Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine

被引:11
作者
de Sandt, Carolien E. van [1 ]
Kreijtz, Joost H. C. M. [1 ]
Geelhoed-Mieras, Martina M. [1 ]
Vogelzang-van Trierum, Stella E. [1 ]
Nieuwkoop, Nella J. [1 ]
van de Vijver, David A. M. C. [1 ]
Fouchier, Ron A. M. [1 ]
Osterhaus, Albert D. M. E. [1 ,2 ]
Morein, Bror [3 ]
Rimmelzwaan, Guus F. [1 ,2 ]
机构
[1] Erasmus MC, Dept Virosci, NL-3000 CA Rotterdam, Netherlands
[2] ViroClin Biosci BV, NL-3029 AK Rotterdam, Netherlands
[3] Uppsala Univ, Infect Dis Dept Med Sci, MoreinX, S-75183 Uppsala, Sweden
关键词
Adjuvant; Split virion vaccine; T cells; Heterosubtypic immunity; A VIRUS-INFECTION; IMMUNE-STIMULATING COMPLEXES; SWINE-ORIGIN; 2009; HETEROSUBTYPIC IMMUNITY; PANDEMIC INFLUENZA; LETHAL INFECTION; A/H5N1; VIRUS; CROSS-REACT; IMMUNOSTIMULATING COMPLEXES; AIRBORNE TRANSMISSION;
D O I
10.1016/j.vaccine.2014.08.003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5614 / 5623
页数:10
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