Italian post marketing surveillance for adverse event reports after MF59-adjuvanted H1N1 vaccination

Regional Center for Pharmacovigilance and Pharmacoepidemiology, Department of Experimental Medicine, Section of Pharmacology L. Donatelli, Faculty of Medicine and Surgery, Second University of Naples, Via De Crecchio, 7, 80138 Naples, Italy.
Vaccine (Impact Factor: 3.62). 03/2011; 29(20):3708-13. DOI: 10.1016/j.vaccine.2011.02.097
Source: PubMed


According to European recommendations, the Italian Medicines Agency (AIFA) required close monitoring of the safety of the MF59-adjuvanted H1N1v vaccine, which was the only vaccine available in Italy for prophylaxis of the A/H1N1 (2009) pandemic influenza. From October 2009 to June 2010, the Italian Pharmacovigilance Adverse Event (AE) Spontaneous Reporting System [Rete Nazionale Farmacovigilanza] (RNF) received 1330 reports of AEs temporally related with the pandemic influenza vaccination out of a total of 924,057 doses administered. Among these, 1,162 (87.37%) AE reports were classified 'non serious', 91 (6.84%) 'serious', 3 (0.23%) had a fatal outcome and 74 (5.56%) did not include the degree of seriousness. Among the serious AE reports, some unexpected AEs emerged. Even though some typical vaccine safety issues which emerged should be further explored, such as vaccination in pregnancy, the analysis of all AE reports sent to RNF shows that the vaccine has a well-tolerated safety profile which resembles that of the already available seasonal influenza vaccines. This contrasts with the widespread public concern about its safety, which has been one of the major causes of the low vaccination rate observed in Italy, as well as in other countries.

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    • "In this context, AIFA has promoted several projects and studies in Italy, with the aim of increasing knowledge on drugs and the “Culture of Pharmacovigilance”, through the establishment of Pharmacovigilance Regional Centers.[44] These centers have a key role in the most advanced national pharmacovigilance systems. "
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    ABSTRACT: Spontaneous reporting of adverse drug reactions (ADRs) is the basis of pharmacovigilance. In fact, ADRs are associated with a high degree of morbidity and mortality. However, underreporting by all healthcare professionals remains the major problem in Italy and in the rest of the world. The dissemination of pharmacovigilance knowledge among Italian healthcare professionals, and the new pharmacovigilance regulations may promote the early detection and reporting of ADRs. This review examines the legislative framework concerning the pharmacovigilance in Italy. The information was collected from scientific articles and the websites of the Italian Ministry of Health and the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The pharmacovigilance system, both in Italy and Europe, has undergone profound changes. European legislation on pharmacovigilance has been changed in 2010 according to the EU Regulation 1235/2010 and Directive 2010/84/EU. Basically, the changes tend to increase the efficiency, speed and transparency of pharmacovigilance activities. The new Regulation (1235/2010) and the Directive (2010/84/EU) aim to strengthen the system of pharmacovigilance, establish more precisely who is obliged to do what, and allow faster and easier circulation and retrieval of information about ADRs. A greater knowledge on what is the Italian pharmacovigilance legislation will be useful to improve the status of ADRs reporting and spread the culture of spontaneous reporting.
    Full-text · Article · Dec 2013 · Journal of Pharmacology and Pharmacotherapeutics
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    • "MF59 is an oil-in-water emulsion adjuvant, which has been formulated in vaccines licensed for human use [12]. Although adverse effects of MF59 are rare, the events such fever, chills, malaise, myalgia, arthralgia, nausea, headache and rash have been found after immunization of MF59-adjuvanted vaccines [13,14]. Therefore, searching for new vaccine adjuvants remain an interesting topic. "
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    ABSTRACT: Vaccination remains one of the most effective approaches to prevent the spread of infectious diseases. Immune responses to vaccination can be enhanced by inclusion of adjuvant in a vaccine. Paclitaxel extracted from the bark of the Pacific yew tree Taxus brevifola was previously demonstrated to have adjuvant property. Compared to paclitaxel, docetaxel is another member of taxane family, and is more soluble in water and easier to manipulate in medication. To investigate the adjuvant effect of this compound, we measured the immune responses induced by co-administration of a split inactivated influenza H1N1 vaccine antigen with docetaxel. When co-administered with docetaxel, lower dose antigen (equivalent to 10 ng HA) induced similar levels of IgG and IgG isotypes as well as HI titers to those induced by higher dose antigen (equivalent to 100 ng HA). Docetaxel promoted splenocyte responses to H1N1 antigen, ConA and LPS, mRNA expressions of cytokines (IFN-gamma, IL-12, IL-4 and IL-10) and T-bet/GATA-3 by splenocytes. The enhanced immunity was associated with up-expressed microRNAs (miR-155, miR-150 and miR-146a) in docetaxel-stimulated RAW264.7 cells. Docetaxel promoted similar IgE level to but alum promoted significantly higher IgE level than the control. Docetaxel has adjuvant effect on the influenza H1N1 vaccine by up-regulation of Th1/Th2 immune responses. Considering its unique vaccine adjuvant property as well as the safe record as an anti-neoplastic agent clinically used in humans during a long period, docetaxel should be further studied for its use in influenza vaccine production.
    Full-text · Article · Jul 2012 · BMC Immunology
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    ABSTRACT: MF59-adjuvanted seasonal trivalent inactivated (ATIV) vaccine licensed since 1997 and MF59-adjuvanted pandemic H1N1 vaccines have been distributed to approximately 80M persons. Addition of the emulsion adjuvant to inactivated vaccine formulations provides for higher levels of antibody to the viral hemagglutinin (HA) in less responsive older adults, infants and children which, in the case of the pandemic vaccine, allowed only 3.75 µg of the HA to be immunogenic. The adjuvant also stimulates production of more broadly-reactive antibodies against strains that are mismatched to those in the vaccine, a potential advantage in the face of perennial influenza virus antigenic drift. In a field trial, ATIV was 89% efficacious in preventing laboratory-confirmed influenza in 6-<72 month old children, 81% more efficacious than the unadjuvanted control split vaccine while, in older adults, ATIV reduced community-acquired pneumonia and influenza hospitalizations in adults >65 years old by 23% compared to unadjuvanted vaccine, in an observational study. The effectiveness of MF59 adjuvanted split pandemic H1N1 vaccine was 74% overall. Unadjuvanted pandemic vaccine was poorly immunogenic in HIV-infected persons, whereas their responses to MF59-adjuvanted vaccine were similar to those of healthy controls. Analyses of the clinical trials and pharmacovigilance databases and observational studies have shown that while MF59-adjuvanted influenza vaccines are more locally reactogenic, they have not been associated with an increased risk for various adverse effects (AE) of special interest, including unsolicited neurological or autoimmune events.
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