Abstract
Adjuvants are key components in vaccines, they help in reducing the required antigen dose but also modulate the phenotype of the induced immune response. We previously showed that GPI-0100, a saponin-derived adjuvant, enhances antigen-specific mucosal and systemic antibody responses to influenza subunit and whole inactivated influenza virus (WIV) vaccine administered via the pulmonary route. However, the impact of the GPI-0100 dose on immune stimulation and the immune mechanisms stimulated by GPI-0100 along with antigen are poorly understood. Therefore, in this study we immunized C57BL/6 mice via the pulmonary route with vaccine consisting of WIV combined with increasing amounts of GPI-0100, formulated as a dry powder. Adjuvantation of WIV enhanced influenza-specific mucosal and systemic immune responses, with intermediate doses of 5 and 7.5 μg GPI-0100 being most effective. The predominant antibody subtype induced by GPI-0100-adjuvanted vaccine was IgG1. Compared to non-adjuvanted vaccine, GPI-0100-adjuvanted WIV vaccine gave rise to higher numbers of antigen-specific IgA- but not IgG-producing B cells in the lungs along with better mucosal and systemic memory B cell responses. The GPI-0100 dose was negatively correlated with the number of influenza-specific IFNγ- and IL17-producing T cells and positively correlated with the number of IL4-producing T cells observed after immunization and challenge. Overall, our results show that adjuvantation of pulmonary-delivered WIV with GPI-0100 mostly affects B cell responses and effectively induces B cell memory.
Highlights
Adjuvants are important components of vaccines as they have the ability to enhance and to modify the immune responses induced against an antigen
We evaluated in more detail the immune mechanisms induced by pulmonary-delivered GPI-0100-adjuvanted influenza vaccine
Previous studies on pulmonary delivery of GPI-0100 along with influenza subunit or whole inactivated influenza virus (WIV) vaccine demonstrated that GPI-0100 is a potent adjuvant for induction of humoral responses [14]
Summary
Adjuvants are important components of vaccines as they have the ability to enhance and to modify the immune responses induced against an antigen. Many studies are ongoing to find effective mucosal adjuvants and to elucidate the mechanisms by which they can help to reduce the antigen content in a vaccine without compromising the immune response induced against the antigen itself. GPI-0100 has been shown to stimulate Th1 immunity, cytotoxic T lymphocytes (CTL) responses, and antibody production against co-delivered antigens [7]. Use of GPI-0100 as adjuvant for parenteral subunit or virosomal influenza vaccines allowed induction of robust and protective immune responses in mice even at very low antigen doses (8 ng) [1,2]
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