New Technology in Influenza Vaccination
Advances in Influenza Vaccination
New Technology in Influenza Vaccination
Speaker: David P. Greenberg, MD, Senior Director, Scientific and Medical Affairs, US, Sanofi Pasteur; Adjunct Associate Professor of Pediatrics, University of Pittsburgh School of Medicine; Pediatric Infectious Diseases, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA.
Dr. David Greenberg’s discussion focused on novel technologies that could improve the immunogenicity achieved with influenza vaccines as well as increase vaccination rates among both older and younger adults.
Dr. Greenberg initially focused on results of studies with a high-dose intramuscular vaccine tested on older adults. Older adults’ declining humoral and cellular immunity, due to immunosenescence, increases their susceptibility to infection and decreases their immunologic responses to vaccines. As a result, older adults’ response to vaccination may be poor, yielding fewer protective antibodies. Higher-dose vaccines are being pursued to overcome this limitation.
Dr. Greenberg detailed a Phase 3 clinical trial of a high-dose influenza vaccine (60µg hemagglutinin [HA]/strain [H1N1, H3N2, and B]) that found value to the approach.1 This randomized multicentre trial of 3,876 individuals, all ≥65 years of age and medically stable, compared high-dose vaccine versus standard-dose vaccine (Fluzone®, sanofi pasteur; 15µg HA/strain). The high-dose trivalent, inactivated influenza vaccine offered a fourfold higher antigen content compared with standard dose vaccine. Researchers reported significantly higher seroconversion and seroprotection rates and significantly higher hemagglutination inhibition (HAI) geometric mean antibody titres (GMTs) 28 days after vaccination among subjects who received high-dose vaccine compared with those who received standard-dose vaccine. Using strict U.S. Food and Drug Administration criteria, the high-dose vaccine demonstrated statistically superior immunogenicity compared with standard-dose vaccine (immunologic superiority for both A strains [H1N1 and H3N2] and noninferiority for the B strain). Local injection site reactions occurred more frequently in individuals who received the high-dose vaccine, but the reactions were generally mild to moderate.
Influenza-associated morbidity and mortality remains substantial among older adults, Dr. Greenberg emphasized, and the improved immunogenicity response elicited by the high-dose vaccine is likely to provide improved protective benefits for this population.
The next development in immunization research Dr. Greenberg discussed concerned seasonal influenza vaccination by intradermal microinjection (Figure 1). This is another approach to address the reduced immunogenicity of influenza vaccines among older adults that results from immunosenescence. Additionally, in healthy younger adults, vaccine uptake remains low. An intradermal delivery system offers an alternative that may improve vaccination rates and extend protection to people who might not otherwise receive annual influenza vaccination.
The physiologic principle of intradermal vaccination takes advantage of dendritic cells, which are the antigen presenting cells in the dermal layer. The dermal layer is also rich in lymphatic and blood supply, making it a robust arm of the immune system.
Dr. Greenberg reviewed results of two relevant Phase 2 clinical studies of intradermal vaccines.
The first was a multicentre, randomized study of 1,107 volunteers ≥60 years of age.2 Participants received intradermal trivalent inactivated influenza vaccine containing 15 or 21mg of HA per strain or intramuscular control vaccine (Vaxigrip®, sanofi pasteur, 15 mg HA/strain). The primary endpoints of the study were the strain-specific HAI GMTs 21 days after vaccination. The authors of the study reported that, for each strain, the GMTs noted in association with each intradermal vaccine were superior to those noted with the intramuscular control.
The second was a Phase 2, multicentre, randomized open-label study of 978 healthy adults under age 60, which evaluated the immunogenicity and safety