Influenza Vaccination in Fibromyalgia Patients

• proportion of patients who achieve a titer of antibodies above 1/40, against each of the antigens included in the vaccine [ Time Frame: Six weeks ] [ Designated as safety issue: No ]
  

• Number of adverse events [ Time Frame: Six weeks ] [ Designated as safety issue: Yes ]
  The occurrence of vaccine - related adverse events (allergic reactions, pain at injection site, fever etc) will be documented.
  
  
• Clinical changes post - vaccination [ Time Frame: Six weeks ] [ Designated as safety issue: No ]
  Clinical evaluation of Fibromyalgia patients will be performed on follow up, including a tender point count and documentation of the Fibromyalgia severity scale.
  
  

Fifty patients with fibromyalgia and 30 healthy, age - matched controls will participate in the study.

The classification of fibromyalgia will be performed by applying the 1990 ACR criteria.

After signing informed consent, all subjects will be vaccinated with the inactivated split virion vaccine, recommended by the WHO this fall.

Patients will be evaluated at weeks 0 and 6 weeks later. Clinical evaluation will be based on the Fibromyalgia Impact Questionnaire and the 2010 Fibromyalgia Severity Scale.

ESR and CRP Blood will be collected on the day of vaccination and 6 weeks later.

The immunogenicity of the vaccine will be tested by Haemagglutination inhibition (HI) test.

Influenza virus has two important surface glycoproteins: the haemagglutinin (HA) and the neuraminidase (NA). Antigenic classification and subtyping of influenza viruses is based on these two glycoproteins. HA plays a key role in virus cell entry by binding to cell surface receptors, which are found also on red blood cells of certain species. Binding to red cells results in haemagglutination, which can be observed as a carpet of agglutinated red cells at the bottom of a tube or microtitre well. In the HI test, antibody directed against the viral haemagglutinins block the virus from binding to the blood cells and thus inhibits the haemagglutination reaction.

The pre- and post immunization HI antibodies were tested at the Central Virology Laboratory of the Israeli Ministry of Health using the HI test according to a standard WHO procedure 16. Sera will be separated, code labeled, and stored at -20°C until tested. Sera will be treated with receptor destroying enzyme cholera filtrate to remove non-specific inhibitors, and with Turkey red blood cells to remove non-specific agglutinins. The treated sera will be tested by HI test against the three antigens included in the vaccine: A/California (CAL), A/Wisconsin and B/Malaysia. The working dilution (test dose) of each antigen contained four haemagglutinin units in 25 µl of antigen. Test doses will be diluted in phosphate buffered saline (PBS) and added to serial dilution of antiserum. The haemagglutinin inhibition titer will be determined as the highest dilution of serum that completely inhibits haemagglutination of red blood cells.

The titer of an antiserum not showing any inhibition will be recorded as <10. Humoral response will be defined as either a fourfold or more rise in titer, or a rise from a non-protective baseline level of <1/40 to 1/40 in HI antibodies four weeks after vaccination 17,18. Geometric mean titers of antibody will be calculated to assess the immunity of the whole group.