title: Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine.
abstract: Vaccines used against seasonal influenza are poorly effective against influenza A viruses of novel subtypes that may have pandemic potential. Furthermore, pre(pandemic) influenza vaccines are poorly immunogenic, which can be overcome by the use of adjuvants. A limited number of adjuvants has been approved for use in humans, however there is a need for alternative safe and effective adjuvants that can enhance the immunogenicity of influenza vaccines and that promote the induction of broad-protective T cell responses. Here we evaluated a novel nanoparticle, G3, as an adjuvant for a seasonal trivalent inactivated influenza vaccine in a mouse model. The G3 adjuvant was formulated with or without steviol glycosides (DT, for diterpenoid). The use of both formulations enhanced the virus-specific antibody response to all three vaccine strains considerably. The adjuvants were well tolerated without any signs of discomfort. To assess the protective potential of the vaccine-induced immune responses, an antigenically distinct influenza virus strain, A/Puerto Rico/8/34 (A/PR/8/34), was used for challenge infection. The vaccine-induced antibodies did not cross-react with strain A/PR/8/34 in HI and VN assays. However, mice immunized with the G3/DT-adjuvanted vaccine were partially protected against A/PR/8/34 infection, which correlated with the induction of anamnestic virus-specific CD8(+) T cell responses that were not observed with the use of G3 without DT. Both formulations induced maturation of human dendritic cells and promoted antigen presentation to a similar extent. In conclusion, G3/DT is a promising adjuvant formulation that not only potentiates the antibody response induced by influenza vaccines, but also induces T cell immunity which could afford broader protection against antigenically distinct influenza viruses.
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Carolien E
authors.initials: CE
authors.lastname: van de Sandt
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Joost H C M
authors.initials: JH
authors.lastname: Kreijtz
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Martina M
authors.initials: MM
authors.lastname: Geelhoed-Mieras
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Stella E
authors.initials: SE
authors.lastname: Vogelzang-van Trierum
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Nella J
authors.initials: NJ
authors.lastname: Nieuwkoop
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: David A M C
authors.initials: DA
authors.lastname: van de Vijver
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands; ViroClinics Biosciences BV, Marconistraat 16, 3029 AK Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Infectious Diseases Department of Medical Sciences, Uppsala University, MoreinX, Dag Hammarskjöldsväg 34 A, 751 83 Uppsala, Sweden.
authors.forename: Bror
authors.initials: B
authors.lastname: Morein
authors.affiliation: Department of Viroscience, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands; ViroClinics Biosciences BV, Marconistraat 16, 3029 AK Rotterdam, The Netherlands. Electronic address: g.rimmelzwaan@erasmusmc.nl.
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D009981:Influenza B virus; D007252:Influenza Vaccines / Q000276:immunology*; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004224:Diterpenes; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Adjuvant; Heterosubtypic immunity; Split virion vaccine; T cells