Authors:	Roßmann, Laura
Title:	In-depth immunological analysis of prototypic adjuvants for vaccine formulations
Online publication date:	10-Dec-2020
Year of first publication:	2020
Language:	english
Abstract:	Vaccine adjuvants have the potential to initiate, amplify and shape the immune response against the vaccine antigen depending on their inherent mode of action (MoA). Thus, the appropriate selection of the adjuvant is of pivotal importance for vaccine efficacy. In order to control newly emerging or existing pathogens such as SARS-CoV-2, HIV or M. tuberculosis, effective adjuvants eliciting a specific immune response will have a critical role within next generation vaccine formulations. However, even for the best-known adjuvants, such as aluminium hydroxide (Al(OH)3), some aspects of their modes of action (MoAs) still remain elusive, making the corresponding immune response difficult to predict. In this study, we systematically assessed the adjuvants’ immunomodulatory MoAs on human monocyte-derived dendritic cells (DCs) and their effect on the arising adaptive immune response. To this end, we compared ten structurally and functionally different single component adjuvants in an in vitro human primary immune cell-based assay composed of DCs co-cultured with autologous peripheral blood lymphocytes (PBLs). By investigating maturation markers and endocytosis capacity by flow cytometry, we observed that the adjuvants TDB, Al(OH)3, AddaVaxTM and Quil-A exert only weak effects on DCs, whereas the other adjuvants tested induce a strong DC maturation. We further analyzed 25 secreted cytokines and chemokines from the DC:PBL culture supernatant using a Luminex multiplex assay and revealed adjuvant-specific protein patterns even for adjuvants targeting the same receptor. To assess the effect on the adaptive immune response, we examined the ability of the adjuvants to induce antigen-independent proliferation of PBLs co-cultured with the DCs. We found that Pam3CSK4, Gardiquimod, Resiquimod, and two variants of monophosphoryl lipid A (MPL-s and MPL-SM) induced antigen-independent proliferation of PBLs to varying degrees, with Resiquimod being the strongest stimulator. A detailed examination of B-, NK-, NKT-, CD4+ and CD8+ T cells within the proliferated PBL population demonstrated that each adjuvant promoted the proliferation of different lymphocyte subsets. When testing the adjuvants’ immunostimulating potential in an antigen-specific context, we found that Pam3CSK4, MPL-s and Al(OH)3 increased the proportion of FluM1-specific CD8+ T cells significantly. These adjuvant-expanded T cells were still polyfunctional as determined by their secretion of pro-inflammatory cytokines as well as their degranulation upon re-stimulation with the FluM1 peptide. Taken together, our results provide a comprehensive overview of the immunogenic effects of prototypic candidate or established adjuvants on primary human immune cells. The detailed data obtained on their distinct immune signatures will contribute to facilitate the selection of suitable adjuvants for the development of tailored vaccines.
DDC:	570 Biowissenschaften 570 Life sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 10 Biologie Externe Einrichtungen
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5396
URN:	urn:nbn:de:hebis:77-openscience-856bf26f-7681-4155-8464-77999d227a057
Version:	Original work
Publication type:	Dissertation
License:	In Copyright
Information on rights of use:	https://rightsstatements.org/page/InC/1.0/?language=en
Extent:	XVI, 164 Seiten
Appears in collections:	JGU-Publikationen