Original Investigation
Dialysis
Immunogenicity and Efficacy in Hemodialysis Patients of an AS03A-Adjuvanted Vaccine for 2009 Pandemic Influenza A(H1N1): A Nonrandomized Trial

https://doi.org/10.1053/j.ajkd.2010.11.031Get rights and content

Background

Hemodialysis patients have a reduced response to vaccinations because of uremia-related immune dysfunction. To increase the immunogenicity of vaccines, antigens can be formulated with adjuvants. The new tocopherol-containing adjuvant system AS03A has not been tested yet in patients with end-stage renal disease.

Study Design

Nonrandomized trial.

Setting & Participants

291 hemodialysis patients from 3 dialysis units co-operating with the Department of Nephrology at the University Hospital Heidelberg, Germany: 169 patients were vaccinated using either 1 (64 patients) or 2 doses (105 patients); 123 patients refused the vaccination and served as controls.

Intervention

Intramuscular immunization with 3.75 μg of an inactivated split-virion A/California/7/2009 H1N1v pandemic vaccine adjuvanted with AS03A in a single- or double-dose regimen.

Outcomes

A pandemic influenza A immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) response >11 AU (arbitrary units) was defined as a positive response.

Measurements

Quantitative antibody testing using the pandemic influenza A IgG ELISA. Antibody titers were tested 3 months after vaccination and compared with nonimmunized dialysis patients.

Results

After vaccination against 2009 pandemic influenza A(H1N1), 41 of 64 (64.1%) patients with 1 vaccination and 93 of 105 (88.6%) with 2 vaccinations showed a protective immune response compared with 43 of 123 (34.9%) unvaccinated patients (P < 0.001). Logistic regression analysis confirmed vaccination dose as an independent factor for response to pandemic H1N1 vaccination. No episode of pandemic H1N1 illness occurred in any group within the study period of 6 months after vaccination. No serious adverse events occurred, and local symptoms ranged from mild to moderate in 143 of 169 (84.6%) patients.

Limitations

Nonrandomized assignment; use of nontreated patients as controls; no comparison to nonadjuvanted vaccines; dose variation in the intervention group.

Conclusions

Pandemic H1N1 vaccine adjuvanted with AS03A is immunogenic, effective, and safe in hemodialysis patients.

Section snippets

Study Design

The primary objective of this nonrandomized trial was to assess the efficacy and safety of AS03A-adjuvanted 2009 pandemic influenza A(H1N1) vaccination with 1 and 2 doses as analyzed using the Pandemic New Influenza A immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA; Genzyme Virotech, www.virotech.de) in long-term hemodialysis patients. Additional assessments included evaluation of the antipandemic H1N1 antibody titer in patients without vaccination and evaluation of an

Study Population

Altogether, 292 patients with end-stage renal disease receiving regular hemodialysis therapy (mean, 4.6 ± 0.4 hours) participated in this nonrandomized trial (171 men, 121 women; mean age, 68.8 ± 13.8 years; range, 28-92 years; Fig 1). Patient demographics for 169 patients with AS03A-adjuvanted pandemic H1N1 vaccination and 123 control patients without vaccination are listed in Table 1.

Unvaccinated Hemodialysis Patients

Long-term hemodialysis patients without pandemic H1N1 vaccination (control cohort) showed a wide range of IgG

Discussion

In this nonrandomized trial, we showed that AS03A-adjuvanted vaccination against 2009 pandemic influenza A(H1N1) is immunogenic and efficient in hemodialysis patients despite uremia-related immune dysfunction, with an acceptable safety profile. After a single dose of pandemic H1N1 vaccine, 41 of 64 (64.1%) hemodialysis patients showed a positive response compared with 98.2% of 130 healthy adults.15 These data suggest that a single dose is sufficient for immunizing healthy adults, which agrees

Acknowledgements

Support: The authors thank Genzyme Virotech for providing the Pandemic New Influenza IgG ELISA.

Financial Disclosure: The authors declare that they have no relevant financial interests.

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