≤ 2.DiscussionA single heterologous NVX-CoV2373 booster induced rapid and robust anti-SARS-CoV-2 immune responses, addressing waning immunity in healthy Japanese adults, and had an acceptable safety profile.ClinicalTrials.gov identifier: NCT05299359.     

Variable anti-HBs antibody titers in vaccinated birth cohorts – A cross-sectional population-based study

BackgroundAfter the introduction of hepatitis B (HB) vaccination in 1995 in newborns, two catch-up campaigns targeted unvaccinated 9 year old in 2000–2003 (born 1991–1994) and the 18 year old in 2004–2008 (born 1986–1990), resulting in several birth-cohorts. Our objective was to assess the anti-HBs titers in each birth-cohort.MethodsWe included all outpatients (78.5%) and hospitalized patients with measured anti-HBs antibody titers in the Teaching Hospital of Infectious Diseases, Cluj-Napoca, Romania, during April 2014 – December 2018 (without HB history). We compared the anti-HBs titers in all birth-cohorts using the Lexis surfaces (titers by age, time period and cohort patterns). We also evaluated the number of acute HB in the corresponding inpatient birth-cohorts and special groups.ResultsWe included 2963 participants, mean age = 31.0 ± 14.2, 64.1% women. The birth-cohort 1995–2006, vaccinated after delivery (n = 424, 3-dose HB vaccine coverage > 90%), had significantly lower protective titers (41.3% >10 mIU/mL) compared to the other birth-cohorts: born after 2007 (also vaccinated at birth, 67.0%, n = 106), 1991–1994 (age 9, 74.3%, n = 847), 1986–1990 (age 18, 71.3%, n = 543). In the unvaccinated cohort (n = 1043, mean age = 45.5 ± 12.4) protective titers were found in 44.8%, probably after self-limited HB infection.Concordant results were found using the proportion of patients with detectable or robust titers, and median or geometric mean titers.Four breakthrough acute HB infections were hospitalized of the corresponding vaccinated cohorts (birth years 1988, 1990, 1995, 1996). Data on a few tested infants (n = 47, not included in the main study) demonstrated good protection, 88.9%.ConclusionsOur study demonstrated the long-term evidence of protection of HBV vaccine at two decades following the primary immunization and a booster seems unsupported. Further studies should be done to assess the need of a booster dose within the general population and special groups.     

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.     

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in ≥56-year-olds: A Phase III randomized study

BackgroundInvasive meningococcal disease has a high mortality rate in individuals aged ≥56 years, but no vaccine is currently licensed in the USA for this age group. This study assessed the safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) compared with a meningococcal quadrivalent polysaccharide vaccine (MPSV4) in this age group.MethodsThis was a Phase III, modified double-blind, randomized, non-inferiority study (NCT02842866) across 35 clinical sites in the USA and Puerto Rico in individuals aged ≥56 years. A single dose of the MenACYW-TT (n = 451) or MPSV4 vaccine (n = 455) was administered on Day 0. A serum bactericidal assay with human (hSBA) and baby rabbit (rSBA) complement was used to measure antibodies against serogroups A, C, W, and Y test strains at baseline and Day 30. Safety data were collected up to six months post-vaccination.ResultsThe seroresponse to MenACYW-TT was non-inferior to MPSV4 for each of the serogroups (A: 58.2% vs. 42.5%; C: 77.1% vs. 49.7%; W: 62.6% vs. 44.8%, Y: 74.4% vs. 43.4%, respectively). At Day 30, participants achieving hSBA titers ≥1:8 were higher for all serogroups after MenACYW-TT vs. MPSV4 (77.4–91.7 vs. 63.1–84.2%, respectively). No safety concerns were identified for either vaccine.ConclusionMenACYW-TT was well-tolerated and immunogenic in ≥56-year-olds, offering the potential to replace MPSV4 in this age group.     

Reduced risk of serious pneumococcal infections up to 10 years after a dose of pneumococcal conjugate vaccine in established arthritis

BackgroundTo examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients.MethodsIn total, 595 adult arthritis patients (rheumatoid arthritis; RA = 342, 80 % women and spondylarthropathy; SpA = 253, 45 % women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14 years, respectively. For each patient, 4 matched reference subjects were identified.At vaccination, 420 patients received bDMARDs (anti-TNF = 330, tocilizumab = 15, abatacept = 18, anakinra = 1, rituximab = 56). Methotrexate was given as monotherapy (n = 86) or in combination with bDMARD (n = 220). 89 SpA patients received NSAIDs without DMARD.The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections.ResultsAmong vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections.ConclusionOne dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10 years in patients with arthritis receiving immunomodulating treatment.     

Safety,tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2)

BackgroundThis phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in healthy infants. V114 contains all 13 serotypes in PCV13 and additional serotypes 22F and 33F.MethodsHealthy infants were randomized to two primary doses and one toddler dose (2+1 regimen) of V114 or PCV13 at 3, 5, and 12 months of age; diphtheria, tetanus, pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib), hepatitis B (HepB) vaccine was administered concomitantly. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series, immediately prior to toddler dose, and 30 days post-toddler dose. Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for serotypes 22F and 33F.Results1191 healthy infants were randomized to V114 (n = 595) or PCV13 (n = 596). Proportions of participants with solicited AEs and serious AEs were comparable between groups. V114 met non-inferiority criteria for 13 shared serotypes, based on difference in proportions with serotype-specific IgG ≥0.35 μg/mL (lower bound of two-sided 95% confidence interval [CI] >−10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5) at 30 days post-toddler dose. V114 met superiority criteria for serotypes 22F and 33F, based on response rates (lower bound of two-sided 95% CI >10.0) and IgG GMC ratios (lower bound of two-sided 95% CI >2.0) at 30 days post-toddler dose.Antibody responses to DTaP-IPV-Hib-HepB met non-inferiority criteria, based on antigen-specific response rates.ConclusionA two-dose primary series plus toddler dose of V114 was well-tolerated in healthy infants. Compared with PCV13, V114 provided non-inferior immune responses to 13 shared serotypes and superior immune responses to additional serotypes 22F and 33F.     

Safety and immunogenicity of a quadrivalent seasonal influenza vaccine adjuvanted with hydroxypropyl-β-cyclodextrin: A phase 1 clinical trial

ObjectivesHydroxypropyl-β-cyclodextrin (HP-β-CyD), an oligosaccharide used as an excipient in pharmaceutical preparation, was recently reported to function as a vaccine adjuvant to co-administered antigens. In this study, we investigated the safety and immunogenicity of a seasonal influenza vaccine adjuvanted with HP-β-CyD (FluCyD-vac) in healthy adults compared with those of a standard seasonal influenza vaccine (Flu-vac).MethodsWe conducted a single-blinded randomized phase 1 clinical trial study, and used two quadrivalent split seasonal influenza vaccines: FluCyD-vac containing 9 μg of HA/strain and 20% w/v of HP-β-CyD, and Flu-vac containing 15 μg of hemagglutinin (HA)/strain only. All participants were randomly assigned to receive a single dose of Flu/CyD-vac or Flu-vac at a ratio of 2:1. We assessed solicited and unsolicited adverse events (AEs) and immune responses using hemagglutination inhibition (HI) titers. In addition, we assessed T-cell function in peripheral blood mononuclear cells (PBMCs), after stimulation with HA vaccine strains, using flow cytometry.ResultsAmong 36 healthy volunteers enrolled in the study (FluCyD-vac, n = 24; Flu-vac, n = 12), FluCyD-vac was well tolerated. Most of the solicited AEs were mild local skin reactions at the injection site. No serious AEs were reported in either group. HI titers 21 days after vaccination with FluCyD-vac were comparable with those of Flu-vac and sufficient to meet international criteria, despite reduced HA antigen doses. When PBMCs were stimulated with the four HA antigens in the vaccine, tumor necrosis factor (TNF)-α-producing CD4⁺ T cells were enhanced in the FluCyD-vac group.ConclusionFluCyD-vac was well-tolerated and immunogenic, despite containing 40% less HA antigens than Flu-vac. This study showed that HP-β-CyD is a potentially safe, novel adjuvant for human influenza vaccine.Clinical trial registry: UMIN000028530.