The kinetics of soluble and particulate antigen trafficking in the afferent lymph, and its modulation by aluminum-based adjuvant

Veer, Michael John de; Kemp, Joanna; Chatelier, Josh; Elhay, Martin J; Meeusen, Elza Nicole Theresia

doi:10.1016/j.vaccine.2010.07.056

Cited by 57 publications

(70 citation statements)

References 23 publications

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“…Consistent with this, injection of sterile liposomes alone or containing CpG induced neutrophils and monocytes to rapidly enter the afferent lymph within 4 h. Interestingly, the addition of CpG, a bacterial pathogenassociated molecular pattern, increased the total number of neutrophils leaving the injection site but did not significantly prolong the duration of a nonspecific neutrophil-associated inflammatory response at the site of injection. Consistent with previous studies using this model (26,28), the number and percentage of total DCs in afferent lymph is remarkably unaffected by vaccine adjuvants, including liposomes and CpG. This is in contrast to some murine studies, in which DCs accumulate within the lymph node following injection with CpG (34).…”

Section: Discussionsupporting

confidence: 88%

“…This is desirable when clearing a persistent infection; however, a mild inflammatory response with a strong immune outcome is preferable for human vaccination, in which excess inflammation can lead to enhanced reactogenicity (32). Our studies have shown that injection with most vaccine adjuvants and even sterile saline results in the rapid recruitment of neutrophils and monocytes within afferent lymph following injection (26,28,33). Consistent with this, injection of sterile liposomes alone or containing CpG induced neutrophils and monocytes to rapidly enter the afferent lymph within 4 h. Interestingly, the addition of CpG, a bacterial pathogenassociated molecular pattern, increased the total number of neutrophils leaving the injection site but did not significantly prolong the duration of a nonspecific neutrophil-associated inflammatory response at the site of injection.…”

Section: Discussionmentioning

confidence: 87%

“…From our data, it appears that this is occurring in vivo within the peripheral tissues prior to emigration to the lymph node, but only with monocytes that have taken up the Ag, presumably in concert with CpG within the liposomes. Of the vaccine adjuvants we have tested within ovine lymphatics (26,28,33), CpG uniquely triggers Ag-carrying monocytes and DCs to increase their T cell-activating machinery at the injection site before migrating to the local lymph node. Taken together with increased DC Ag uptake over the vaccination time course, these results may provide an explanation for the increased Ag-specific adaptive immunity induced by CpG (18,19,42).…”

Section: Discussionmentioning

confidence: 99%

“…Ovine prefemoral pseudoafferent and efferent lymphatic cannulations were performed as previously described (26,27). For pseudoafferent lymphatic cannulation, the prefemoral lymph nodes of merino sheep were removed at 1 y of age, and at least 2 mo was allowed for reanastomosis of the afferent lymphatics with the larger efferent lymphatic vessel.…”

Section: Pseudoafferent and Efferent Lymphatic Cannulation Surgerymentioning

confidence: 99%

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Incorporation of CpG into a Liposomal Vaccine Formulation Increases the Maturation of Antigen-Loaded Dendritic Cells and Monocytes To Improve Local and Systemic Immunity

Neeland

Elhay²,

Nathanielsz³

et al. 2014

The Journal of Immunology

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Liposomal vaccine formulations incorporating stimulants that target innate immune receptors have been shown to significantly increase vaccine immunity. Following vaccination, innate cell populations respond to immune stimuli, phagocytose and process Ag, and migrate from the injection site, via the afferent lymphatic vessels, into the local lymph node. In this study, the signals received in the periphery promote and sculpt the adaptive immune response. Effector lymphocytes then leave the lymph node via the efferent lymphatic vessel to perform their systemic function. We have directly cannulated the ovine lymphatic vessels to detail the in vivo innate and adaptive immune responses occurring in the local draining lymphatic network following vaccination with a liposome-based delivery system incorporating CpG. We show that CpG induces the rapid recruitment of neutrophils, enhances dendritic cell–associated Ag transport, and influences the maturation of innate cells entering the afferent lymph. This translated into an extended period of lymph node shutdown, the induction of IFN-γ–positive T cells, and enhanced production of Ag-specific Abs. Taken together, the results of this study quantify the real-time in vivo kinetics of the immune response in a large animal model after vaccination of a dose comparable to that administered to humans. This study details enhancement of numerous immune mechanisms that provide an explanation for the immunogenic function of CpG when employed as an adjuvant within vaccines.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Pseudoafferent and Efferent Lymphatic Cannulation Surgerymentioning

confidence: 99%

See 2 more Smart Citations

Incorporation of CpG into a Liposomal Vaccine Formulation Increases the Maturation of Antigen-Loaded Dendritic Cells and Monocytes To Improve Local and Systemic Immunity

Neeland

Elhay²,

Nathanielsz³

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, the draining lymphatic vessels actively participate in the homing and maturation of dendritic cells (DC) during the early steps of immune activation. This understanding has guided new strategies for the evaluation of the mechanisms of action of adjuvants [16] and for improvements in vaccine delivery [13].…”

Section: Lymphatic Drainagementioning

confidence: 99%

An approach to local immunotoxicity induced by adjuvanted vaccines

Batista-Duharte¹,

Portuondo

Carlos

et al. 2013

International Immunopharmacology

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Vaccine adjuvants for infectious disease in the clinic

Goetz,

Thotathil,

Zhao

et al. 2024

Bioengineering & Transla Med

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Adjuvants, materials added to vaccines to enhance the resulting immune response, are important components of vaccination that are many times overlooked. While vaccines always include an antigen to tell the body what to vaccinate to, of equal importance the adjuvant provides the how, a significant factor in producing a complete response. The adjuvant space has been slow to develop with the first use of an adjuvant in a licensed vaccine occurring in the 1930s, and remaining the only adjuvant in licensed vaccines for the next 80 years. However, with vaccination at the forefront of protection against new and complex pathogens, it is important to consider all components when designing an effective vaccine. Here we summarize the adjuvant space in licensed vaccines as well as the novel adjuvant space in clinical trials with a specific focus on the materials utilized and their resulting impact on the immune response. We discuss five major categories of adjuvant materials: aluminum salts, nanoparticles, viral vectors, TLR agonists, and emulsions. For each category, we delve into the current clinical trials space, the impact of these materials on vaccination, as well as some of the ways in which they could be improved. Adjuvants present an exciting opportunity to improve vaccine responses and stability, this review will help inform about the current progress of this space.Translational impact statementIn the aftermath of the COVID‐19 pandemic, vaccines for infectious diseases have come into the spotlight. While antigens have always been an important focus of vaccine design, the adjuvant is a significant tool for enhancing the immune response to the vaccine that has been largely underdeveloped. This article provides a broad review of the history of adjuvants and, the current vaccine adjuvant space, and the progress seen in adjuvants in clinical trials. There is specific emphasis on the material landscape for adjuvants and their resulting mechanism of action. Looking ahead, while the novel vaccine adjuvant space features exciting new technologies and materials, there is still a need for more to meet the protective needs of new and complex pathogens.

show abstract

The kinetics of soluble and particulate antigen trafficking in the afferent lymph, and its modulation by aluminum-based adjuvant

Cited by 57 publications

References 23 publications

Incorporation of CpG into a Liposomal Vaccine Formulation Increases the Maturation of Antigen-Loaded Dendritic Cells and Monocytes To Improve Local and Systemic Immunity

Incorporation of CpG into a Liposomal Vaccine Formulation Increases the Maturation of Antigen-Loaded Dendritic Cells and Monocytes To Improve Local and Systemic Immunity

An approach to local immunotoxicity induced by adjuvanted vaccines

Vaccine adjuvants for infectious disease in the clinic

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