Risk factors affecting seroconversion after influenza A/H1N1 vaccination in hemodialysis patients

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Abstract

Abstracts

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.

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Most cited references 26

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Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines.

M Saurwein-Teissl, Walther Parson, Emanuelle Trannoy … (2002)

Although it is generally recognized that the function of the immune system declines with age, the nature of the underlying defects is still poorly understood. We now demonstrate the predominance of CD8(+)CD28(-) T cell clonal expansions in elderly persons who fail to produce specific Abs following influenza vaccination. These clones express effector cell markers and are mostly CD45RA(+). When isolated and put into culture, they are unable to proliferate, but produce IFN-gamma (but no IL-5) upon stimulation with anti-CD3 or autoantigen. These autoreactive CD8(+) type 1 effector cells seem to trigger a Th1 polarization, as CD4(+) T cells from elderly persons without in vivo Ab production produce Th1, but only low amounts of Th2 cytokines upon in vitro stimulation with PHA. Therefore, the increased occurrence of CD8(+)CD28(-) clonal expansions may be decisive for the development of immune deficiency in the elderly.

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Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine.

Tristan W. Clark, Manish Pareek, Katja Hoschler … (2009)

The 2009 pandemic influenza A (H1N1) virus has emerged to cause the first pandemic of the 21st century. Development of effective vaccines is a public health priority. We conducted a single-center study, involving 176 adults, 18 to 50 years of age, to test the monovalent influenza A/California/2009 (H1N1) surface-antigen vaccine, in both MF59-adjuvanted and nonadjuvanted forms. Subjects were randomly assigned to receive two intramuscular injections of vaccine containing 7.5 microg of hemagglutinin on day 0 in each arm or one injection on day 0 and the other on day 7, 14, or 21; or two 3.75-microg doses of MF59-adjuvanted vaccine, or 7.5 or 15 microg of nonadjuvanted vaccine, administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay and a microneutralization assay on days 0, 14, 21, and 42 after injection of the first dose. The most frequent local and systemic reactions were pain at the injection site and muscle aches, noted in 70% and 42% of subjects, respectively; reactions were more common with the MF59-adjuvanted vaccine than with nonadjuvanted vaccine. Three subjects reported fever, with a temperature of 38 degrees C or higher, after either dose. Antibody titers, expressed as geometric means, were higher at day 21 among subjects who had received one dose of MF59-adjuvanted vaccine than among those who had received one dose of nonadjuvanted vaccine (P<0.001 by the microneutralization assay). By day 21, hemagglutination-inhibition and microneutralization antibody titers of 1:40 or more were seen in 77 to 96% and 92 to 100% of subjects receiving MF59-adjuvanted vaccine, respectively, and in 63 to 72% and 67 to 76% of those receiving nonadjuvanted vaccine, respectively. By day 42, after two doses of vaccine, hemagglutination-inhibition and microneutralization antibody titers of 1:40 or more were seen in 92 to 100% and 100% of recipients of MF59-adjuvanted vaccine, respectively, and in 74 to 79% and 78 to 83% of recipients of nonadjuvanted vaccine, respectively. Monovalent 2009 influenza A (H1N1) MF59-adjuvanted vaccine generates antibody responses likely to be associated with protection after a single dose is administered. (ClinicalTrials.gov number, NCT00943358). Copyright 2009 Massachusetts Medical Society

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A novel influenza A (H1N1) vaccine in various age groups.

Han Fang, Suzette Peng, Chang-gui Li … (2009)

There is an urgent need for a vaccine that is effective against the 2009 pandemic influenza A (H1N1) virus. A split-virus, inactivated candidate vaccine against the 2009 H1N1 virus was manufactured, and we evaluated its safety and immunogenicity in a randomized clinical trial. Subjects were between 3 and 77 years of age, stratified into four age groups. The immunization schedule consisted of two vaccinations, 21 days apart. Subjects were injected with placebo or with vaccine, with or without alum adjuvant, at doses of 7.5 microg, 15 microg, or 30 microg. Serologic analysis was performed at baseline and on days 21 and 35. A total of 2200 subjects received one dose, and 2103 (95.6%) received the second dose, of vaccine or placebo. No severe adverse side effects associated with the vaccine were noted. In the nonadjuvanted-vaccine groups, injection-site or systemic reactions, most mild in nature, were noted in 5.5 to 15.9% of subjects. Among the subjects receiving 15 microg of nonadjuvanted vaccine, a hemagglutination-inhibition titer of 1:40 or more was achieved by day 21 in 74.5% of subjects between 3 and 11 years of age, 97.1% of subjects between 12 and 17 years, 97.1% of subjects between 18 and 60 years, and 79.1% of subjects 61 years of age or older; by day 35, the titer had been achieved in 98.1%, 100%, 97.1%, and 93.3% of subjects, respectively. The proportion with a titer of 1:40 or more was generally highest among the subjects receiving 30 microg of vaccine, with or without adjuvant. Vaccine without adjuvant was associated with fewer local reactions and greater immune responses than was vaccine with adjuvant. These data suggest that a single dose of 15 microg of hemagglutinin antigen without alum adjuvant induces a typically protective immune response in the majority of subjects between 12 and 60 years of age. Lesser immune responses were seen after a single dose of vaccine in younger and older subjects. (ClinicalTrials.gov number, NCT00975572).

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Author and article information

Contributors

Sung Jin Moon

Sang Hun Lee

Young-Ho Byun

Gi Young Yun

Seung Kyu Kim

Baik-Lin Seong

Ah Reum Kim

Eun sun Park

Hyung-Jong Kim

Jung Eun Lee

Sung Kyu Ha

Jae Myun Lee

Hyeong-Cheon Park

Journal

Journal ID (nlm-ta): BMC Nephrol

Journal ID (iso-abbrev): BMC Nephrol

Title: BMC Nephrology

Publisher: BioMed Central

ISSN (Electronic): 1471-2369

Publication date Collection: 2012

Publication date (Electronic): 3 December 2012

Volume: 13

Page: 165

Affiliations

[1 ]Myongji Hospital, College of Medicine, Kwandong University, Goyang, Korea

[2 ]Department of Internal Medicine, Gangnam Severance Hospital, Institute of Vascular and Metabolism Research, College of Medicine, Yonsei University, 146-92 Dogok-Dong, Gangnam-Gu, Seoul 135-720, Korea

[3 ]Department of Biotechnology, College of Life Science & Biotechnology, Yonsei University, Seoul, Korea

[4 ]Department of Microbiology and Brain Korea 21 Project for Medical Sciences, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, 134, Shinchon-dong, Seodaemoon-gu 120-752 Seoul, Korea

[5 ]BundangCHA Medical Center, CHA University, Sungnam, Korea

[6 ]Yongin Severance Hospital, College of Medicine, Yonsei University, Yongin, Korea

Article

Publisher ID: 1471-2369-13-165

DOI: 10.1186/1471-2369-13-165

PMC ID: 3560184

PubMed ID: 23206898

SO-VID: f4414abd-6816-4c0c-ba77-82db5bedbf06

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 20 May 2012

Date accepted : 28 November 2012

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Risk factors affecting seroconversion after influenza A/H1N1 vaccination in hemodialysis patients

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Abstract

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Karger: Nephrology

Most cited references 26

Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines.

Trial of 2009 influenza A (H1N1) monovalent MF59-adjuvanted vaccine.

A novel influenza A (H1N1) vaccine in various age groups.

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