Pneumococcal conjugate vaccine use during humanitarian crises

Streptococcus pneumoniae is a common human commensal that causes a sizeable part of the overall childhood mortality in low income settings. Populations affected by humanitarian crises are at especially high risk, because a multitude of risk factors that are enhanced during crises increase pneumococcal transmission and disease severity. Pneumococcal conjugate vaccines (PCVs) provide effective protection and have been introduced into the majority of routine childhood immunisation programmes globally, though several barriers have hitherto limited their uptake during humanitarian crises. When PCV coverage cannot be sustained during crises or when PCV has not been part of routine programmes, mass vaccination campaigns offer a quick acting and programmatically feasible bridging solution until services can be restored. However, we currently face a paucity of evidence on which to base the structure of such campaigns. We believe that, now that PCV can be procured at a substantially reduced price through the Humanitarian Mechanism, this lack of information is a remaining hurdle to PCV use in humanitarian crises. Considering the difficulties in conducting research in crises, we propose an evidence generation pathway consisting of primary data collection in combination with mathematical modelling followed by quasi-experimental evaluation of a PCV intervention, which can inform on optimal vaccination strategies that consider age targeting, dosing regimens and impact duration.     

Clinical features of adults with seven-valent-conjugated-vaccine-serotype pneumococcal pneumonia

Background

Despite the reduction in adult invasive pneumococcal disease through ‘herd protection’ consequent to the introduction of childhood pneumococcal conjugate vaccination (PCV), a significant proportion of adults continue to develop pneumococcal pneumonia caused by one of the seven serotypes included in the seven-valent conjugated pneumococcal vaccine (PCV7). The clinical features and outcomes of these adults have not been previously reported.

Methods

Adults recruited over a three year period to a large prospective cohort study of community acquired pneumonia (CAP) were investigated for pneumococcal serotypes using a validated multiplex immunoassay (Bio-plex). The baseline characteristics and outcomes of adults with PCV7-serotype CAP in comparison to those with non-PCV7-serotype CAP were established.

Results

Pneumococcal aetiology was identified in 415 of 1166 (35.6%) individuals, and a serotype determined in 287 (69.2%). Following exclusion of three individuals with both a PCV7 and non-PCV7 serotype, 77 of the remaining 284 (27.1%) adults had CAP due to PCV7 serotypes. Adults with PCV7-serotype CAP were older (median years (inter-quartile range) 73.3 (60.8–84.4) versus 65.0 (46.1–78.0); p = 0.001) and were more likely to have a World Health Organisation performance status ≥1 (odds ratio (OR) 2.05, 95% confidence interval (CI) 1.21–3.50).The presence of stroke (adjusted OR 2.84, 95% CI 1.36–5.95) and dementia (adjusted OR 3.55, 95% CI 1.26–9.94) as underlying co-morbid illnesses were independently associated with PCV7-serotype CAP; 30-day mortality was significantly greater in adults with PCV7-serotype CAP (adjusted OR 4.38, 95% CI 1.85–10.34).

Conclusion

A significant proportion of adults continue to develop PCV7-serotype CAP in the era of childhood pneumococcal conjugate vaccination. These adults are more likely to have stroke and dementia as underlying co-morbid illnesses, and have a higher 30-day mortality. A combination of pneumococcal transmission factors, host factors and pneumococcal serotype specific characteristics are likely to explain these findings.     

Pneumococcal conjugate vaccine failure in children: A systematic review of the literature

BackgroundPneumococcal conjugate vaccines (PCVs) are highly effective in preventing pneumococcal invasive disease (IPD) due to serotypes included in the vaccines. The risk of vaccine-type IPD in immunised children (i.e. vaccine failure) has not been systematically assessed in countries with established PCV programmes.MethodsWe undertook a systematic review of the English literature published from January 2000 to April 2016 to evaluate the vaccine schedule, risk factors, serotype distribution, clinical presentation and outcomes of vaccine failure in children vaccinated with the 7-valent (PCV7), 10-valent (PCV10), and 13-valent (PCV13) vaccines. Data sources included MEDLINE, EMBASE, Cochrane library, and references within identified articles.ResultsWe identified 1742 potential studies and included 20 publications involving 7584 participants in children aged ⩽5 year-olds: 5202 received 2 doses followed by a booster in 10 studies, (68.6%), 64 (0.8%) received 3 doses without a booster in 2 studies, and 2318 received a 3 + 1 schedule (30.6%) in 8 studies. A total of 159 vaccine failure cases were identified, representing 2.1% [95% CI: 1.8–2.4%] of the reported IPD cases. Most studies did not report clinical characteristics or outcomes. Among eight studies reporting comorbidities, 33/77 patients (42.9%) had an underlying condition. The main serotypes associated with vaccine failure were 19F (51/128 cases with known serotype; 39.8%), 6B (33/128; 25.8%), and 4 (10/128; 7.8%). Only five studies reported patient outcomes, with a crude case fatality rate of 2.4% (2/85; 95%CI: 0.3–8.5%).ConclusionPneumococcal conjugate vaccines have been implemented in national immunisation programmes for more than a decade, yet there are only a few studies reporting vaccine failure. PCV failure is rare, irrespective of vaccine or schedule. Co-morbidity prevalence was high amongst vaccine failure cases but case fatality rate was relatively low. There is a need for more systematic reporting vaccine failure cases in countries with established pneumococcal vaccination programmes.     

Public health and economic impact of the 13-valent pneumococcal conjugate vaccine (PCV13) in the United States

The 7-valent pneumococcal conjugate vaccine (PCV7) has dramatically decreased pneumococcal disease incidence, and the 13-valent vaccine (PCV13) protects against 6 additional Streptococcus pneumoniae serotypes. A decision-analytic model was constructed to evaluate the impact of infant vaccination with PCV13 versus PCV7 on pneumococcal disease incidence and mortality as well as the incremental benefit of a serotype catch-up program. PCV13 effectiveness was extrapolated from observed PCV7 data, using assumptions regarding serotype prevalence and PCV13 protection against additional serotypes. The model predicts that PCV13 is more effective and cost saving compared with PCV7, preventing 106,000 invasive pneumococcal disease (IPD) cases and 2.9 million pneumonia cases, and saving $11.6 billion over a 10-year period. The serotype catch-up program would prevent an additional 12,600 IPD cases and 404,000 pneumonia cases, and save an additional $737 million compared with no catch-up program.     

Acceptance of pneumococcal vaccination in older adults: A general population-based survey

BackgroundPneumococcal infection is a leading cause of disability and death globally. The Hong Kong Government has launched two programmes for pneumococcal vaccination - The Vaccination Subsidy Scheme (VSS) and the Government Vaccination Programme (GVP). This study aimed to examine the enabling factors, obstacles and perception of pneumococcal vaccination, and their association with its uptake in a general Chinese population.MethodsWe performed a population-based, telephone survey in the general public aged 65 or above via simple random sampling. A validated survey based on the Health Belief Model (HBM) was used. Their socio-demographic information; history of previous participation in the GVP or VSS; and self-perceived health status were captured. Binary logistic regression models were constructed to examine the factors independently associated with vaccination.ResultsA total of 1,000 respondents were enrolled in the study, with 402 (40.2%) respondents having intention to join the GVP/VSS in 12 months. Respondents with long-term medical consultant and medication (adjusted odds ratios [aOR] = 1.541, 95% confidence interval (CI): 1.008–2.356, p = 0.046); high levels of perceived susceptibility of infections (aOR = 3.624, 95 %CI: 2.318–5.665, p < 0.001); high levels of perceived benefits of vaccine (aOR = 1.699, 95 %CI: 1.153–2.504, p < 0.001); recommendations from government (aOR = 8.025, 95 %CI: 4.771–13.497, p < 0.001) or physicians (aOR = 7.399, 95 %CI: 3.472–15.764, p = 0.008); and high levels of self-efficacy (aOR = 3.045, 95 %CI: 1.458–6.362, p = 0.003) were more likely to have intention to participate in the vaccination programme.ConclusionsThe acceptance rate of pneumococcal vaccination programme remained suboptimal in the population. The government and physicians should be involved in the promotion of pneumococcal vaccination and GVP/VSS by increasing perceived benefits and self-efficacy, and reducing barriers towards vaccination among the target population. More studies are required to confirm our findings in other settings.     

Pneumococcal polysaccharide 23-valent vaccine: long-term persistence of circulating antibody and immunogenicity and safety after revaccination in adults

Since publication of a 1997 review of the immunogenicity and safety data for pneumococcal polysaccharide vaccines (PPSVs), dozens of additional studies have been published, involving larger cohorts, longer observation periods, and more specific assays. Additionally, a 13-valent pneumococcal conjugate vaccine (PCV) has been licensed for adults. This paper reviews adult studies assessing antibody persistence for ≥ 3 years after pneumococcal vaccination, and adult studies of immunogenicity and safety after revaccination. This review emphasizes the currently registered PPSV23 formulations containing 25-μg polysaccharide per serotype, for which far more long-term data are available. Broadly, IgG and functional antibody levels after PPSV23 in adults persist above concentrations in unvaccinated adults for at least 5-10 years in most studies. The few exceptions involve populations of non-ambulatory adults or those with confounding host-factor issues. Revaccination with PPSV23 5-10 years after a previous dose consistently and substantially increases both IgG and functional antibody levels. There is an inverse association between circulating antibody level just before primary or revaccination and subsequent antibody increase. Although injection-site reactions (e.g., pain, swelling, redness) were reported more commonly after PPSV23 revaccination than after primary vaccination in most studies, these reactions typically resolved within 5 days. We interpret the contemporary literature as supporting pneumococcal revaccination as a means to sustain anti-pneumococcal antibodies at levels greater than among unvaccinated adults. PPSV23 is a broad-spectrum public-health tool to help prevent serious pneumococcal diseases across the adult lifespan.     

13-Valent vaccine serotype pneumococcal community acquired pneumonia in adults in high clinical risk groups

There is debate regarding the value of vaccinating adults with the 13-valent pneumococcal conjugate vaccine (PCV-13). This analysis was conducted to investigate the risk of PCV-13 serotype community acquired pneumonia (CAP) in hospitalised adults with co-morbid disease and risk factors for pneumococcal disease in the UK.Consecutive adults hospitalised (2008–2013) with a primary diagnosis of CAP, were recruited. Pneumococcal aetiology disease was identified by use of pneumococcal urinary antigen detection and serotype identification using a validated multiplex immunoassay or serum latex agglutination. Adults with PCV-13 serotype CAP were compared to those with non-PCV-13 serotype CAP.Of 2224 patients, PCV-13 serotype CAP was identified in 337 (15.2%) and non-PCV-13 serotype CAP in 250 (11.2%) individuals. Adults aged ≥65 years with one or more clinical risk factors had a significantly lower risk of PCV-13 serotype CAP compared to those aged 16–64 years without clinical risk factors (aOR 0.61, 95%CI 0.41–0.92, p = .018). In a stacked-risk analysis, the presence of incremental clinical risk factors was associated with lower odds of PCV-13 disease (p for trend = .029) Adults with underlying chronic respiratory disease (aOR) 0.56, 95% CI 0.36–0.85, p = .007) and chronic kidney disease (aOR 0.48, 95% CI 0.25–0.92, p = .028) had significantly lower adjusted odds of PCV-13 compared to non-PCV-13 serotype CAP.This analysis suggests that in the UK, the burden of PCV13 disease is greater in adults outside the traditional ‘at-risk’ groups compared to adults in ‘at-risk’ groups.     

Pneumococcal vaccination patterns among persons aged 65 years or older in the United States: A retrospective database analysis

ObjectiveThis study investigated the patterns of pneumococcal disease vaccination, the time between two different pneumococcal vaccine doses and factors associated with series completion.MethodsA retrospective claims database analysis was conducted using the Clinformatics DataMart™ database. Adults who turned 65 years between January 1st, 2013 to June 30th, 2017 and were continuously enrolled (≥15 months) in the Medicare Advantage plans to June 30th, 2017 were included in this study. Pneumococcal vaccination patterns included: PCV13-PPV23, PPV23-PCV13, or receiving PPV23 or PCV13 only. Pneumococcal vaccination series completion was defined as receiving PCV13-PPV23 or PPV23-PCV13 from 65 years old to June 30th, 2017 while non-completion was defined as receiving only PCV13 or only PPV23 from 65 years old to June 30th, 2017. A multivariable logistic regression model was used to identify factors associated with pneumococcal vaccination series completion.ResultsA total of 224,132 adults were included in this study. Most received no pneumococcal vaccination (49%), while 34.3% received only one vaccine. Series completion occurred in 16.8% of adults. Some adults received only one vaccination: 11.6% received PPV23 and 22.7% received PCV13. The mean time between vaccinations was 420.8 days (approximately 14 months) for the PCV-PPV23 series, and 595.5 days (approximately 20 months) for the PPV23-PCV13 series. Adults were significantly more likely to complete pneumococcal vaccination series if they had at least one doctor’s office, outpatient visit, or pharmacy visit versus no visits, or received an influenza vaccination in the first year after turning 65 years than those who did not (All: P < 0.001).ConclusionDespite the 2014 recommendation, percentages of pneumococcal vaccination series completion were found to be low, aligning with recent literature. This highlights the need to improve series completion, given the increased risk and associated economic burden of pneumococcal disease in adults aged ≥65 years.     

Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly

BackgroundHerd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older in the period 2008–2013.MethodsThis is a post hoc analysis of two prospective studies from the Netherlands. Serotype specific urinary antigen detection and routine microbiological testing were used to categorize episodes as IPD or non-IPD PCAP caused by 7-valent pneumococcal conjugate vaccine (PCV7), PCV10-7 (three additional PCV10 serotypes), PCV13-10 (three additional PCV13 serotypes), and non-PCV13 serotypes. Proportions per vaccine-serotype group were assessed per year from June 1st to May 31st. Time trends were compared to national IPD data.ResultsOf 270 non-IPD PCAP episodes with known serotype, PCV7 serotypes decreased from 28% in 2008/2009 to 7% in 2012/2013 (p-value for trend <0.001). No change in PCV10-7 (19% overall) and PCV13-10 (29% overall) serotypes was observed. Non-PCV13 serotypes increased from 30% in 2008/2009 to 37% in 2012/2013 (p-value for trend 0.048). Trends corresponded with national IPD data.ConclusionPCV7 serotypes declined in non-IPD PCAP among elderly between 2008 and 2013, comparable to IPD data. No reduction in the additional PCV10 serotypes could be demonstrated within the first two years after PCV10 introduction.     

Impact of the pediatric 13-valent pneumococcal conjugate vaccine on serotype distribution and clinical characteristics of pneumococcal pneumonia in adults: The Japan Pneumococcal Vaccine Effectiveness Study (J-PAVE)

BackgroundThe pediatric 13-valent pneumococcal conjugate vaccine (PCV13) was included in the pediatric immunization programme in Japan in late 2013. The impact of vaccination on the serotype distribution and clinical characteristics of pneumococcal pneumonia has not been described.MethodsThe first phase of this multicentre prospective study was conducted at community-based hospitals in Japan from 2011 to 2014. The second phase was conducted from 2016 to 2017. Pneumococcal isolates and clinical data were collected from patients with community-acquired pneumonia who were ≥15 years of age. Patients were classified by pneumococcal serotype to PCV13 serotype, 23-valent pneumococcal polysaccharide vaccine (PPV23) non-PCV13 serotype, and non-vaccine serotype.ResultsA total of 484 patients were enrolled, 241 in the first phase and 243 in the second. The proportion of PCV13 serotypes decreased from 53% to 33% (p < 0.001), whereas PPV23 non-PCV13 serotypes did not change (p = 0.754). PCV13 serotypes were associated with increased risk of elevated blood urea nitrogen (adjusted odds ratio 2.49; 95% confidence interval: 1.49–4.16) and hospitalization (adjusted odds ratio 1.74; 95% confidence interval: 1.02–2.95). These associations were not observed in patients with PPV23 non-PCV13 serotypes.ConclusionsThe occurrence of pneumococcal pneumonia caused by vaccine-covered serotypes dramatically decreased following the introduction of pediatric PCV13. The PCV13 serotypes were associated with pneumonia severity.     

Pneumococcal polysaccharide vaccine is a cost saving strategy for prevention of acute coronary syndrome

ObjectiveThere is evidence that the pneumococcal polysaccharide vaccine (PPV) may reduce cardiovascular disease. We aimed to evaluate the cost-effectiveness of PPV for primary prevention of acute coronary syndrome (ACS) in the elderly in Australia.MethodsA Markov model was developed to investigate the costs, QALYs and ICERs of PPV administration in those aged ≥65 years without a history of ACS from the perspective of Australian healthcare system, using elderly-specific clinical data and local costs from Australian Heart Foundation and Australian Institute of Health and Welfare databases. A ten-years horizon was used, and all costs and health outcomes were discounted at 5% annually. The impact of various assumptions was tested with sensitivity analyses.ResultsIn the base-case analysis, interventional strategy (100% PPV coverage) prevented an additional five incident ACS events among 1000 “healthy” elderly individuals compared with standard of care (50% PPV coverage) over 10 years. 100% PPV was the dominant strategy, resulting in a QALY gain of 0.0075 and cost saving of AU$ 179 per person. The results were most sensitive to effectiveness of PPV at preventing ACS and reducing hospital bed-days, and cost of ACS admission, but in all sensitivity analyses 100% PPV remained the dominant strategy. Shortening the time horizon from ten to five years resulted in further cost saving.ConclusionPPV for the prevention of ACS in those aged ≥65 is a dominant intervention strategy, with cost saving and minor improvements in QALY. Healthcare providers should promote PPV administration for all eligible populations.     

Predictors of pneumococcal vaccination among Australian adults at high risk of pneumococcal disease

BackgroundAlthough nearly all Australian children are vaccinated against pneumococcal disease, pneumococcal vaccine uptake is low among high-risk adults. This study aimed to identify perceived barriers to pneumococcal vaccination among high-risk adults.MethodsThis paper reports combined data on pneumococcal vaccination collected from three different online, cross-sectional surveys that were administered in Australia between August 2019 and September 2020. Using Poisson regression, we identified characteristics and beliefs associated with self-reported pneumococcal vaccination among adults aged 65 and over or with chronic health conditions.ResultsThe weighted estimate for pneumococcal vaccine coverage was 24% for high-risk adults under 65 and 53% for adults aged 65 and over. Nearly half of those under 65 reported they had never heard of the pneumococcal vaccine, while 26% of those aged 65 and over had never heard of the vaccine. Among those under 65, pneumococcal vaccination was associated with high perceived disease susceptibility (PR = 1.97, 95% CI: 1.23, 3.18), not having heard of the pneumococcal vaccine (PR = 0.44, 95% CI: 0.28–0.69), awareness that their chronic health condition puts them at increased risk of pneumonia (PR = 2.44, 95% CI: 1.51–3.98), and having a doctor recommend the vaccine (PR = 3.02, 95% CI: 2.05–4.44). Among adults aged 65 and over, self-reported pneumococcal vaccination was associated with influenza vaccination in the previous 12 months (PR = 4.28, 95% CI: 2.85–6.44) and awareness that they are eligible for free pneumococcal vaccination (PR = 5.02, 95% CI: 2.34–10.77).ConclusionAwareness of pneumococcal vaccines was low among adults at high risk of pneumococcal disease, which appears to be contributing to low vaccine uptake. A doctor’s recommendation was associated with increased uptake of pneumococcal vaccine, so interventions should be developed to promote pneumococcal vaccine uptake in GP practices.     

Burden of four vaccine preventable diseases in older adults

BackgroundImplementation of additional targeted vaccinations to prevent infectious diseases in the older adults is under discussion in different countries. When considering the added value of such preventive measures, insight into the current disease burden will assist in prioritization. The aim of this study was derive the first estimates of the disease burden in adults aged 50 years or over in the Netherlands for influenza, pertussis, pneumococcal disease and herpes zoster.MethodsThe average annual disease burden for these four diseases in the Netherlands was calculated for the period 2010–2013 using the disability-adjusted life years (DALY) measure. Disease models and parameters were obtained from previous research. Where possible we adapted these models specifically for older adults and applied age-specific parameters derived from literature. The disease burden based on these adapted models and parameters was compared with the disease burden based on the general population models.ResultsThe estimated average annual disease burden was from high to low: pneumococcal disease (37,223 DALYs/year), influenza (7941 DALYs/year), herpes zoster (942 DALYs/year), and pertussis (812 DALYs/year). The adaptation of models and parameters specifically for the elderly resulted in a higher disease burden compared to the use of general population models.ConclusionsAmong older adults, the disease burden in the period 2010–2013 was highest for pneumococcal disease, mostly because of high mortality, followed by influenza. Disease burden of herpes zoster and pertussis was relatively low and consisted mostly of years lived with disability. Better information on the course of infectious diseases and long-term consequences would enable more accurate estimation of disease burden in older adults.     

Incremental effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia hospitalisation among Australian Indigenous children: A record linkage study

BackgroundThe impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18–24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation.MethodsIndigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders.Results11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87–1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16–1.35) and specified (HR 0.89; 95% CI: 0.49–1.62) from unspecified causes (HR 1.13; 95% CI: 0.86–1.49). During the baseline period before PPV23 vaccination (12–18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30–2.28).ConclusionIn this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18–30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.     

Adjuvant system AS02V enhances humoral and cellular immune responses to pneumococcal protein PhtD vaccine in healthy young and older adults: Randomised,controlled trials

BackgroundThe protection elicited by polysaccharide pneumococcal vaccines against community-acquired pneumonia in older adults remains debatable. Alternative vaccine targets include well-conserved pneumococcal protein antigens, such as pneumococcal histidine triad protein D (PhtD).ObjectiveTo evaluate humoral and cellular immune responses and safety/reactogenicity following immunisation with PhtD vaccine with or without adjuvant (alum or AS02_V) in older (≥65 years) and young (18–45 years) healthy adults.MethodsTwo phase I/II, single-blind, parallel-group studies were conducted in 150 older and 147 young adults. Participants were randomised to receive 2 doses (months 0 and 2) of PhtD 30 μg, PhtD 10 μg plus alum, PhtD 30 μg plus alum, PhtD 10 μg plus AS02_V or PhtD 30 μg plus AS02_V, or the 23-valent polysaccharide pneumococcal vaccine (23PPV) at month 0 with placebo (saline solution) at month 2. Safety/reactogenicity was assessed. PhtD-specific antibody, T cell and memory B cell responses were evaluated.ResultsSolicited adverse events were more common in young participants and with adjuvanted vaccines. No vaccine-related serious adverse events were reported. Although anti-PhtD geometric mean antibody concentrations (GMCs) were consistently lower in the older adult cohort than in young adults, GMCs in the older cohort following PhtD 30 μg plus AS02_V were comparable to those induced by plain PhtD or PhtD 30 μg plus alum in the young cohort. Compared with alum adjuvant, AS02_V adjuvant system was associated with an increased frequency of PhtD-specific CD4 cells in both cohorts and a significantly higher specific memory B cell response in the older cohort, similar to responses obtained in the young cohort.ConclusionThe improved immune response to PhtD vaccine containing the AS02_V adjuvant system in comparison to alum suggests that the reduced immune response to vaccines in older adults can be partially restored to the response level observed in young adults. ClinicalTrials.gov identifiers: NCT00307528/NCT01767402.     

Immunological responses to pneumococcal vaccine in frail older people

Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone.     

Considerations for developing an immunization strategy with enterovirus 71 vaccine

Enterovirus 71 (EV71) is a common pathogen for hand, foot, and mouth disease (HFMD), which has significant morbidity and mortality, and for which children aged 6–59 months age are at highest risk. Due to lack of effective treatment options, control of EV71 epidemics has mainly focused on development of EV71 vaccines. Clinical trials have been completed on 3 EV71 vaccines, with trial results demonstrating good vaccine efficacy and safety. When EV71 vaccine is approved by China's national regulatory authority, an evidence-based strategy should be developed to optimize impact and safety. An immunization strategy for EV71 vaccine should consider several factors, including the target population age group, the number of doses for primary immunization, the need for a booster dose, concomitant administration of other vaccines, economic value, program capacity and logistics, and public acceptance. Once EV71 vaccines are in use, vaccine effectiveness and safety must be monitored in large populations, and the epidemiology of HFMD must be evaluated to assure a match between vaccination strategy and epidemiology. Evaluation in China is especially important because there are no other EV71 vaccines globally.     

Pneumococcal antibodies in a child with type 14 pneumococcal conjugate vaccine failure

We measured the concentration, opsonic activity, and avidity of serotype-specific serum antibodies in a pneumococcal conjugate vaccine (PnCRM7) efficacy trial participant who contracted serotype 14 pneumococcal bacteremia following dose 3 of PnCRM7. Controls included 18 PnCRM7- and 10 MnCC-vaccinated children without invasive pneumococcal disease (IPD). The child with vaccine failure had 4.98 mcg/mL of serotype 14 antibodies 10 days before disease onset; these antibodies had greater opsonic activity and lower avidity than those of control PnCRM7 recipients. The child had no booster response to a fourth dose of PnCRM7 for most vaccine serotypes. We conclude that antibody concentration, functional activity and avidity do not predict individual protection against IPD, and immunological correlates of protection are only useful at the population level.