Lymphoid follicle antigen (Ag) delivery and enhanced rodent humoral immune responses mediated by Ag-containing PEGylated liposomes

• Published in: Vaccine 2021-02, Vol.39 (7), p.1131-1139
• Main Authors: Shimizu, Taro, Watanabe, Yuki, Ando, Hidenori, Ishima, Yu, Ishida, Tatsuhiro
• Format: Article
• Language: English
• Subjects: Accumulation; Adaptive immunity; Adaptive systems; Animal models; Animals; Antigen presentation; Antigens; Cell-mediated immunity; Dendritic cells; Egress; Experiments; Follicles; FTY720; Humoral immune response; Humoral immunity; Immune response (humoral); Immunity; Immunity, Humoral; Immunization; Immunoglobulin G; Immunoglobulin G - immunology; Immunology; Injections; Intravenous administration; Laboratories; Liposomes; Lymphocytes; Lymphocytes T; Lymphoid follicle; Lymphoid tissue; Marginal zone B cell; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Ovalbumin; PEGylated liposome; Peptides; Polyethylene glycol; Polyethylene Glycols; Priming; Rats; Rodentia; Spleen; T-Lymphocytes - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2021.01.008

•Pretreatment with PEG-Lip triggered accumulation of second dose in splenic follicle.•PEG-Lip-mediated antigen delivery to splenic follicle elicited high IgG production.•Our intravenous immunization was superior to conventional subcutaneous immunization. Antigen (Ag) delivery to lymphoid follicles is important in achieving adaptive immunity. We recently developed a novel two-step Ag delivery system that efficiently induces cellular immune responses to Ags in mice by using priming intravenous (i.v.) injections of empty PEGylated liposomes (PEG-Lip) followed 3 days later by Ag-entrapped PEG-Lip (Ag-PEG-lip). In this study, we looked for humoral immune responses in rats and mice with IgG production specific to the encapsulated Ags. We observed that initial i.v. injections of empty PEG-Lip triggered accumulation of subsequent doses ovalbumin-PEG-Lip (OVA-PEG-lip) in splenic follicles and enhanced IgG production against OVA in both rats and mice. Anti-OVA IgG production was diminished by inhibition of splenic follicular accumulation of OVA-PEG-Lip by fingolimod (FTY720), which inhibits lymphocyte egress from lymphoid tissues. Thisindicates that the follicular accumulation of Ags that we observed is an indispensable and unique step in the production of anti-OVA IgG. Interestingly, in BALB/c nude mice, which are T cell deficient, a high follicular accumulation of OVA-PEG-Lip was observed, but anti-OVA IgG production was not observed. This suggests that T cells are also indispensable for the induction of cellular immune responses by our two-step immunization procedure. Our unique Ag delivery platform, which efficiently delivers Ags to splenic follicles, may be a useful technique for the enhancement of cellular immunity, as well as humoral immunity. Further experimental evaluation should be undertaken in relevant animal models in order for efficacy, safety and immunological correlates to be determined.