Yearly licensing studies from 1997 to 2007 of the inactivated whole virus seasonal influenza vaccine fluval – a useful approach to pandemic vaccine development even in less well developed countries?

Abstract

Objective Seasonal vaccination has been consistently shown to significantly reduce morbidity and mortality because of influenza epidemics, even in healthy, working adults. Here we report the results of the yearly licensing studies of the past 11 influenza seasons (1997–2007) with a trivalent, inactivated whole virus vaccine with an aluminum phosphate adjuvant system. Methods Sixty healthy volunteers per age group (18–60 years and 60 years and older) were enrolled to receive vaccination each year, thus, a total of 1080 subjects were studied. Serum antibody titers were measured by hemagglutination inhibition (HI). Results: The vaccine met the criteria for licensing each year, meaning seroprotection (achievement of an HI titer of >1:40 in >70% of subjects); seroconversion, i.e. a >4‐fold increase in HI antibody titer, or reaching a titer of >1:40, in >40% of subjects; and an increase in geometric mean titers by >2·5‐fold. Side effects were rare and mild. The same method was used to produce a pre‐pandemic vaccine against influenza A (H5N1), which has been shown to be safe and immunogenic in humans. Conclusions We conclude that the method presented is safe, effective and may serve as a useful approach to seasonal and pandemic vaccine production even in less well‐developed countries by means of technological transfer.

A Single-Dose Influenza A (H5N1) Vaccine Safe and Immunogenic in Adult and Elderly Patients: an Approach to Pandemic Vaccine Development

“…There was no significant difference in the occurrence of adverse events between any of the groups. Notably, these results agree with a previous clinical trial of the present vaccine and with the 13-year experience of more than 16 million vaccinations in humans, using the seasonal influenza vaccine produced by the same method (24,25).…”

“…Briefly, with the exception of the virus strain, the vaccine was made by the same method as that used for the seasonal influenza vaccine, FluvalAB, for the past 13 years (15,20). The seasonal vaccine produced by this method has met the requirements of the European Agency for the Evaluation of Medicinal Products (EMEA) for interpandemic influenza vaccines each year since 1995 and has been administered safely to humans in a total of over 16 million cases (5,25).…”

A Reduced-Dose Seasonal Trivalent Influenza Vaccine Is Safe and Immunogenic in Adult and Elderly Patients in a Randomized Controlled Trial

“…4807) was also produced by Omninvest, as described in detail elsewhere (19). Like most licensed trivalent inactivated seasonal influenza vaccines, it contained 15 g of HA/strain/dose.…”

“…The reduced-dose vaccine (Fluval K, an inactivated, wholevirion, trivalent vaccine with 6 g of HA/strain/0.5 ml content and aluminum phosphate gel adjuvant; lot no. FL-K-004) was produced by Omninvest Ltd. (Budapest, Hungary) as described previously (8,(14)(15)(16)(17)(18)(19). With the exception of the antigen amount, the vaccine was prepared by the same method as for the licensed seasonal influenza vaccine Fluval AB (19) and the licensed prepandemic vaccine Fluval H5N1 and the licensed pandemic H1N1 vaccine Fluval P (8,(14)(15)(16)(17)(18).…”

Az új, csökkentett dózisú, hazai gyártású influenzavakcina (FluArt) forgalomba hozatalát követő első szezonjának biztonságossági vizsgálata

“…A használt technológia mellett a hatóanyag-tartalom növelése az immunválaszban további növekedést nem okozott [7]. A fejlesztést alátámasztotta az általunk korábban, szintén 6 µg hatóanyag-tartalmú pandémiás (H1N1) influenzavakcinákkal folytatott klinikai vizsgálatok eredménye, valamint a 2009. évi pandémia idején alkalmazott oltó-anyag vírusfertőzéssel szembeni hatékonysága [5][6][7][12][13][14][15]. A klinikai vizsgálati készítmények eredményei alapján az új, 6 µg hatóanyag-tartalmú készítmény forgalomba hozatali engedély megszerzését követően (OGYI-T-8998/03) a 2015/2016-os szezonban került először a piacra, 3FluArt néven.…”