Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands

BackgroundThe long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the impact of PCVs on community-acquired pneumonia (CAP) hospitalization rates in all age-groups.MethodsA time series analysis using Poisson regression was performed on 155,994 CAP hospitalizations. Hospitalization rates were calculated using the total number of hospitalizations as denominator. The time trend in the pre-PCV period (1999–2006) was extrapolated to predict the hospitalization rate in the post-PCV period (2006–2014) if PCV had not been implemented. Rate ratios over time were calculated by comparing observed and predicted time trends.ResultsIn children <5 years of age, the observed hospitalization rates during the post-PCV period were significantly lower than predicted if PCV had not been implemented (0–6 months: 0.62, 95% CI: 0.41–0.96; 6 months – 1 year: 0.67, 95% CI: 0.50–0.90; 2–4 years: 0.78, 95% CI: 0.61–0.97). In all other age-groups, rate ratios declined over time but did not reach statistical significance.ConclusionsAfter introduction of PCV, CAP hospitalizations declined in young children but no clear impact of PCV on CAP hospitalizations was seen in other age-groups.     

Asthma exacerbations among asthmatic children receiving live attenuated versus inactivated influenza vaccines

ObjectiveTo investigate whether there is a difference in the risk of asthma exacerbations between children with pre-existing asthma who receive live attenuated influenza vaccine (LAIV) compared with inactivated influenza vaccine (IIV).Material and methodsWe identified IIV and LAIV immunizations occurring between July 1, 2007 and March 31, 2014 among Kaiser Permanente Northern California members aged 2 to <18 years with a history of asthma, and subsequent asthma exacerbations seen in the inpatient or Emergency Department (ED) setting. We calculated the ratio of the odds (OR) of an exacerbation being in the risk interval (1–14 days) versus the comparison interval (29–42 days) following immunization, separately for LAIV and IIV, and then examined whether the OR differed between children receiving LAIV and those receiving IIV (“difference-in-differences”).ResultsAmong 387,633 immunizations, 85% were IIV and 15% were LAIV. Children getting LAIV vs. IIV were less likely to have “current or recent, persistent” asthma (25% vs. 47%), and more likely to have “remote history” of asthma (47% vs. 25%). Among IIV-vaccinated asthmatic children, the OR of an inpatient/ED asthma exacerbation was 0.97 (95% CI: 0.82–1.15). Among LAIV-vaccinated asthmatic children the OR was 0.38 (95% CI: 0.17–0.90). In the difference-in-differences analysis, the odds of asthma exacerbation following LAIV were less than IIV (Ratio of ORs: 0.40, CI: 0.17–0.95, p value: 0.04).ConclusionAmong children ≥2 years old with asthma, we found no increased risk of asthma exacerbation following LAIV or IIV, and a decreased risk following LAIV compared to IIV.     

Pre-vaccine plasma levels of soluble inflammatory indices negatively predict responses to HAV,HBV, and tetanus vaccines in HCV and HIV infection

BackgroundChronic hepatitis C virus (HCV) and HIV infections are associated with impaired responses to neo-antigens contained in hepatitis A virus (HAV)/hepatitis B virus (HBV) vaccines, yet responsible mechanisms are unclear.MethodsACTG 5232 and CFAR0910 were clinical trials where pre-vaccine levels of plasma IP10, IL-6, sCD163 and sCD14 were measured in viremic HCV- (n = 15) or HIV-infected participants (n = 24) and uninfected controls (n = 10). Accelerated dosing HAV/HBV vaccine and tetanus booster were administered and antibody response was measured at 0, 1, 3, 8, and 24 weeks.ResultsPre-vaccine plasma IP10, IL-6, and sCD14 levels were elevated in both HCV and HIV-infected participants, while sCD163 was also elevated in HCV-infected participants. Pre-immunization tetanus antibody levels were lower in HIV-infected than in uninfected participants, while vaccine induced antibody responses were intact in HCV and HIV-infected participants. After HAV/HBV vaccination, HCV and HIV-infected participants had lower and less durable HAV and HBV antibody responses than uninfected controls.Among HCV-infected participants, pre-vaccine plasma IP10, IL-6, sCD14, and sCD163 levels inversely correlated with HAV, HBV and tetanus antibody responses after vaccine. Low HAV/HBV vaccine responses in HIV-infected participants prohibited assessment of immune correlates.ConclusionsDuring HCV and HIV infection markers of systemic inflammation reflect immune dysfunction as demonstrated by poor response to HAV/HBV neo-antigen vaccine.     

Multifaceted characterization of recombinant protein-based vaccines: An immunochemical toolbox for epitope-specific analyses of the hepatitis E vaccine

The integrity of functional epitopes is a critical quality attribute for recombinant protein based vaccines since the presence of these native-like epitopes is the structural basis for vaccines to elicit functional antibodies. To demonstrate the quality and quantity of functional epitopes on vaccine antigens, a toolbox of assessing antigen characteristics is essential. Among the physicochemical, biophysical, immunochemical and in vivo potency analyses, the epitope-specific assays are most critical assessment of the antigen functionality. In this study, we used hepatitis E virus vaccine as an example to illustrated how the monoclonal antibody (mAb) based immunochemical assays were established for in-depth and multifaceted antigen characterization. A large panel of mAbs were developed and characterized using epitope clustering analysis. A subset of these mAbs recognizing non-overlapping epitopes were chosen to be used for assay development. Orthogonal methods, including surface plasma resonance-based BIAcore, solution competitive ELISA and sandwich ELISA, were developed for the antigenicity assessment. The sandwich ELISA with a pair of mAbs, recognizing two different epitopes, was used to assess the accelerated antigen stability, showing enhanced stability with adjuvant adsorption. Such a sandwich ELISA with robust performance has the potentials to be used for in vitro potency analysis to replace animal-based potency assay as product release test. In summary, using hepatitis E vaccine as an example, we demonstrated the importance and establishment of a mAb-based immunochemical toolbox for multifaceted antigen characterization. This is particularly important to demonstrate the successful reconstruction of the native-like and functional epitopes on a recombinant antigen post expression and purification. These epitope-specific and multifaceted assays serve as critical tools for process monitoring or lot consistency tests in support of vaccine development and manufacturing.     

Influenza vaccine effectiveness among patients with high-risk medical conditions in the United States, 2012–2016

BackgroundAnnual influenza vaccination has been recommended for persons with high-risk conditions since the 1960s. However, few estimates of influenza vaccine effectiveness (VE) for persons with high-risk conditions are available.MethodsData from the U.S. Influenza Vaccine Effectiveness Network from 2012 to 2016 were analyzed to compare VE of standard-dose inactivated vaccines against medically-attended influenza among patients aged ≥6 months with and without high-risk medical conditions. Patients with acute respiratory illness were tested for influenza by RT-PCR. Presence of high-risk conditions and vaccination status were obtained from medical records. VE by influenza virus type/subtype and age group was calculated for patients with and without high-risk conditions using the test-negative design. Interaction terms were used to test for differences in VE by high-risk conditions.ResultsOverall, 9643 (38%) of 25,369 patients enrolled during four influenza seasons had high-risk conditions; 2213 (23%) tested positive for influenza infection. For all ages, VE against any influenza was lower among patients with high-risk conditions (41%, 95% CI: 35–47%) than those without (48%, 95% CI: 43–52%; P-for-interaction = 0.02). For children aged <18 years, VE against any influenza was 51% (95% CI: 39–61%) and 52% (95% CI: 39–61%) among those with and without high-risk conditions, respectively (P-for-interaction = 0.54). For adults aged ≥18 years, VE against any influenza was 38% (95% CI: 30–45%) and 44% (95% CI: 38–50%) among those with and without high-risk conditions, respectively (P-for-interaction = 0.21). For both children aged <18 and adults aged ≥18 years, VEs against illness related to influenza A(H3N2), A(H1N1)pdm09, and influenza B virus infection were similar among those with and without high-risk conditions.ConclusionsInfluenza vaccination provided protection against medically-attended influenza among patients with high-risk conditions, at levels approaching those observed among patients without high-risk conditions. Results from our analysis support recommendations of annual vaccination for patients with high-risk conditions.     

Core pertussis transmission groups in England and Wales: A tale of two eras

The recent resurgence of pertussis in England and Wales has been marked by infant deaths and rising cases in teens and adults. To understand which age cohorts are most responsible for these trends, we employed three separate statistical methods to analyze high-resolution pertussis reports from 1982 to 2012. The fine-grained nature of the time-series allowed us to describe the changes in age-specific incidence and contrast the transmission dynamics in the 1980s and during the resurgence era. Our results identified infants and school children younger than 10 years of age as a core group, prior to 2002: pertussis incidence in these populations was predictive of incidence in other age groups. After 2002, no core groups were identifiable. This conclusion is independent of methodology used. Because it is unlikely that the underlying contact patterns substantially changed over the study period, changes in predictability likely result from the introduction of more stringent diagnostics tests that may have inadvertently played a role in masking the relative contributions of core transmission groups.