Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine–naïve adults 60–64 years of age

Background

Unlike free pneumococcal polysaccharide vaccines (PPSVs), pneumococcal conjugate vaccines (PCVs) induce a T–cell–dependent immune response. The study assessed potential influence of initial 13-valent PCV (PCV13) or 23-valent PPSV (PPSV23) on subsequent vaccine administrations.

Methods

We conducted a randomized, modified double-blind study in 720 pneumococcal vaccine–naïve adults 60–64 years of age. Subjects received either PCV13 at year 0 and PCV13 at year 1; PCV13 at year 0 and PPSV23 at year 1; or PPSV23 at year 0 and PCV13 at year 1. Antipneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after each vaccination.

Results

OPA titers following PPSV23 given 1 year after PCV13 (PCV13/PPSV23) (a) were noninferior for the 12 common serotypes and significantly higher for 6 of 12 common serotypes than those following only an initial PPSV23; and (b) were significantly higher for 11 of 12 common serotypes compared with PPSV23 followed by PCV13 (PPSV23/PCV13). In addition, PPSV23 followed 1 year later by PCV13 (PPSV23/PCV13) elicited significantly lower OPA titers than after only an initial dose of PCV13 for all 13 serotypes. Responses after a second vaccination with either PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for 9 of 13 and 8 of 12 common serotypes compared with the initial PCV13 dose.

Conclusion

In pneumococcal vaccine–naïve adults 60–64 years of age, an initial PCV13 augmented the antipneumococcal response to subsequent administration of PPSV23 for many of the serotypes in common to both vaccines. In contrast, an initial PPSV23 resulted in a diminished response to subsequent administration of PCV13 for all serotypes. With a relatively short 1-year interval between doses, responses after a second vaccination with PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for a majority of serotypes compared with the initial PCV13 dose, probably reflecting the need for a longer interval between vaccine administrations.ClinicalTrials.gov Identifier: NCT00574548.     

Who is at risk of 13-valent conjugated pneumococcal vaccine failure?

BackgroundDespite high vaccine coverage rates in children and efficacy of pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) episodes due to serotypes included in the vaccine following completion of the recommended course of immunisation (i.e. vaccine failure) have been reported.MethodsWe used data gathered from a population-based enhanced passive surveillance for IPD in children under 18 years of age in Massachusetts and an ensemble model composed of three machine-learning algorithms to predict probability of 13-valent pneumococcal conjugated vaccine (PCV13) failure and to evaluate potential associated features including age, underlying comorbidity, clinical presentation, and vaccine schedule. Vaccine failure was defined as diagnosis of IPD due to vaccine serotype (VST), in a child who received age recommended doses recommended by Advisory Committee of Immunization Practices.ResultsDuring the 7-year study period, between April 01, 2010 and March 31, 2017, we identified 296 IPD cases. There were 107 (36%) IPD cases caused by VST, mostly serotype 19A (49, 17%), 7F (21, 7%), and 3 (18, 6%). Thirty-seven (34%) were in children who were completely vaccinated representing 13% of all IPD cases. Vaccine failure was more likely among children older than 60 months (predicted probability 0.40, observed prevalence 0.37, model prediction accuracy 79%), children presenting with pneumonia (predicted probability 0.27, observed prevalence 0.31, model accuracy 77%), and children with underlying comorbidity (predicted probability 0.24, observed prevalence 0.23, model accuracy 96%). Vaccine failure probability for those >60 months of age and had an underlying risk factor was 45% (observed prevalence 0.33, model accuracy 82%). The likelihood of vaccine failure was lowest among children who had completed 3 primary doses plus one booster dose PCV13 (predicted probability 0.14, observed prevalence 0.14, model prediction accuracy 100%).ConclusionPCV13 vaccine failure is more frequent among older children with underlying comorbidity, and among those who present with pneumococcal pneumonia. Our study provides a preliminary framework to predict the patterns of vaccine failures and may contribute to decision-making processes to optimize PCV immunization schedules.     

Characterization of pneumococcal meningitis before and after introduction of 13-valent pneumococcal conjugate vaccine in Niger, 2010–2018

Pneumococcal meningitis in the African meningitis belt is primarily caused by Streptococcus pneumoniae serotype 1, a serotype contained in the 13-valent pneumococcal conjugate vaccine (PCV13). In 2014, Niger introduced PCV13 with doses given at 6, 10, and 14 weeks of age. We leveraged existing meningitis surveillance data to describe pneumococcal meningitis trends in Niger.As a national reference laboratory for meningitis, Centre de Recherche Médicale et Sanitaire (CERMES) receives cerebrospinal fluid specimens from suspected bacterial meningitis cases and performs confirmatory testing for an etiology by culture or polymerase chain reaction (PCR). Specimens with S. pneumoniae detection during 2010–2018 were sent to the Centers for Disease Control and Prevention for serotyping by sequential triplex real-time PCR. Specimens that were non-typeable by real-time PCR underwent serotyping by conventional multiplex PCR. We tested differences in the distribution of pneumococcal serotypes before (2010–2012) and after (2016–2018) PCV13 introduction.During January 2010 to December 2018, CERMES received 16,155 specimens; 5,651 (35%) had bacterial etiology confirmed. S. pneumoniae accounted for 13.2% (744/5,651); 53.1% (395/744) were serotyped. During 2010–12, PCV13-associated serotypes (VT) constituted three-fourths of serotyped pneumococcus-positive specimens; this proportion declined in all age groups in 2016–18, most substantially in children aged < 5 years (74.0% to 28.1%; P < 0.05). Among persons aged ≥ 5 years, VT constituted > 50% of pneumococcal meningitis after PCV13 introduction; serotype 1 remained the most common VT among persons aged ≥ 5 years, but not among those < 5 years.VT as a group caused a smaller proportion of reported pneumococcal meningitis cases after PCV13 introduction in Niger. Serotype 1, however, remains the major cause of pneumococcal meningitis in older children and adults. Different vaccination strategies, such as changing the infant vaccination schedule or extending vaccine coverage to older children and adults, are needed, in addition to stronger surveillance.     

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naïve adults ≥50 years of age

BackgroundPneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) was evaluated in adults ≥50 years old (NCT01513551).Methods691 adults received one dose of PCV15, PCV13, or 23-valent pneumococcal polysaccharide vaccine (PPV23) and were followed 14 days for safety. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured immediately prior and 1-month postvaccination.ResultsSafety profiles were comparable across vaccination groups. PCV15 induced comparable levels of IgG GMCs and OPA GMTs to PCV13 and PPV23 for shared serotypes. Serotype-specific antibodies were numerically higher among recipients of PCV15 than PCV13 and PPV23 for 7 and 12 shared serotypes, respectively; and lower for 4 and 1 serotype(s), respectively. PCV15 induced higher IgG and OPA antibodies than PCV13 or PPV23 for serotypes unique to PCV15 (22F and 33F not in PCV13; 6A not in PPV23).ConclusionsPCV15 displayed an acceptable safety profile and induced IgG and OPA to all 15 serotypes included in the vaccine, at levels comparable to PCV13 and PPV23 for shared serotypes with these vaccines.Study identification: V114-002.CLINICALTRIALS.GOV identifier: NCT01513551.© 2018 Merck & Co., Inc.     

The effect of 23-valent pneumococcal polysaccharide vaccine on immunological priming induced by 7-valent conjugate vaccine in asplenic subjects with β-thalassemia

The effect of the 23-valent pneumococcal polysaccharide vaccine (PPV) on the 7-valent conjugate (PCV) vaccine-induced priming was evaluated in 35 splenectomised β-thalassemics [median (range) age: 30 (12–41) years] vaccinated with either PCV/PPV or two PCVs 1 month apart, followed by a PPV booster 12 months later. 28/35 had already received 1–3 PPVs in the past. Different schedules induced similar anamnestic responses; however priming for 3/5 serotypes induced by one or two PCVs, was inferior in subjects who had received ≥2 PPVs in the past when compared with 23 aged-matched PPV-naïve β-thalassemics. One PPV following PCV does not affect PCV priming; multiple PPVs induce hyporesponsiveness for some serotypes in splenectomised subjects with β-thalassemia.     

Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in 23-valent pneumococcal polysaccharide vaccine-naïve and previously immunized adult patients with severe chronic kidney disease

Individuals with chronic kidney disease (CKD) are at high risk of pneumococcal infections and recommended to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23). Although the 13-valent pneumococcal conjugate vaccine (PCV13) has been found to have higher immunogenicity compared to PPV23 in adults with some immunocompromising conditions, previous PPV23 immunization may decrease the immunogenicity of PCV13. We assessed immunogenicity and safety of PCV13 in 74 PPV23-naïve and 58 previously PPV23-immunized (>1 year ago) patients with severe (stage 4–5) CKD. Serum IgG, IgM, and IgA specific to seven serotypes, i.e. 3, 6B, 9V, 14, 19A, 19F, 23F were quantified pre- and 4 weeks and one year post-immunization.Baseline concentrations for most serotype-specific IgG and IgM, and serotype 3-specific IgA were higher in previously PPV23-immunized compared to PPV23-naïve patients. Immunization with PCV13 significantly increased almost all serotype-specific IgG, all IgA and some IgM; an increase in some serotype-specific IgG and IgM lasted for one year. Fold increases in antibody concentrations and the proportion of individuals with >2-fold increase post-immunization were generally larger in PPV23-naïve than previously immunized patients for most serotype-specific IgG and some IgA. The data show that in patients with CKD who received previous PPV23 immunization over one year ago, the antibody response to PCV13 was inferior compared to pneumococcal vaccine naïve study participants. In both groups, the lowest response to PCV13 was found for serotype 3. Patients of Indigenous ethnic background demonstrated a superior immune response to PCV13 compared to the non-Indigenous counterpart that could partially be related to Indigenous study participants' younger age. Although we found that previous PPV23 immunization could contribute to the more frequent occurrence of systemic adverse events post PCV13 immunization, those did not exceed the mild to moderate range.     

Public health and economic impact of 13-valent pneumococcal conjugate vaccine in US adults aged ≥50 years

Background

A 13-valent pneumococcal conjugate vaccine (PCV13) was recently developed for use in older adults, and may be effective not only against invasive pneumococcal disease (IPD) but also nonbacteremic pneumococcal pneumonia. The potential public health and economic impact of PCV13 in this population is unknown.

Methods

A microsimulation model depicting risk and costs of IPD and all-cause nonbacteremic pneumonia (NBP) in US adults aged ≥50 years (n = 96.1 million), as well as expected impact of vaccination, was developed. Effectiveness of PPSV23 was based on published literature, and for all-cause NBP, was zero; effectiveness of PCV13 was based on PCV7 data in children, and for all-cause NBP, was varied across a reasonable range. Lifetime outcomes and costs were projected assuming: (1) use of PCV13 in all subjects at model entry, with and without periodic revaccination; and (2) use of PPSV23 per current ACIP recommendations.

Results

Use of PCV13 in all subjects at model entry without revaccination – in lieu of PPSV23 use per recommendations – reduced cases of IPD by 15,000 (95% CI 9000–21,000); cases of NBP by 1.2 million (0.9–1.5); total healthcare costs by $3.5 billion (1.9–5.2); and total societal costs by $7.4 billion (5.3–9.8). Use of PCV13 with revaccination every 5–10 years resulted in fewest cases of disease and lowest total costs. Findings were largely unchanged in sensitivity analyses.

Conclusions

Assuming that the effectiveness of PCV13 in adults is comparable to that observed for PCV7 in children and under reasonable assumptions regarding the underlying risks and costs of IPD and NBP, model projections suggest that routine use of PCV13 – in lieu of PPSV23 – would result in a greater reduction in the overall burden of pneumococcal disease in older US adults.     

Can the response to 23-valent pneumococcal vaccine in splenectomised patients be predicted?

The 23-valent pneumococcal vaccine has unequal effectiveness in splenectomised patients. We performed a longitudinal study (2005-2008) whose main objective was to characterize the profile of non-responders among splenectomised patients treated at our institution and identify potential predictive indicators of the response to the vaccine. The immune response was evaluated in 96 subjects. The proportion of responders was 70% (95% CI: 60-78%). Immunosuppression (OR=3.19, 95% CI 1.04-9.73) and the reason for splenectomy (hematologic neoplasia versus non-malignant hematologic diseases, OR=7.37, 95% CI 1.71-31.7) were independent predictors of non-response to vaccination. However, the positive predictive value of the model and the likelihood ratio for a positive result were low (PPV=76.6%, 95% CI 66.2-84.4%, LR(+)=1.41, 95% CI 1.08-1.86). We recommend determining the response to pneumococcal vaccine in these patients when possible.     

Effectiveness of 23-valent pneumococcal polysaccharide vaccine and seasonal influenza vaccine for pneumonia among the elderly – Selection of controls in a case-control study

We conducted a case-control study to elucidate associations between pneumonia in elderly individuals and 23-valent pneumococcal polysaccharide vaccine (PPSV23) and seasonal influenza vaccine (influenza vaccine). Here, we examined selection of controls in our study using an analytic epidemiology approach. The study period was from October 1, 2009 through September 30, 2014. Cases comprised ≥65-year-old patients newly diagnosed with pneumonia. For every case with pneumonia, two patients with other diseases (one respiratory medicine, one non-respiratory medicine) who were sex-, age-, visit date- and visit hospital-matched were selected as controls. Odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for pneumonia were calculated using conditional logistic regression model. Similar analyses were also conducted based on the clinical department of controls. Analysis was conducted in 234 cases and 438 controls. Effectiveness of pneumococcal vaccination or influenza vaccination against pneumonia was not detected. Proportions of either vaccination in controls were greater among respiratory medicine (pneumococcal vaccine, 38%; influenza vaccine, 55%) than among non-respiratory medicine (23%; 48%). Analysis using controls restricted to respiratory medicine showed marginally significant effectiveness of pneumococcal vaccination (OR, 0.59; 95%CI, 0.34–1.03; P = 0.064) and influenza vaccination (0.64; 0.40–1.04; 0.072). However, this effectiveness might have been overestimated by selection bias of controls, as pneumonia cases are not necessarily respiratory medicine patients. In the analysis using controls restricted to non-respiratory medicine, OR of pneumococcal vaccination for pneumonia was close to 1, presumably because the proportion of pneumococcal vaccination was higher in cases than in controls. Because pneumococcal vaccine was not routinely administered during the study period, differences in recommendations of vaccination by physician in different clinical departments might have greatly affected vaccination proportions. When we select controls, we should consider the background factors (underlying diseases, clinical department, etc.) which affect physicians’ recommendation of vaccination.     

Re-emergence of pneumococcal colonization by vaccine serotype 19F in persons aged ≥5 years after 13-valent pneumococcal conjugate vaccine introduction—Alaska, 2008–2013

BackgroundThe pneumococcal conjugate vaccine (PCV) was introduced in 2001. Widespread PCV use nearly eradicated pneumococcal colonization by vaccine serotypes. Since 2008, however, colonization by PCV-serotype 19F has increased in Alaska residents. We describe the epidemiology of re-emerging serotype 19F colonization.MethodsWe conducted annual cross-sectional colonization surveys from 2008 to 2013. We recruited children aged <5 years at 2 urban clinics and participants of all ages from Region-A (2 villages), Region-B (4 villages), and Region-C (2 villages). We interviewed participants and reviewed their medical records to obtain demographic information and determine PCV status. We obtained nasopharyngeal swab specimens from participants to identify pneumococci and to determine the pneumococcal serotype, antimicrobial resistance, and multilocus sequence type. We used the Cochran-Armitage test to assess for significant trends in colonization across time periods.ResultsAmong participants aged <5 years, pneumococcal serotype 19F colonization remained unchanged from 2008–2009 (0.7%) to 2012–2013 (0.5%; P-value [P] = .54). Serotype 19F colonization increased from 2008–2009 to 2012–2013 among participants aged 5–11 years (0.3% to 3.2%; P < .01), participants 12–17 years (0.0% to 2.0%; P < .01), and participants aged ≥18 years (0.1% to 0.5%; P < .01). During 2012–2013, 85 (93%) of 91 pneumococcal serotype 19F isolates were identified among participants from Region B; the majority of serotype 19F isolates belonged to an antimicrobial nonsusceptibility pattern corresponding to a novel multilocus sequence type 9074.ConclusionsPCV continues to protect against serotype 19F colonization in vaccinated children aged <5 years. The direct PCV impact on serotype 19F colonization in persons aged 5–11 years and indirect impact in persons aged ≥12 years is waning, possibly because of a newly introduced genotype in Region-B.     

Immunogenicity and safety of CRM₁₉₇ conjugated 9-valent pneumococcal and meningococcal C combination vaccine in healthy infants

Streptococcus pneumoniae and Neisseria meningitidis cause invasive disease in children aged <2 years. While individual conjugate vaccines are available to protect this age group against these pathogens, availability of a vaccine combining these antigens into a single injection is desirable. This study randomized 467 healthy infants to receive 4 doses of combination 9-valent pneumococcal and meningococcal serogroup C conjugate vaccine (9vPnC-MnCC) or 9-valent pneumococcal conjugate vaccine (9vPnC). Percentages of subjects achieving immunoglobulin G (IgG) antibody concentrations ≥0.35μg/mL and geometric mean IgG concentrations for each pneumococcal serotype in the 9vPnC-MnCC group were noninferior compared to the 9vPnC group. Both vaccines were well-tolerated.     

Failure to vaccinate or failure of vaccine? Effectiveness of the 23-valent pneumococcal polysaccharide vaccine program in Indigenous adults in the Northern Territory of Australia

Over the last decade, there has been no discernible reduction in Invasive Pneumococcal Disease (IPD) amongst Indigenous adults in the Northern Territory (NT) of Australia, despite increasing vaccination coverage. We examined the utility of two common methods, the screening method and the indirect method, to determine the 23-valent pneumococcal polysaccharide vaccine effectiveness (VE) in prevention of IPD amongst Indigenous adults in this setting. VE was calculated for the period 2001–2005 across two distinct geographical areas where the disease burden was known to differ. VE against vaccine-type IPD was 3.4% (95% CI −43, 35) for the NT. However, population vaccination coverage varied widely according to geographical region and where this was within the range appropriate for the use of the screening method, VE was within the expected range (67.2%, 95% CI 47, 80). VE according to the indirect cohort appeared unreliable in this setting due to the analysis being based on a very limited number of non-vaccine-type IPD cases. Surveillance based estimates of VE such as these need to be considered with caution, but the results suggest failure to vaccinate is the most likely reason vaccine-type IPD has not reduced in this setting.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine and an MF59-adjuvanted influenza vaccine after concomitant vaccination in ⩾60-year-old adults

BackgroundConcomitant administration of influenza and pneumococcal vaccines could be an efficient strategy to increase vaccine uptake among older adults. Nevertheless, immune interference and safety issues have been a concern when more than one vaccines are administered at the same time.MethodsSubjects aged ⩾60 years were randomized in a 1:1:1 ratio to receive MF59-adjuvanted trivalent inactivated influenza vaccine (MF59-aTIV) + 13-valent pneumococcal conjugate vaccine (PCV13) (Group 1), PCV13 alone (Group 2), or MF59-aTIV alone (Group 3). Hemagglutination inhibition (HI) and opsonophagocytic activity (OPA) assays were used to compare immunogenicity after single or concomitant vaccination.ResultsA total of 1149 subjects (Group 1, N = 373; Group 2, N = 394; Group 3, N = 382) were available for the assessment of immunogenicity and safety. All groups met immunogenicity criteria for the influenza vaccine in older adults with similar seroprotection rates, seroconversion rates, and geometric mean titer (GMT) fold-increases, irrespective of concomitant vaccination. For each pneumococcal serotype, OPA titers increased markedly after the PCV13 vaccination, irrespective of the concomitant influenza vaccination. After concomitant administration, the non-inferiority criteria of GMT ratios were met for all three influenza subtypes and 13 pneumococcal serotypes. No vaccine-related serious adverse events occurred.ConclusionsConcomitant MF59-aTIV and PCV13 administration showed no interference with antibody response and showed good safety profiles.(Clinical Trial Number – NCT02215863).     

Clinical effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia in middle-aged and older adults: A matched case–control study

The 23-valent polysaccharide pneumococcal vaccine is currently recommended in elderly and high-risk adults. Its efficacy against invasive pneumococcal disease has been demonstrated, but its effectiveness in preventing pneumonia remains uncertain. This study assessed the clinical effectiveness of vaccination against pneumonia among middle-aged and older adults. We conducted a population-based case–control study including 304 case patients over 50 years old with radiographically confirmed pneumococcal pneumonia (94 bacteremic and 210 nonbacteremic cases) and 608 outpatient control subjects (matched by primary care centre, age, sex and risk stratum). Adjusted odds ratios (ORs) for vaccination were calculated using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness against all pneumococcal pneumonia was 48% (OR: 0.52; 95% confidence interval [CI]: 0.37–0.73). Vaccination was effective against bacteremic cases (OR: 0.34; 95% CI: 0.27–0.66) as well as nonbacteremic cases (OR: 0.58; 95% CI: 0.39–0.86). Vaccine effectiveness was highest against bacteremic infections caused by vaccine types (OR: 0.24; 95% CI: 0.09–0.66). These findings confirm the effectiveness of the vaccine against invasive disease, but they also support the benefit of vaccination in preventing nonbacteremic pneumococcal pneumonia.     

Dynamic changes in clinical characteristics and serotype distribution of invasive pneumococcal disease among adults in Japan after introduction of the pediatric 13-valent pneumococcal conjugate vaccine in 2013–2019

Nationwide population-based surveillance for invasive pneumococcal disease (IPD) is being conducted in few Asian countries. We aimed to evaluate the clinical characteristics and serotype distribution among Japanese adult patients with IPD after introduction of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) in 2013. IPD surveillance was conducted among adults between 2013 and 2019, and 1,995 patients were analyzed by time period (early, 2013–2015; middle, 2016–2017; late, 2018–2019). We found that the period of 2018–2019 was independently associated with a lower risk of fatal outcome, compared with the period of 2013–2015. The proportion of those with serotype PCV13-nonPCV7 decreased significantly in patients aged 15–64 years and in those aged ≥ 65 years within 3 years after the introduction of pediatric PCV13. By contrast, the proportion of those with nonvaccine serotype increased significantly in those aged ≥ 65 years, but not in those aged 15–64 years. No significant change was found in the proportion of 23-valent polysaccharide pneumococcal vaccine (PPSV23)-nonPCV13 in both of adults aged 15–64 years and ≥ 65 years. The proportions of PCV15-, PCV20- and PCV24-covered serotypes were 38%, 56% and 58% in adult patients with IPD aged ≥ 65 years during the late period. Our data on the serotype distribution support an indirect effect from pediatric PCV13 use among adults, and afford a basis for estimates of protection against IPD by vaccination with newly developed PCVs in older adults in Japan.     

Immunogenicity and safety of the adjuvanted recombinant zoster vaccine co-administered with the 23-valent pneumococcal polysaccharide vaccine in adults ≥50 years of age: A randomized trial

BackgroundThis study evaluated immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) when the first dose was co-administered with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults aged ≥50 years.MethodsIn this open label, multi-center study (NCT02045836), participants were randomized 1:1 to receive either the first dose of RZV and PPSV23, co-administered at Day 0 and the second dose of RZV at Month 2 (Co-Ad group), or PPSV23 at Day 0, the first dose of RZV at Month 2 and second dose of RZV at Month 4 (Control group). Co-primary objectives were the RZV vaccine response rate (VRR) in the Co-Ad group and the non-inferiority of the antibody responses to RZV and PPSV23 in the Co-Ad group compared to the Control group. Reactogenicity and safety were also assessed.Results865 participants were vaccinated (Co-Ad: 432, Control: 433). VRRs to RZV were >98% in both groups. Humoral immune responses to co-administration of RZV and PPSV23 were non-inferior to sequential administration. All three co-primary immunogenicity objectives were met. Solicited local symptoms after the first RZV dose were reported by similar percentages of participants in both groups. Solicited general symptoms were more frequently reported when the first dose of RZV and PPSV23 were co-administered. No differences were apparent between groups after the second RZV dose.ConclusionsNo immunologic interference was observed between RZV and PPSV23 when co-administered in adults ≥50 years. No safety concerns were raised.     

Systematic review of economic evaluations of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in individuals 60 years of age or older

ObjectivesTo systematically review the economic evaluations of 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults aged ≥60 years to inform the development of local studies through the discussion of parameters and assumptions that influence the results of the analyses.MethodsWe searched the MEDLINE, Excerpta Medica, Cochrane Library, Latin-American and Caribbean Health Sciences Literature (LILACS), Brazilian Regional Library of Medicine, National Health Service Economic Evaluation, and Centre for Reviews and Dissemination—as well as the Scopus citation index and the Web of Science for full economic evaluations of PPV23 published up to March 2016. Two independent reviewers screened the articles for relevance and extracted the data. Main study characteristics and methods (clinical and epidemiological data, cost and incremental cost-effectiveness ratios (ICERs) were extracted and compared. Costs were updated to 2016 international dollars.ResultsTwenty-seven studies published from 1980 to 2016 were reviewed. Most studies were conducted in Europe and the USA; three studies were conducted in Latin America (Brazil, 2; Colombia, 1). In addition to the scenario comparing the vaccination with the PPV23 to non-vaccination, three studies also compared PPV23 to pneumococcal conjugate 13-valent vaccine (PCV13). All studies used static models. Most used a lifetime (44.4%) or 5–6 year’s time horizon (33.3%). Only three studies considered herd protection from children immunization with PCV13 in the model. Most studies considered PPV23 cost-effective (less than US$50,000 per LYG or QALY) and sometimes cost-saving (results ranging from cost-saving to US$84,636/QALY). The estimates of disease burden, the efficacy/effectiveness of PPV23, and the effects of herd protection from childhood immunization had most influence on the results.ConclusionsWell-designed cost-effectiveness studies of PPV23 that represent the current epidemiological scenario and reduce uncertainty related to efficacy/effectiveness are extremely relevant to informing the decision-making process.     

Nationwide surveillance of paediatric invasive and non-invasive pneumococcal disease in Japan after the introduction of the 13-valent conjugated vaccine, 2015–2017

Streptococcus pneumoniae is still one of the major causes of morbidity and mortality worldwide. In Japan, pneumococcal conjugate vaccine (PCV)7 and PCV13 were licensed in 2010 and 2013, respectively. We conducted a nationwide paediatric invasive pneumococcal disease (IPD) and non-IPD surveillance study in Japan between 2015 and 2017. We collected 498 IPD isolates and 231 non-IPD isolates from a total of 187 medical institutions in Japan. We performed serotyping, antimicrobial susceptibility testing and multi-locus sequencing typing (MLST) for the collected isolates. Among the 498 IPD isolates, the most prevalent serotype was 24F, followed by 12F, 15A and 15B/C. However, 12F increased and 24F significantly decreased during the study period (p < 0.001), resulting in 12F becoming the most prevalent serotype in 2017. Among the IPD isolates, the PCV7 and PCV13 coverage rates were 0.8% and 9.2%, respectively. The most prevalent serotype among the non-IPD isolates was 15A, followed by 35B, 15B/C and 19A. The overall resistance rates to penicillin (PG), cefotaxime (CTX), meropenem (MEM), erythromycin (EM) and levofloxacin (LFX) were 40.5%, 12.2%, 19.4%, 91.8% and 0.5%, respectively. PG, CTX and MEM resistance rates were significantly higher in non-IPD isolates than in IPD isolates (p < 0.001). Serotype 15A-CC63 and serotype 35B-CC558 tended to be multi-drug resistant. In conclusion, the PCV13 coverage rate was significantly lower than that in a previous surveillance study in Japan between 2012 and 2014, and IPD cases attributable to serotype 19A also decreased. We should note the rapid increase in the prevalence of serotype 12F in IPD cases and the spread of the multi-drug resistant serotype 15A-CC63 and 35B-CC558 lineages.     

A randomized, double-blind trial to evaluate immunogenicity and safety of 13-valent pneumococcal conjugate vaccine given concomitantly with trivalent influenza vaccine in adults aged ≥65 years

This randomized, double-blind study evaluated concomitant administration of 13-valent pneumococcal conjugate vaccine (PCV13) and trivalent inactivated influenza vaccine (TIV) in adults aged ≥65 years who were naïve to 23-valent pneumococcal polysaccharide vaccine. Patients (N = 1160) were randomized 1:1 to receive PCV13 + TIV followed by placebo, or Placebo + TIV followed by PCV13 at 0 and 1 months, with blood draws at 0, 1, and 2 months. Slightly lower pneumococcal serotype-specific anticapsular polysaccharide immunoglobulin G geometric mean concentrations were observed with PCV13 + TIV relative to PCV13. Concomitant PCV13 + TIV demonstrates acceptable immunogenicity and safety compared with either agent given alone.