title: Thymosin-alpha 1 (Zadaxin) enhances the immunogenicity of an adjuvated pandemic H1N1v influenza vaccine (Focetria) in hemodialyzed patients: a pilot study.
abstract: BACKGROUND
  Although influenza vaccination is widely recommended for immunosuppressed people, the same immune dysfunction that can increase the risk of contracting influenza might also compromise vaccine effectiveness, especially during pandemics. Clinical data have highlighted the role of adjuvants in improving vaccine efficacy. As uremic patients are especially vulnerable to infections, it is recommended that they should be vaccinated yearly against influenza. This paper presents the results of a pilot clinical trial, conducted in hemodialyzed patients with an adjuvated pandemic H1N1v influenza vaccine alone and combined with Thymosin-alpha 1.
  
  
  METHODS
  Subjects were subdivided into 3 treatment groups receiving: the adjuvated pandemic influenza vaccine (Focetria) only (first treatment group), and the Vaccine+Thymosin alpha 1 (Zadaxin) at a dose of 3.2 and 6.4 mg (second and third treatment groups respectively). The immunoresponse was assessed on days 0, 21, 42, 84 and 168 after vaccine administration by means of Hemagglutination Inhibition (HI), Microneutralization (MN) and Single Radial Hemolysis (SRH) assays. The CHMP regards HI as the gold standard test to evaluate the immune response to influenza vaccines before influenza vaccines are licensed. The CHMP criteria are slightly different in adults (18-60-year-old subjects) and the elderly (>60 years old). Indeed, 40% of seroconversion, 70% of subjects seroprotected 21 days after vaccination, and a 2.5-fold increase in GMR (Geometric Mean Ratio) are required in adults, while in the elderly, the corresponding threshold values are: 30%, 60% and a 2-fold increase. All these criteria must be met for the licensing of a pandemic influenza vaccine. Safety evaluation was performed by means of Adverse Event (AE) recording, laboratory assays (hematology and chemistry), electrocardiogram, and assessment of vital signs.
  
  
  RESULTS
  Three populations were considered: Intention-To-Treat (ITT) (94 patients), Per Protocol (PP) (82 patients), and Safety population (99 patients). With regard to the Geometric Mean Titer (GMT) and the Geometric Mean Ratio (GMR) of HI on Day 21 in the ITT population, both "Vaccine+Thymosin alpha 1" groups presented better results than the "Vaccine only" group. A large proportion of ITT patients in the two Vaccine+Thymosin alpha 1 groups achieved seroconversion by Day 21. On Day 42, the decrease in the GMT of HI was greater in the Vaccine+Thymosin alpha 1 groups than in the vaccine only group. Similar results were obtained in the PP population. The CHMP criteria were fully met in the groups treated with Vaccine+Thymosin alpha 1. No AE was found to be related to Thymosin alpha 1 nor to the Focetria vaccine.
  
  
  CONCLUSIONS
  Although further studies in larger hemodialyzed populations are necessary, it can be concluded that Thymosin alpha 1 enhanced the immunogenicity of the pandemic influenza vaccine used. Moreover, it proved safe and well tolerated, and did not affect hematology or blood-chemistry values.
authors.affiliation: Second Division of Nephrology and Dialysis - Padua Hospital, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Carraro
authors.forename: A
authors.initials: A
authors.lastname: Naso
authors.forename: E
authors.initials: E
authors.lastname: Montomoli
authors.forename: R
authors.initials: R
authors.lastname: Gasparini
authors.forename: R
authors.initials: R
authors.lastname: Camerini
authors.forename: D
authors.initials: D
authors.lastname: Panatto
authors.forename: M C
authors.initials: MC
authors.lastname: Tineo
authors.forename: L
authors.initials: L
authors.lastname: De Giorgi
authors.forename: S
authors.initials: S
authors.lastname: Piccirella
authors.forename: B
authors.initials: B
authors.lastname: Khadang
authors.forename: M
authors.initials: M
authors.lastname: Ceracchi
authors.forename: A
authors.initials: A
authors.lastname: De Rosa
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006801:Humans; D007118:Immunoassay; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D006435:Renal Dialysis; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D014511:Uremia / Q000276:immunology / Q000628:therapy; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C558220:focetria; D013947:Thymosin; D000077596:Thymalfasin