A Liposome-Based Adjuvant Containing Two Delivery Systems with the Ability to Induce Mucosal Immunoglobulin A Following a Parenteral Immunization

Christensen, Dennis; Hansen, Lasse Bøllehuus; Leboux, Romain; Jiskoot, Wim; Christensen, Jan Pravsgaard; Andersen, Peter; Dietrich, Jes

doi:10.1021/acsnano.8b05209

Cited by 25 publications

(28 citation statements)

References 54 publications

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“…To conclude, potent mucosal CD8 + T cell and humoral responses have been achieved using systemic immunization (114–116), which indicates the feasibility of improving parenteral injection-based vaccine strategies. However, the mechanisms involved have not been elucidated.…”

Section: Discussionmentioning

confidence: 94%

Site-Specific DC Surface Signatures Influence CD4+ T Cell Co-stimulation and Lung-Homing

et al. 2019

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Dendritic cells (DCs) that drain the gut and skin are known to favor the establishment of T cell populations that home to the original site of DC-antigen (Ag) encounter by providing soluble “imprinting” signals to T cells in the lymph node (LN). To study the induction of lung T cell-trafficking, we used a protein-adjuvant murine intranasal and intramuscular immunization model to compare in vivo -activated Ag + DCs in the lung and muscle-draining LNs. Higher frequencies of Ag + CD11b + DCs were observed in lung-draining mediastinal LNs (MedLN) compared to muscle-draining inguinal LNs (ILN). Ag + CD11b + MedLN DCs were qualitatively superior at priming CD4 + T cells, which then expressed CD49a and CXCR3, and preferentially trafficked into the lung parenchyma. CD11b + DCs from the MedLN expressed higher levels of surface podoplanin, Trem4, GL7, and the known co-stimulatory molecules CD80, CD86, and CD24. Blockade of specific MedLN DC molecules or the use of sorted DC and T cell co-cultures demonstrated that DC surface phenotype influences the ability to prime T cells that then home to the lung. Thus, the density of dLN Ag + DCs, and DC surface molecule signatures are factors that can influence the output and differentiation of lung-homing CD4 + T cells.

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Section: Discussionmentioning

confidence: 94%

Site-Specific DC Surface Signatures Influence CD4+ T Cell Co-stimulation and Lung-Homing

et al. 2019

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“…A combination of fast and prolonged releasing liposomes was used by Christensen et al as a parenteral vaccine strategy able to generate a long-lasting intestinal immune response to prevent enteric infections [61]. The fast releasing system comprised retinoic acid in PEGylated liposomes to pre-condition the vaccine-draining lymph nodes.…”

Section: Liposomal Systemsmentioning

confidence: 99%

Injectable Lipid-Based Depot Formulations: Where Do We Stand?

Rahnfeld

Luciani

2020

Pharmaceutics

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The remarkable number of new molecular entities approved per year as parenteral drugs, such as biologics and complex active pharmaceutical ingredients, calls for innovative and tunable drug delivery systems. Besides making these classes of drugs available in the body, injectable depot formulations offer the unique advantage in the parenteral world of reducing the number of required injections, thus increasing effectiveness as well as patient compliance. To date, a plethora of excipients has been proposed to formulate depot systems, and among those, lipids stand out due to their unique biocompatibility properties and safety profile. Looking at the several long-acting drug delivery systems based on lipids designed so far, a legitimate question may arise: How far away are we from an ideal depot formulation? Here, we review sustained release lipid-based platforms developed in the last 5 years, namely oil-based solutions, liposomal systems, in situ forming systems, solid particles, and implants, and we critically discuss the requirements for an ideal depot formulation with respect to the used excipients, biocompatibility, and the challenges presented by the manufacturing process. Finally, we delve into lights and shadows originating from the current setups of in vitro release assays developed with the aim of assessing the translational potential of depot injectables.

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“…More recently, a vaccine using two liposomal delivery systems that were subcutaneously administered to mice induced antigen-specific intestinal IgA responses. The first delivery system was designed to ensure fast drainage of ATRA towards the lymph nodes to precondition these for mucosal immune responses, while the second delivery system was optimized for slower, prolonged delivery of the antigen to these ATRA preconditioned lymph nodes via migrating antigen-presenting cells [149]. In the future, it would be interesting to see if similar results could be obtained in large animal models.…”

Section: Use Of Adjuvants For the Induction Of Siga After Parenteral mentioning

confidence: 99%

Advances in Oral Subunit Vaccine Design

2020

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Many pathogens invade the host at the intestinal surface. To protect against these enteropathogens, the induction of intestinal secretory IgA (SIgA) responses is paramount. While systemic vaccination provides strong systemic immune responses, oral vaccination is the most efficient way to trigger protective SIgA responses. However, the development of oral vaccines, especially oral subunit vaccines, is challenging due to mechanisms inherent to the gut. Oral vaccines need to survive the harsh environment in the gastrointestinal tract, characterized by low pH and intestinal proteases and need to reach the gut-associated lymphoid tissues, which are protected by chemical and physical barriers that prevent efficient uptake. Furthermore, they need to surmount default tolerogenic responses present in the gut, resulting in suppression of immunity or tolerance. Several strategies have been developed to tackle these hurdles, such as delivery systems that protect vaccine antigens from degradation, strong mucosal adjuvants that induce robust immune responses and targeting approaches that aim to selectively deliver vaccine antigens towards specific immune cell populations. In this review, we discuss recent advances in oral vaccine design to enable the induction of robust gut immunity and highlight that the development of next generation oral subunit vaccines will require approaches that combines these solutions.

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A Liposome-Based Adjuvant Containing Two Delivery Systems with the Ability to Induce Mucosal Immunoglobulin A Following a Parenteral Immunization

Cited by 25 publications

References 54 publications

Site-Specific DC Surface Signatures Influence CD4+ T Cell Co-stimulation and Lung-Homing

Site-Specific DC Surface Signatures Influence CD4+ T Cell Co-stimulation and Lung-Homing

Injectable Lipid-Based Depot Formulations: Where Do We Stand?

Advances in Oral Subunit Vaccine Design

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