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.
SourceAvailable from: Agnieszka Mastalerz-Migas[Show abstract] [Hide abstract]
ABSTRACT: The influenza virus is one of the most common causes of viral respiratory tract infections. Some chronic diseases predispose to a severe course of the disease and increase the risk of complications and death. To minimize the risk of infection and complications, care of patients with increased risk should include prophylactic measures such as the administration of a seasonal influenza vaccine. An influenza vaccine is the best and cheapest method of influenza prevention. It is indicated for patients with chronic kidney disease, both during conservative treatment and renal replacement therapy. Many studies that have assessed the efficacy of an influenza vaccine in patients on hemodialysis have found that immune deficiency predisposes these patients to infection and a severe course of the disease. Because the immune response to a standard influenza vaccine in this population is weak, the studies covered many aspects of vaccination, including the need for a booster dose. Unlike in a healthy population, the efficacy of an influenza vaccine in patients on hemodialysis might be insufficient; however, the vaccine is still able to induce immunity in a significant number of patients. Considering the latest data and the results of studies described above, the recommendation of a seasonal influenza vaccine should be obligatory in all hemodialysis patients. This paper is based on original articles available from Medline database. The most recent and most significant literature on the influenza vaccine in patients on hemodialysis has been reviewed.Medical science monitor: international medical journal of experimental and clinical research 11/2013; 19:1013-8. DOI:10.12659/MSM.889671 · 1.22 Impact Factor
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ABSTRACT: Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HTâ„¢ was compared to Freundâ€™s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HTâ„¢ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freundâ€™s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.PLoS ONE 07/2013; 8(7-7):e68895. DOI:10.1371/journal.pone.0068895 · 3.53 Impact Factor
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ABSTRACT: Evidence regarding the mortality rate after administration of the pandemic influenza A (H1N1) 2009 vaccine on patients with underlying diseases is currently scarce. We conducted a case-control study in Japan to compare the mortality rates of patients with idiopathic interstitial pneumonia after the vaccines were administered and were not administered. Between October 2009 and March 2010, we collected clinical records in Japan and conducted a 1∶1 matched case-control study. Patients with idiopathic interstitial pneumonia who died during this period were considered case patients, and those who survived were considered control patients. We determined and compared the proportion of each group that received the pandemic influenza A (H1N1) 2009 vaccine and estimated the odds ratio. Finally, we conducted simulations that compensated for the shortcomings of the study associated with adjusted severity of idiopathic interstitial pneumonia. The case and control groups each comprised of 75 patients with idiopathic interstitial pneumonia. The proportion of patients who received the pandemic influenza A (H1N1) 2009 vaccine was 30.7% and 38.7% for the case and control groups, respectively. During that winter, the crude conditional odds ratio of mortality was 0.63 (95% confidence interval, 0.25-1.47) and the adjusted conditional odds ratio was 1.18 (95% confidence interval, 0.33-4.49); neither was significant. The simulation study showed more accurate conditional odds ratios of 0.63-0.71. In our study, we detected no evidence that the influenza A (H1N1) 2009 vaccine increased the mortality rate of patients with idiopathic interstitial pneumonia. The results, however, are limited by the small sample size and low statistical power. A larger-scale study is required.PLoS ONE 02/2014; 9(2):e88927. DOI:10.1371/journal.pone.0088927 · 3.53 Impact Factor