thymalfasin and Influenza--Human

Influenza constitutes a serious problem for healthcare and social services worldwide, owing to its pattern and the severity of its complications in some categories of subjects at risk, such as the elderly and immunocompromised individuals. The only really effective means of combating influenza is vaccination. The elderly and immunocompromised subjects are refractory or low responders to vaccination. The need for ever more immunogenic and efficacious influenza vaccines, especially for subjects at risk, has prompted the development of adjuvated vaccines. With a view to enhancing the immune response in the elderly and in subjects at risk, the possibility of co-administering immunostimulants as Thymosin alpha-1 (Talpha1) with influenza vaccines has been investigated. Talpha1 is a biologically active peptide made up of 28 amino acids that can enhance T-cells, dendritic cell and antibody responses, modulate cytokines and chemokines production. Several studies were conducted and showed that Talpha1 ameliorate the performanc of influenza vaccination in elderly and subjects at risk. Although further studies on co-adjuvants are necessary, the future prospects of producing ever more efficacious influenza vaccines appear very promising.

Topics: Adjuvants, Immunologic; Humans; Influenza Vaccines; Influenza, Human; Thymalfasin; Thymosin

From a clinical perspective, the immune deficiency of aging (immune senescence) is not profound. In fact, it may be of little clinical consequence. However, older people are prone to chronic and debilitating disorders which alone, or in concert with the medications used in their treatment, may add to the age effect and create a more clinically relevant immune deficiency. As a result, many older people are susceptible to infection. Furthermore, it is now well recognized that older people respond less well to immunization protocols. Protection against influenza by vaccination with hemagluttinin is the prototype example. Despite programs that have raised vaccination rates dramatically over the past three decades, influenza remains a major cause of morbidity and mortality in the elderly. This, in part, is due to the fact that vaccine responses are reduced in older recipients. Strategies are under development to enhance vaccine efficacy in this population and one such strategy is the adjuvant use of thymosin alpha 1 (Talpha1). In both animal experiments and human trials, there has been demonstrated enhancement of vaccine responses. The findings to date warrant additional efforts to further examine the role of Talpha1 in augmenting specific vaccine responses both in the elderly or in younger subjects in situations in which there are suboptimal quantities of immunizing antigen available.

Topics: Aged; Combined Modality Therapy; Drug Administration Schedule; Humans; Influenza Vaccines; Influenza, Human; Male; Placebos; Thymalfasin; Thymosin

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.. 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.. 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.. 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.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Neutralizing; Antibodies, Viral; Female; Humans; Immunoassay; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Pilot Projects; Renal Dialysis; Thymalfasin; Thymosin; Uremia; Young Adult