DK received honoraria and compensation of travel expenses from Novartis, Wyeth/Pfizer and GSK for presentations and advisory activities
DK received honoraria and compensation of travel expenses from Novartis, Wyeth/Pfizer and GSK for presentations and advisory activities. Funding This study was supported by funds provided by Novartis Vaccines. Supplemental Material Supplemental data for this article can be accessed around the publisher’s website. 987014_Supplementary_Material.docx:Click here to view.(13K, docx) Author Contributions MK, GL-R, HR, LR and DK participated in the conduct of the study, data acquisition and interpretation, and contributed to the development of the initial draft of the manuscript, reviewed and revised the manuscript, and approved the final manuscript as submitted. inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Security was monitored throughout the study. One vaccination with 3.75?g of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5?g of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer 1:40 in 70% of children in the 1C 3, 3C8, and 9C17 y cohorts; however, 2 vaccinations with nonadjuvanted 15?g A/H1N1 antigen were needed to achieve this response in the 1C 3 and 3C8 y cohorts. Among children aged 6C11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer 1:40 in 70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and security of the 3.75_halfMF59 (2 doses for children 12 months) and 7.5_fullMF59 vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3. 75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. strong class=”kwd-title” Keywords: adjuvant, cell-culture, H1N1, MF59, pandemic, pediatric Abbreviations AEadverse eventCHMPEuropean Committee for Medicinal Products for Human UseCIconfidence intervalGMRgeometric imply ratioGMTgeometric imply titerHIhemagglutination inhibitionMNmicroneutralizationPPSper-protocol setSAEserious adverse eventWHOWorld Health Business Introduction Young people from birth to 18 y of age were at significantly higher risk from the 2009 2009 A/H1N1 influenza pandemic than older adults,1-3 with the most severe infections in the beginning reported in children.4 Estimates suggest that the cumulative rate of developing clinical illness was increased by 30- to 80-fold among people aged 24?years compared with individuals aged 65?years.1 In addition to their heightened susceptibility to seasonal and pandemic influenza viruses, children are also important contributors to computer virus transmission.5,6 Mass immunization of children is considered essential to accomplish disease control that will decrease infection rates and the risk of viral transmission within families and communities.6-9 Health authorities and vaccine manufacturers have focused on the development of vaccines based on R112 the A/California/7/2009 viral strain, with numerous adjuvanted and nonadjuvanted formulations produced using both traditional and novel methods.10 One important enhance in the manufacture of influenza vaccines is the use of cell-culture to replace traditional egg-based production. This technology is not dependent on the availability of eggs, and facilitates enhanced developing control and potentially reduction in production lead occasions, all of which could R112 be pivotal in the event of another influenza pandemic. A number of controlled clinical trials confirm that oil-in-water adjuvants, such as MF59, meet the qualities required of a safe vaccine for diverse populations.11-19 In addition, MF59 has been shown to heighten antibody response to the A/H1N1 pandemic virus18,20C24 and has been endorsed by the World Health Business (WHO) for this indication.25 This study evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 vaccine in healthy children and adolescents. Results A total Rabbit Polyclonal to OR2B3 of 666 subjects were R112 enrolled (cohort 1; n = 159; cohort 2; n = 184; cohort 3; n = 172; cohort 4; n = 151). Data from one site (n = 86) were excluded from the analysis as a result of noncompliance with protocol requirements for a different clinical study. Subject disposition and demographics are shown in Figure 1 and Table 1, respectively. Table 1. Demographics and other baseline characteristics of subjects in cohorts 1, 2, 3 and 4 (enrolled population, excluding non-compliant site) thead th align=”left” rowspan=”1″ colspan=”1″ /th th align=”center” colspan=”3″ rowspan=”1″ Cohort 1 (9C17?years) /th th align=”center” colspan=”4″ rowspan=”1″ Cohort 2 (3C8?years) /th th align=”left” rowspan=”1″ colspan=”1″ /th th align=”center” rowspan=”1″ colspan=”1″ 3.75?g +halfMF59 (n = 80 ) /th th align=”center” rowspan=”1″ colspan=”1″ 7.5?g +fullMF59 (n = 79 ) /th th align=”center” rowspan=”1″ colspan=”1″ Total (n = 159 ) /th th align=”center” rowspan=”1″ colspan=”1″ 3.75?g +halfMF59 (n = 72 R112 ) /th th align=”center” rowspan=”1″ colspan=”1″ 7.5?g +fullMF59 (n = 73 ) /th th align=”center” rowspan=”1″ colspan=”1″ 15?g +noMF59 (n = 39 ) /th th align=”center” rowspan=”1″ colspan=”1″ Total (n = 184 ) /th /thead Age (years), mean SD13.22.713.22.713.22.75.51.95.31.75.21.55.31.7Age (months), mean SD166.932.7167.531.4167.232.071.624.769.621.668.420.170.122.5Sex, n (%)?Male39 (49)42 (53)81 (51)27 (38)42 (58)14 (36)83 (45)?Female41 (51)37 (47)78 R112 (49)45 (63)31 (42)25.