Patient report of herpes zoster pain: Incremental benefits of zoster vaccine live

IntroductionPain following herpes zoster (HZ) can persist for months and negatively impact quality of life. To evaluate the effect of zoster vaccine live (ZVL) on progression of pain following HZ, we conducted a prospective cohort study of HZ cases at Kaiser Permanente Southern California.MethodsZVL vaccinated and unvaccinated members aged ≥60 years with laboratory-confirmed HZ from January 18, 2012 to February 26, 2015 were followed up within 5 days of HZ diagnosis, and at 30, 60, and 90 days after diagnosis. Pain was assessed with the Zoster Brief Pain Inventory (ZBPI) on a 0–10 scale, using cut-points of ≥3, ≥5, and ≥7, with postherpetic neuralgia (PHN) defined as pain ≥3 at 90 days. Log binomial regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) associated with pain, comparing vaccinated versus unvaccinated HZ patients.ResultsWe interviewed 509 vaccinated and 509 unvaccinated HZ patients. ZVL was associated with significantly lower risks of HZ-related pain at all time-points. The risk of PHN in vaccinated and unvaccinated patients, respectively, was 9.2% and 15.4% (aRR = 0.594, 95% CI: 0.413, 0.854); 2.0% and 4.8% of these patients reported pain ≥7 (aRR = 0.332, 95% CI: 0.153, 0.721). Irrespective of vaccination, the risk of PHN was lower in adults aged <70 years versus those ≥70 years and was similar or lower in females versus males.ConclusionWe used laboratory confirmation of HZ cases and patient survey to show that aside from preventing HZ, ZVL reduced HZ-related pain and prevented PHN among vaccine recipients who experienced HZ. Observational studies will be needed to evaluate long-term effectiveness of the new recombinant zoster vaccine and its benefits in protecting patients against PHN.     

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.     

Long-term effectiveness of zoster vaccine live for postherpetic neuralgia prevention

BackgroundPostherpetic neuralgia (PHN) occurs in 5–30% of individuals with herpes zoster (HZ) and is characterized by long-lasting pain. Zoster vaccine live (ZVL) is licensed for people 50 years and older to prevent HZ and PHN. This study evaluated vaccine effectiveness (VE) of ZVL against PHN.MethodsWe conducted an open cohort study within Kaiser Permanente Northern California with continuous accrual of people as they became age-eligible for ZVL. We defined PHN using a PHN diagnosis between 90 and 365 days after an incident episode of HZ. We estimated VE against PHN using Cox regression with a calendar timeline stratified by year of birth and adjusted for sex, race, influenza vaccination, outpatient visit frequency, comorbidities, and immune compromise status.ResultsFrom 2007 to 2016, 1·5 million people entered the study population and 33% received ZVL. During 7·6 million person-years of follow-up, there were 62,205 HZ cases, 4150 (6·7%) of which went on to develop PHN. Overall VE for PHN was 64·8% (95% CI 61·3, 68). VE was 82·8% (95% CI 77·6, 86·7) during the first year after vaccination, 58·3% (95% CI 50.1, 65.2) during the third year, and then waned more gradually to 48·7% (95% CI 30·2, 62·3) during the eighth year. VE in persons vaccinated when aged 80 years or older was similar to VE in younger vaccinees. VE in persons vaccinated when immune compromised was similar to VE in immune competent.ConclusionsOverall, ZVL was 65% effective against PHN. It was effective in all age groups and provided moderate protection through 8 years.     

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.     

Cost-effectiveness of an Adjuvanted Recombinant Zoster Vaccine in older adults in the United States

In the United States, herpes zoster (HZ) and related complications are estimated to result in approximately $1.3 billion in medical care costs and $1.7 billion in indirect costs annually. In this study, we compared the cost-effectiveness of a new Adjuvanted Recombinant Zoster Vaccine (RZV), containing recombinant varicella-zoster virus glycoprotein E and the AS01_B Adjuvant System, versus No Vaccine, as well as versus the live attenuated HZ vaccine (Zoster Vaccine Live (ZVL)) in subjects aged 60+ years of age (YOA) and other age cohorts aged 50+ YOA. A multi-cohort Markov model was developed which follows 1 million individuals over their remaining lifetimes from the year of vaccination with annual cycle lengths. Second dose compliance for RZV was assumed to be 69%. Efficacy and waning parameters were derived from clinical trials for both vaccines. Epidemiological parameters, costs and utility model inputs were derived from US-specific population-based data. Costs and outcomes were discounted at 3% per year. Deterministic and probabilistic sensitivity analysis, along with scenario and threshold analysis were carried out to explore the overall uncertainty in the model. The model estimated that, compared to No Vaccine against HZ, RZV would prevent 103,603 HZ cases, 11,197 postherpetic neuralgia (PHN) cases, and 14,455 other complications, at an incremental cost of $11,863 per quality-adjusted life-year saved from a societal perspective. Compared to ZVL, the model estimated that, RZV would prevent 71,638 additional HZ cases, 6403 PHN cases, and over 10,582 other complications, resulting in net total societal cost savings of over $96 million. The results were robust to a wide range of sensitivity analyses. Vaccination against HZ with RZV is cost-effective compared to No Vaccine and cost-saving compared to ZVL, in the US population aged 60+ YOA.Clinicaltrial.gov. registered#: NA.     

Safety and efficacy of recombinant and live herpes zoster vaccines for prevention in at-risk adults with chronic diseases and immunocompromising conditions

Compared with the general population, older adults with immune senescence and individuals who are immunocompromised (IC) due to disease or immunosuppressive therapy are at increased risk for herpes zoster (HZ) and its associated complications, which can be debilitating and life-threatening. Vaccination can be an effective strategy against HZ and studies have shown that HZ vaccination in IC individuals can elicit immune responses and provide protection from infection. Recently, the first approvals have been granted in the United States and the European Union for the recombinant HZ vaccine (RZV) in adults ≥ 18 years of age at risk of HZ due to immunodeficiency or immunosuppression. Existing systematic reviews have highlighted the risks for HZ in limited immunocompromising conditions and have only examined clinical data for RZV. This review details the risks and burden of HZ in a broad range of clinically relevant IC populations and summarizes key efficacy and safety data for RZV and live HZ vaccine in these individuals. Research has shown IC individuals can benefit from HZ vaccination; however, these insights have yet to be fully incorporated into vaccination guidelines and clinical care. Clinicians should consider HZ vaccination in eligible at-risk populations to protect against HZ and its associated complications and thereby, reduce the burden that HZ poses on the healthcare system. Electronic health records and linked personal health records could be used to identify and contact patients eligible for HZ vaccination and provide clinical decision support-generated alerts for missing or delayed vaccinations. This review will help clinicians identify eligible IC individuals who may benefit from HZ vaccination.A video abstract linked to this article is available on Figshare https://doi.org/10.6084/m9.figshare.21517605.     

Primary care physicians’ experience with zoster vaccine live (ZVL) and awareness and attitudes regarding the new recombinant zoster vaccine (RZV)

BackgroundThe Advisory Committee on Immunization Practices (ACIP) has routinely recommended zoster vaccine live (ZVL) for adults ≥60 since 2008; only 33% of eligible adults received it by 2016. A recombinant zoster vaccine (RZV) was licensed in 2017 and ACIP recommended in January 2018. Our objectives were to assess among primary care physicians (1) practices and attitudes regarding ZVL and (2) awareness of RZV.MethodsWe administered an Internet and mail survey from July to September 2016 to national networks of 953 primary care physicians.ResultsResponse rate was 65% (603/923). Ninety-three % of physicians recommended ZVL to adults ≥60, but fewer recommended it to adults ≥60 with a prior history of zoster (88%), adults > 85 (62%) and adults ≥60 on low-dose methotrexate (42%). Several physicians recommended ZVL in ways that are not recommended by ACIP including to adults 50–59 (50%), adults ≥60 with HIV (33%), and adults ≥60 on high dose prednisone (≥20 mg/day) (27%). Nineteen percent of physicians stocked and administered ZVL and did not refer patients elsewhere for vaccination, 37% did not stock and only referred patients to receive it, and 44% both stocked/administered and referred elsewhere. Twenty-three % (n = 115) of physicians who had ever administered ZVL in the office (n = 490) had stopped, citing primarily financial issues (90%). Only 5% were ‘very aware’ of RZV.ConclusionsPhysicians report not recommending ZVL to certain ACIP-recommended groups, but report recommending it to some groups for which the vaccine should be avoided. Implementation of recommendations for RZV will need to consider financial barriers and the complex patchwork of office-based and pharmacy delivery ZVL has encountered.     

The burden of herpes zoster disease in Norway

BackgroundNo national vaccination program against herpes zoster (HZ) is currently in place in Norway. We aimed to quantify the burden of medically attended HZ to assess the need for a vaccination program.MethodsWe linked data from several health registries to identify medically attended HZ cases during 2008–2014 and HZ-associated deaths during1996–2012 in the entire population of Norway. We calculated HZ incidences for primary and hospital care by age, sex, type of health encounter, vaccination status, and co-morbidities among hospital patients. We also estimated HZ-associated mortality and case-fatality.ResultsThe study included 82,064 HZ patients, of whom none were reported as vaccinated against HZ. The crude annual incidence of HZ was 227.1 cases per 100,000 in primary healthcare and 24.8 cases per 100,000 in hospitals. Incidence rates were higher in adults aged ≥50 years (461 per 100,000 in primary care and 57 per 100,000 in hospitals), and women than in men both in primary healthcare (267 vs 188 per 100,000), and hospitals (28 vs 22 per 100,000). Among hospital patients, 47% had complicated zoster and 25% had comorbidities, according to the Charlson comorbidity index. The duration of hospital stay (median 4 days) increased with the severity of comorbidities. The estimated mortality rate was 0.18 per 100,000; and in-hospital case-fatality rate was 1.04%.ConclusionsMedically attended HZ poses a substantial burden in the Norwegian healthcare sector. The majority of the zoster cases occurred among adults aged ≥50 years – the group eligible for zoster vaccination – and increased use of zoster vaccination may be warranted, especially among persons with co-morbidities.     

Efficacy of the adjuvanted recombinant zoster vaccine (RZV) by sex,geographic region,and geographic ancestry/ethnicity: A post-hoc analysis of the ZOE-50 and ZOE-70 randomized trials

BackgroundHerpes zoster (HZ) risk appears to vary by sex and geographic ancestry/ethnicity.MethodsIn 2 randomized clinical trials, participants received 2 doses of adjuvanted recombinant zoster vaccine (RZV) or placebo intramuscularly, 2 months apart. In this post-hoc analysis, we investigate efficacy of RZV against HZ and postherpetic neuralgia (PHN) by sex, geographic region, and geographic ancestry/ethnicity in ≥50-year-olds (ZOE-50: NCT01165177) and ≥70-year-olds (pooled data from ZOE-50 and ZOE-70: NCT01165229).ResultsVaccine efficacy against HZ or PHN was similar in women and men. Across geographic regions, efficacy against HZ ranged between 95.7 and 97.2% in ≥50-year-olds, and between 87.3% and 95.1% in ≥70-year-olds; efficacy against PHN ranged between 86.8 and 100% in ≥70-year-olds. Across ancestral/ethnic groups, efficacy ranged between 88.1 and 100% against HZ and between 65.9 and 100% against PHN in ≥70-year-olds.ConclusionsWhile the ZOE-50/70 studies were not powered or pre-designed for these post-hoc analyses, RZV appears efficacious against HZ and PHN irrespective of sex, region, or geographic ancestry/ethnicity.     

Immunogenicity and safety of MF59-adjuvanted quadrivalent influenza vaccine versus standard and alternate B strain MF59-adjuvanted trivalent influenza vaccines in older adults

ObjectiveEvaluate whether adjuvanted quadrivalent influenza vaccine (aQIV) elicits a noninferior immune response compared with a licensed adjuvanted trivalent influenza vaccine (aTIV-1; Fluad™) and aTIV-2 containing an alternate B strain, examine whether aQIV had immunological superiority for the B strain absent from aTIV comparators, and evaluate reactogenicity and safety among adults ≥65 years.MethodsIn a multicenter, double-blind, randomized controlled trial, adults ≥65 years were randomized 2:1:1 to vaccination with aQIV (n = 889), aTIV-1 (n = 445), or aTIV-2 (n = 444) during the 2017-2018 influenza season. Immunogenicity was assessed by hemagglutination inhibition (HI) assay conducted on serum samples collected before vaccination and 21 days after vaccination for homologous influenza strains.ResultsaQIV met non-inferiority criteria for geometric mean titer ratios (GMT ratios) and seroconversion rate (SCR) differences against aTIV. The upper bounds of the 2-sided 95% confidence interval (CI) for GMT ratios were <1.5 for all 4 strains (A/H1N1 = 1.27, A/H3N2 = 1.09, B-Yamagata = 1.08, B-Victoria = 1.08). The upper bounds of the 95% CI of the SCR differences were <10% for all 4 strains (A/H1N1 = 7.76%, A/H3N2 = 4.96%, B-Yamagata = 3.27%, B-Victoria = 2.55%). aQIV also met superiority criteria (upper bound of 95% CI for GMT ratios <1 and SCR differences <0) for B strain absent from aTIV comparators (B-Yamagata GMT ratio = 0.70, SCR difference = −8.81%; B-Victoria GMT ratio = 0.78, SCR difference = −8.11%). aQIV and aTIV vaccines were immunogenic and well-tolerated. The immunological benefit of aQIV was also demonstrated in age subgroups 65–74 years, 75–84 years, and ≥85 years and in those with high comorbidity risk scores. Reactogenicity profiles were generally comparable.ConclusionaQIV induces a similar immune response as the licensed aTIV vaccine against homologous influenza strains and has a comparable reactogenicity and safety profile. Superior immunogenicity against the additional B strain was observed, indicating that aQIV could provide a broader protection than aTIV against influenza in older adults (NCT03314662).     

Post-licensure safety study of new-onset immune-mediated diseases,herpes zoster,and anaphylaxis in adult recipients of HepB-CpG vaccine versus HepB-alum vaccine

BackgroundHepB-CpG (Heplisav-B) is a licensed hepatitis B vaccine with a novel adjuvant that requires 2 doses (0, 1 month) compared to HepB-alum (Engerix-B) which requires 3 doses (0, 1, 6 months). Monitoring safety outcomes following receipt of vaccines with novel adjuvants outside trial settings is important. Hence, as part of a post-marketing commitment, we compared the incidence of new-onset immune-mediated diseases, herpes zoster (HZ), and anaphylaxis among recipients of HepB-CpG versus HepB-alum.MethodsThis cohort study included adults not on dialysis who received ≥1 dose of hepatitis B vaccine from 8/7/2018 to 10/31/2019, during which HepB-CpG was routinely administered in 7 of 15 Kaiser Permanente Southern California medical centers while HepB-alum was administered in the other 8 centers. Recipients of HepB-CpG or HepB-alum were followed through electronic health records for 13 months for occurrence of pre-specified new-onset immune-mediated diseases, HZ, and anaphylaxis identified using diagnosis codes. Incidence rates were compared using Poisson regression with inverse probability of treatment weighting when there was ≥80 % power to detect a relative risk (RR) of 5 for anaphylaxis and RR of 3 for other outcomes. Chart review to confirm new-onset diagnosis was conducted for outcomes with statistically significant elevated risk.ResultsThere were 31,183 HepB-CpG and 38,442 HepB-alum recipients (overall 49.0 % female, 48.5 % age ≥50 years, and 49.6 % Hispanic). Among immune-mediated events that occurred frequently enough for formal comparison, rates among HepB-CpG versus Hep-B-alum recipients were similar except for rheumatoid arthritis (RA) (adjusted RR 1.53 [95 % CI: 1.07, 2.18]). After chart confirmation of new-onset RA, the adjusted RR was 0.93 (0.34, 2.49). The adjusted RR for HZ was 1.06 (0.89, 1.27). Anaphylaxis occurred in 0 HepB-CpG and 2 HepB-alum recipients.ConclusionsThis large post-licensure study did not identify evidence of safety concerns for HepB-CpG compared to HepB-alum for immune-mediated diseases, HZ, or anaphylaxis.     

Incidence of herpes zoster among varicella-vaccinated children,by number of vaccine doses and simultaneous administration of measles,mumps, and rubella vaccine

IntroductionChildren may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration.MethodsIn six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003–2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR.ResultsAmong 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups.ConclusionsHZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.     

Effectiveness of the recombinant zoster vaccine among Kaiser Permanente Hawaii enrollees aged 50 and older: A retrospective cohort study

BackgroundThe incidence of herpes zoster (HZ) has been on the rise for decades in the United States. Clinical trials for the recombinant zoster vaccine (RZV) demonstrated vaccine efficacy of over 90% in preventing herpes zoster. However, there is limited information on its effectiveness outside of a clinical trial setting, as well as its effectiveness against herpes zoster ophthalmicus (HZO).MethodsA de-identified electronic health records database from Kaiser Permanente Hawaii (KPH) was used to conduct this retrospective cohort study to assess the effectiveness of the recombinant zoster vaccine against HZ and HZO in immunocompetent, vaccine age-eligible individuals without a prior history of HZ, who were continuously enrolled in KPH for ≥365 days prior to becoming age-eligible for RZV between January 1, 2018, through December 31, 2019.ResultsA total of 78 356 adults were included in this study, with 11 864 (15.1%) adults receiving two valid doses of the recombinant zoster vaccine. The incidence rate of HZ was 325.6 (95% CI: 217.7 to 464.4) cases per 100 000 person-years in vaccinated persons compared to 1063.3 cases per 100 000 person-years (95% CI: 1006.0 to 1122.8) in the unvaccinated group. The incidence rate of HZO was 11.9 (95% CI: 0.7 to 52.3) cases per 100 000 person-years in the vaccinated group compared to 72.1 (95% CI: 58.0 to 88.3) in the unvaccinated group. RZV was 83.5% (95% CI: 74.9% to 89.2%) effective against HZ and 93.3% (95% CI: 48.7% to 99.1%) effective against HZO.ConclusionsRZV has demonstrated high effectiveness against both HZ and HZO outside of a clinical trial setting in the United States. Vaccine coverage is low, emphasizing the need for public health efforts to increase vaccination to reduce morbidity from HZ and HZO.     

Real-world evidence on adherence and completion of the two-dose recombinant zoster vaccine and associated factors in U.S. adults, 2017–2021

IntroductionPoor compliance with adult vaccination recommendations contributes to substantial disease burden. Evidence on adherence, completion, and completion timeliness for the 2-dose recombinant herpes zoster vaccine (RZV) and factors associated with these outcomes is limited and not readily generalizable for the entire U.S.MethodsThis retrospective, observational study examined adherence, completion, and the impact of sociodemographic, clinical and geographical factors among U.S. adults ≥ 50 years receiving RZV (4/20/2017 to 3/31/2021), using a large, geographically representative administrative claims database. Continuous enrollment in a medical benefit plan for six months prior to and following the index date (first observed vaccine dose) was required. Adherence was defined as receipt of the 2nd dose within 2–6 months, per label recommendation. Completion (receipt of all doses) was assessed at 6, 12, 18, and 24 months.ResultsAmong 726,352 adults included, the adherence rate was 71.8%. Among 208,311 adults with 24–month follow-up, the completion rate was 72.3% after 6 months and 86.2% after 24 months. Logistic regression showed low adherence/completion was associated with younger age, Black or Hispanic race/ethnicity, lower income, lower educational attainment, and possessing commercial rather than Medicare healthcare insurance. Recipients identified using pharmacy claims had much higher adherence (74.0%) than those identified using medical claims (48.0%).ConclusionsAdherence and completion rates for RZV are suboptimal, especially for adults aged 50–64, racial/ethnic minorities, individuals with lower socio-economic status and those without Medicare insurance. More research and public health efforts are needed to understand and address potential barriers to RZV uptake, adherence and completion.     

Safety of the adjuvanted recombinant zoster vaccine in adults aged 50 years or older. A phase IIIB,non-randomized,multinational, open-label study in previous ZOE-50 and ZOE-70 placebo recipients

BackgroundEfficacy of the adjuvanted recombinant zoster vaccine (RZV) against herpes zoster (HZ) was demonstrated in pivotal trials ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229). This study was designed to offer RZV to placebo recipients of these parent studies.MethodsVaccine safety and suspected HZ episode occurrence were assessed for 12 months following vaccination.ResultsOf the 14,550 eligible participants, 8687 received RZV and 97.8% completed the 2-dose schedule. During the 30-day post-vaccination period, 5175 (59.6%) participants experienced ≥ 1 unsolicited adverse event (AE), 4422 (50.9%) were vaccination-related. The most common AEs were injection-site reactions, pyrexia, and headache. During the study, 734 (8.4%) participants reported ≥ 1 serious AE (SAE) and 62 (0.7%) reported ≥ 1 potential immune-mediated disease (pIMD); 2 of each were assessed as vaccination-related. Suspected HZ episodes were reported by 30 participants (0.3%).ConclusionsNature and incidence of AEs, SAEs, and pIMDs were as expected and in line with the parent studies.     

Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: A systematic review and pooled analysis

BackgroundSerotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease.MethodsWe performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data.ResultsTwo published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2–75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7–76.9%]). No heterogeneity was observed.ConclusionsCurrently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.     

Randomized trial to evaluate the safety,tolerability, and immunogenicity of a booster (third dose) of BNT162b2 COVID-19 vaccine coadministered with 20-valent pneumococcal conjugate vaccine in adults ≥65 years old

BackgroundOlder adults are at increased risk of adverse outcomes from pneumococcal disease and COVID-19. Vaccination is an established strategy for preventing both illnesses. This study evaluated the safety and immunogenicity of coadministration of the 20-valent pneumococcal conjugate vaccine (PCV20) and a booster (third dose) of BNT162b2 COVID-19 vaccine.MethodsThis phase 3, randomized, double-blind, multicentre study included 570 participants aged ≥65 years randomized 1:1:1 to PCV20 and BNT162b2 coadministered, or PCV20 or BNT162b2 only (administered with saline for blinding). Primary safety endpoints included local reactions, systemic events, adverse events (AEs) and serious AEs (SAEs). Secondary objectives were immunogenicity of PCV20 and BNT162b2 when administered together or separately.ResultsCoadministration of PCV20 and BNT162b2 was well tolerated. Local reactions and systemic events were generally mild-moderate; injection-site pain and fatigue were the most frequent local and systemic events, respectively. AE and SAE rates were low and similar across groups. No AEs led to discontinuation; no SAEs were considered vaccination-related. Robust immune responses were observed, with opsonophagocytic activity geometric mean fold rises (GMFRs; from baseline to 1 month) of 2.5–24.5 and 2.3–30.6 across PCV20 serotypes in Coadministration and PCV20-only groups, respectively. GMFRs for full-length S-binding IgG of 35.5 and 39.0, and for neutralizing titres against SARS-CoV-2-wild type virus of 58.8 and 65.4, were observed in the Coadministration and BNT162b2-only groups, respectively.ConclusionsSafety and immunogenicity of coadministered PCV20 and BNT162b2 were similar to those of PCV20 or BNT162b2 administered alone, suggesting that the 2 vaccines may be coadministered.Trial Registration: ClinicalTrials.gov, NCT04887948.     

Impact of patient and provider nudges on addressing herpes zoster vaccine series completion

ObjectivesTo determine the combined impact of provider-facing and text message-based, patient nudges on herpes zoster vaccine series completion.MethodsFollowing a period during which Kroger Health implemented provider facing nudges, select US patients that initiated herpes zoster vaccination were randomized to receive timed text messages when the second dose was due and available as part of a quality improvement exercise. Main comparisons were between patients intervened by provider nudge only and those intervened by both provider and patient nudges. Data were assessed by GEE-based logistic and linear regression, controlling for available patient- and store-level characteristics, and geospatial analyses.ResultsDuring the baseline period, 100,627 adults received at least one HZ vaccine dose and 83.9% completed the series within 6 months over 88.6 days (SD: 26.53) on average. In the intervention period, 120,339 adults were vaccinated at least once and series completion was 88.3% (both provider nudges and text messaging) and 85.3% (not texted) during this observation window (both p < 0.0001). Time between doses was shorter for those who received text messages compared to both the baseline period and those in the intervention period that were not texted (both p < 0.001). Controlling for multiple characteristics, the odds of completion improved in the intervention period compared to baseline (OR: 1.07; 95% CI: 1.033–1.111), but a noticeably higher completion odds was observed amongst patients who received a text message in the intervention period (OR: 1.35; 95% CI: 1.286–1.414). Adjusting for patient and pharmacy factors, those who were texted received their second herpes zoster vaccine dose 8.6 days sooner (95% CI: ?9.08 - ?8.17, p < 0.0001) compared to those intervened by the provider nudge only.ConclusionThe combined use of clinical and patient-focused nudges is a simple mechanism by which pharmacies and other health care access points can address the multi-dose vaccine needs of diverse patient populations.     

Safety,tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine,followed by sequential PPSV23 vaccination in healthy adults aged ≥50 years: A randomized phase III trial (PNEU-PATH)

BackgroundStreptococcus pneumoniae causes pneumococcal disease, and older adults are at an increased risk. Sequential vaccination of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for broad protection against pneumococcal disease in some countries.MethodsThis phase III trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 12 months later by PPSV23, in healthy adults aged ≥50 years (NCT03480763). A total of 652 participants were randomized 1:1 to receive either V114 or PCV13, followed by PPSV23.ResultsThe most common solicited adverse events (AEs) following PCV vaccination included injection-site pain and fatigue. Higher proportions of participants with these events were observed in the V114 group following PCV; however, these differences were not clinically significant. Following PPSV23 vaccination, the most common solicited AEs were injection-site pain and injection-site swelling; the proportions of participants with these events were comparable between both groups. Incidence of serious AEs was low in both groups following PCV and PPSV23, and none were related to study vaccines. No deaths occurred during the study. Serum opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations were comparable between both groups for all 15 serotypes in V114 following PPSV23. Immune responses elicited by V114 persisted for at least 12 months. Immune responses at 30 days and 12 months post-vaccination with PCV were comparable between both groups for the 13 shared serotypes and higher in the V114 group for the V114-unique serotypes (22F and 33F).ConclusionAdministration of V114 followed by PPSV23 was well tolerated and induced comparable antibody levels to PCV13 followed by PPSV23 in healthy adults aged ≥50 years.