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Vaccines 2017, 5(3), 19; doi:10.3390/vaccines5030019

Adjuvantation of Pulmonary-Administered Influenza Vaccine with GPI-0100 Primarily Stimulates Antibody Production and Memory B Cell Proliferation

1
Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
2
Department of Communicable Diseases, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune-Satara Road, Katraj-Dhankawadi, Pune 411043, Maharashtra, India
3
Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands
Current address: Department of Medical Microbiology, University Medical Center Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands.
*
Author to whom correspondence should be addressed.
Academic Editor: Florian Krammer
Received: 12 April 2017 / Revised: 19 June 2017 / Accepted: 21 July 2017 / Published: 27 July 2017
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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. View Full-Text
Keywords: influenza; pulmonary immunization; adjuvant; immune mechanisms influenza; pulmonary immunization; adjuvant; immune mechanisms
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MDPI and ACS Style

Patil, H.P.; Herrera Rodriguez, J.; de Vries-Idema, J.; Meijerhof, T.; Frijlink, H.W.; Hinrichs, W.L.J.; Huckriede, A. Adjuvantation of Pulmonary-Administered Influenza Vaccine with GPI-0100 Primarily Stimulates Antibody Production and Memory B Cell Proliferation. Vaccines 2017, 5, 19.

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