A liposomal vaccine promotes strong adaptive immune responses via dendritic cell activation in draining lymph nodes

Maria Agallou; Maritsa Margaroni; Evgenia Tsanaktsidou; Fotis Badounas; Olga Kammona; Costas Kiparissides; Evdokia Karagouni

doi:10.1016/j.jconrel.2023.03.006

A liposomal vaccine promotes strong adaptive immune responses via dendritic cell activation in draining lymph nodes

J Control Release. 2023 Apr:356:386-401. doi: 10.1016/j.jconrel.2023.03.006. Epub 2023 Mar 11.

Authors

Maria Agallou¹, Maritsa Margaroni¹, Evgenia Tsanaktsidou², Fotis Badounas³, Olga Kammona², Costas Kiparissides⁴, Evdokia Karagouni⁵

Affiliations

¹ Immunology of Infection Laboratory, Hellenic Pasteur Institute, Athens 125 21, Greece.
² Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, P.O. Box 60361, Thessaloniki 57 001, Greece.
³ Molecular Genetics Laboratory, Department of Immunology, Transgenic Technology Laboratory, Hellenic Pasteur Institute, Athens 125 21, Greece.
⁴ Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, P.O. Box 60361, Thessaloniki 57 001, Greece; Department of Chemical Engineering, Aristotle University of Thessaloniki, P.O. Box 472, Thessaloniki 54 124, Greece.
⁵ Immunology of Infection Laboratory, Hellenic Pasteur Institute, Athens 125 21, Greece. Electronic address: ekaragouni@pasteur.gr.

PMID: 36893900
DOI: 10.1016/j.jconrel.2023.03.006

Abstract

Subunit proteins provide a safe source of antigens for vaccine development especially for intracellular infections which require the induction of strong cellular immune responses. However, those antigens are often limited by their low immunogenicity. In order to achieve effective immune responses, they should be encapsulated into a stable antigen delivery system combined with an appropriate adjuvant. As such cationic liposomes provide an efficient platform for antigen delivery. In the present study, we describe a liposomal vaccine platform for co-delivery of antigens and adjuvants able to elicit strong antigen-specific adaptive immune responses. Liposomes are composed of the cationic lipid dimethyl dioctadecylammonium bromide (DDAB), cholesterol (CHOL) and oleic acid (OA). Physicochemical characterization of the formulations showed that their size was in the range of ∼250 nm with a positive zeta potential which was affected in some cases by the enviromental pH facilitating endosomal escape of potential vaccine cargo. In vitro, liposomes were effectively taken up by bone marrow dendritic cells (BMDCs) and when encapsulated IMQ they promoted BMDCs maturation and activation. Upon in vivo intramuscular administration, liposomes' active drainage to lymph nodes was mediated by DCs, B cells and macrophages. Thus, mice immunization with liposomes having encapsulated LiChimera, a previously characterized anti-leishmanial antigen, and IMQ elicited infiltration of CD11b^low DCs populations in draining LNs followed by increased antigen-specific IgG, IgG2a and IgG1 levels production as well as indcution of antigen-specific CD4⁺ and CD8⁺ T cells. Collectively, the present work provides a proof-of-concept that cationic liposomes composed of DDAB, CHOL and OA adjuvanted with IMQ provide an efficient delivery platform for protein antigens able to induce strong adaptive immune responses via DCs targeting and induction of maturation.

Keywords: Adjuvant; Dendritic cells; Imiquimod; Innate response; Liposome; Subunit chimeric vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Animals
Antigens
CD8-Positive T-Lymphocytes*
Dendritic Cells
Immunity, Humoral
Liposomes / chemistry
Lymph Nodes / metabolism
Mice
Mice, Inbred C57BL
Vaccines* / pharmacology

Substances

didodecyldimethylammonium
Liposomes
Adjuvants, Immunologic
Vaccines
Antigens