Safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: a Phase I dose escalating study in healthy volunteers.
Live attenuated influenza vaccine (LAIV) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. LAIVs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of seasonal influenza strains. Two types of MDV lineages have been described, the Ann Arbor lineages and the A/Leningrad/17 and B/USSR/60 lineages. Here the safety and immunogenicity of a Madin Darby Canine Kidney - cell culture based, intranasal LAIV derived from A/Leningrad/17 and B/USSR, was evaluated in healthy influenza non-naive volunteers 18-50 years of age. In a double-blind, randomized, placebo-controlled design, single escalating doses of 1×10(5), 1×10(6), or 1×10(7) tissue culture infectious dose 50% (TCID50) of vaccine containing each of the three influenza virus re-assortants recommended by the World Health Organization for the 2008-2009 season were administered intranasally. A statistically significant geometric mean increase in hemagglutination inhibition titer was reached for influenza strain A/H3N2 after immunization with all doses of LAIV. For the A/H1N1 and B strains, the GMI in HI titer did not increase for any of the doses. Virus neutralization antibody titers showed a similar response pattern. A dose-response effect could not be demonstrated for any of the strains, neither for the HI antibody nor for the VN antibody responses. No influenza like symptoms, no nasal congestions, no rhinorrhea, or other influenza related upper respiratory tract symptoms were observed. In addition, no difference in the incidence or nature of adverse events was found between vaccine and placebo treated subjects. Overall, the results indicated that the LAIV for nasal administration is immunogenic (i.e. able to provoke an immune response) and safe both from the perspective of the attenuated virus and the MDCK cell line from which it was derived, and it warrants further development.
['Heldens|Jacco|J|', 'Hulskotte|Ellen|E|', 'Voeten|Theo|T|', 'Breedveld|Belinda|B|', 'Verweij|Pierre|P|', 'van Duijnhoven|Wilbert|W|', 'Rudenko|Larissa|L|', 'van Damme|Pierre|P|', 'van den Bosch|Han|H|']
D000293:Adolescent D000328:Adult D000818:Animals D057134:Antibodies, Neutralizing D000914:Antibodies, Viral D004285:Dogs D004311:Double-Blind Method D005260:Female D006385:Hemagglutination Inhibition Tests D006801:Humans D053118:Influenza A Virus, H1N1 Subtype D053122:Influenza A Virus, H3N2 Subtype D009981:Influenza B virus D007252:Influenza Vaccines D007251:Influenza, Human D061985:Madin Darby Canine Kidney Cells D008297:Male D008875:Middle Aged D014613:Vaccines, Attenuated D055815:Young Adult
Cell culture Live attenuated Influenza Vaccine Phase I Healthy volunteers Clinical trial