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

Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
Vaccine (Impact Factor: 3.62). 05/2012; 30(33):5009-18. DOI: 10.1016/j.vaccine.2012.05.016
Source: PubMed


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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    • "Whilst traditional vaccination reduces influenza-associated mortality [13], it is least efficacious in the immunocompromised individuals who are most susceptible to complications and increased mortality [14], [15], and who include pregnant women [16]. Consequently, immunocompromised individuals make up the majority of the many thousands of annual influenza-related deaths [14], [17], which provides the rationale for passive immunotherapy as influenza prophylaxis or treatment in these individuals because additional time is not needed to generate an efficient vaccine-induced adaptive immune response [18]. "
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    PLoS ONE 07/2013; 8(7-7):e68895. DOI:10.1371/journal.pone.0068895 · 3.23 Impact Factor
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    • "Fulop et al. observed that non-response group after influenza vaccination in the elderly patients had lower nutritional parameters such as hemoglobin, total protein, iron, vitamin E, and DHEA [28]. Recent research by Chang et al. also suggested that hemoglobin level is a significant predictor for seroresponse and seroconversion in HD patients [19]. Our study did not have enough power to assess the influence of inflammatory or nutritional parameters on seroconversion. "
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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 · 1.69 Impact Factor
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    Journal of The Royal Society Interface 07/2012; 9(76):2798-803. DOI:10.1098/rsif.2012.0404 · 3.92 Impact Factor
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