Poor immune response to a standard single dose non-adjuvanted vaccination against 2009 pandemic H1N1 influenza virus A in the adult and elder hemodialysis patients
ABSTRACT Hemodialysis patients have higher risk of mortality and morbidity when infected with 2009 pandemic H1N1 (pH1N1/09) virus. Depending on different methodologies and criteria, previous studies reported variable response rates to adjuvanted vaccines against pH1N1/09 virus in hemodialysis patients, however, the efficacy of non-adjuvanted vaccines, which are currently used in many countries such as the USA and Asian areas, has not been comprehensively evaluated in hemodialysis population before.
We evaluated the efficacy of a standard single 15 μg-dose of non-adjuvanted monovalent pH1N1/09 vaccine (AdimFlu-S) in vaccine-naïve 110 hemodialysis and 173 healthy participants. When enrolling, all participants had not any clinical symptom or sign suggesting pH1N1/09 infection since the index case was identified in Taiwan. Sera from all participants were tested by hemagglutination inhibition (HI) and micro-neutralization-ELISA (microNT-ELISA) tests before and 21 days after vaccination. The outcome parameters were seroconversion rate (≥ 4-fold in HI titer with titer ≥ 1:40), seroprotection rate (HI titers ≥ 1:40), seroresponse rate (≥ 4-fold increase in HI or microNT-ELISA titer), fold of increase in geometric mean (GM) titers, and adverse effects.
In method A analyses, we included all participants' data in final analyses, and the seroconversion rates and the fold increase of GM titer after vaccination were 25.4% and 1.8 in adult (18-60-year olds) hemodialysis subgroup, and 23.4% and 1.8 in elder (>60-year olds) hemodialysis subgroup based on HI titers, which were all significantly lower than those of the corresponding healthy control subgroups. Similar trends were observed based on microNT-ELISA titers, further validating the results. Multivariable analysis revealed hemoglobin and cholesterol levels were significant predictors for seroresponse in hemodialysis patients, suggesting the possible impacts of nutrition status and anemia. In method B analyses, we excluded participants with pre-vaccination seroprotection (based on HI or microNT-ELISA criteria) in final analyses. The response rates in various subgroups from method B analyses were also similar as those from method A analyses. No severe adverse effect was noted.
According to the European and U.S. criteria, a single 15 μg-dose of non-adjuvanted pH1N1/09 vaccination is safe but ineffective in both adult and elder hemodialysis patients. Further studies using multiple doses or higher antigen amount are warrant to define the most appropriate regimen.
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ABSTRACT: Sizeable quantities of 2009 pandemic influenza A/H1N1 (H1N1pdm) vaccine in the USA became available at the end of 2009 when the autumn wave of the epidemic was declining. At that point, risk factors for H1N1-related mortality for some of the high-risk groups, particularly adults with underlying health conditions, could be estimated. Although those high-risk groups are natural candidates for being in the top priority tier for vaccine allocation, another candidate group is school-aged children through their role as vectors for transmission affecting the whole community. In this paper, we investigate the question of prioritization for vaccine allocation in a declining epidemic between two groups-a group with a high risk of mortality versus a 'core' group with a relatively low risk of mortality but fuelling transmission in the community. We show that epidemic data can be used, under certain assumptions on future decline, seasonality and vaccine efficacy in different population groups, to give a criterion when initial prioritization of a population group with a sufficiently high risk of epidemic-associated mortality is advisable over the policy of prioritizing the core group.Journal of The Royal Society Interface 07/2012; 9(76):2798-803. DOI:10.1098/rsif.2012.0404 · 3.86 Impact Factor
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ABSTRACT: BACKGROUND: Hemodialysis (HD) patients have multiple causes of immune dysfunction and poor immune response to influenza vaccination. We investigated the antibody response rate to a pandemic H1N1/2009 influenza vaccination and clinical parameters influencing the induction of antibody responses in HD patients. METHODS: A total of 114 HD patients were vaccinated with a monovalent adjuvanted H1N1 inactivated influenza vaccine. Titers of neutralizing antibodies were evaluated by hemagglutination inhibition (HI) assay at pre- and 4 weeks after vaccination. Seroconversion was defined as either a pre-vaccination HI titer < 1:10 and a post vaccination HI titer > 1:40 or a pre-vaccination HI titer >= 1:10 and a minimum four-fold rise in post-vaccination HI antibody titer. Seventeen out of 114 HD patients (14.9%) tested positive for antibodies against influenza A/H1N1/2009 before vaccination. The remaining 97 baseline sero-negative patients were included in the analysis. RESULTS: Only 30 (30.9%) HD patients had seroconversion 4 weeks after vaccination. The elderly patients, those over 65 years of age, showed significantly lower seroconversion rate compared to younger HD patients (20.5% vs. 39.6%, p = 0.042). Furthermore, patients with hemoglobin values less than 10 g/dL had a significantly lower seroconversion rate compared to those with higher hemoglobin values (20.0 vs. 38.6%, p = 0.049). By multivariate logistic regression analysis, only age >=65 years (OR = 0.336, 95% confidence interval (CI) 0.116-0.971, p = 0.044) and hemoglobin levels <10 g/dL (OR = 0.315, 95% CI 0.106-0.932, p = 0.037) were independently associated with seroconversion after vaccination. CONCLUSIONS: Our data show that HD patients, especially who are elderly with low hemoglobin levels, are at increased risk for lower seroconversion rate after influenza A/H1N1 vaccination. Further studies are needed to improve the efficacy of vaccination in these high risk patients.BMC Nephrology 12/2012; 13(1):165. DOI:10.1186/1471-2369-13-165 · 1.52 Impact Factor
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ABSTRACT: Infection is the second most common cause of death in patients with end-stage renal disease (ESRD), following cardiovascular causes. Immunization is a fairly simple, but underutilized, strategy for prevention of infectious morbidity and mortality in patients with kidney failure. It is imperative for nephrologists and primary care providers to have an understanding of immunization as an essential component of preventive healthcare measures in this high-risk population. Patients with ESRD represent a unique population due to their immunosuppressed state, dialysis-related exposures and suboptimal response to routine vaccines. While the Advisory Committee on Immunization Practices (ACIP) provides guidelines for vaccination of patients with renal disease against Hepatitis B, influenza and pneumococcal disease, the data on immunization against other commonly preventable infectious diseases are lacking. This article reviews the recent evidence on immunization in the ESRD population and synthesizes the related implications for maximizing prevention of infectious diseases in this high-risk population.Seminars in Dialysis 06/2013; 26(4). DOI:10.1111/sdi.12101 · 2.07 Impact Factor