Buccal and sublingual vaccine delivery

Drug Delivery Technolog

Activation of human monocytes by colloidal aluminium salts

Subunit vaccines often contain colloidal aluminium salt-based adjuvants to activate the innate immune system. These aluminium salts consist of micrometre-sized aggregates. It is well known that particle size affects the adjuvant effect of particulate adjuvants. In this study, the activation of human monocytes by hexagonal-shaped gibbsite (ø=210±40 nm) and rod-shaped boehmite (ø= 83±27 nm) was compared with classical aluminium oxyhydroxide adjuvant (alum). To this end, human primary monocytes were cultured in the presence of alum, gibbsite or boehmite. The transcriptome and proteome of the monocytes were investigated by using quantitative polymerase chain reaction and mass spectrometry. Human monocytic THP-1 cells were used to investigate the effect of the particles on cellular maturation, differentiation, activation and cytokine secretion, as measured by flow cytometry and enzyme-linked immuno sorbent assay. Each particle type resulted in a specific gene expression profile. IL-1ß and IL-6 secretion was significantly upregulated by boehmite and alum. Of the seven surface markers investigated, only CD80 was significantly upregulated by alum and none by gibbsite or boehmite. Gibbsite hardly activated the monocytes. Boehmite activated human primary monocytes equally to alum, but induced a much milder stress-related response. Therefore, boehmite was identified as a promising adjuvant candidate

Aluminum Hydroxide And Aluminum Phosphate Adjuvants Elicit A Different Innate Immune Response

Aluminum hydroxide (Al(OH) 3) and aluminum phosphate (AlPO 4) are widely used adjuvants in human vaccines. However, a rationale to choose one or the other is lacking since the differences between molecular mechanisms of action of these adjuvants are unknown. In the current study, we compared the innate immune response induced by both adjuvants in vitro and in vivo. Proteome analysis of human primary monocytes was used to determine the immunological pathways activated by these adjuvants. Subsequently, analysis of immune cells present at the site of injection and proteome analysis of the muscle tissue revealed the differentially regulated processes related to the innate immune response in vivo. Incubation with Al(OH) 3 specifically enhanced the activation of antigen processing and presentation pathways in vitro. In vivo experiments showed that only intramuscular (I.M.) immunization with Al(OH) 3 attracted neutrophils, while I.M. immunization with AlPO 4 attracted monocytes/macrophages to the site of injection. In addition, only I.M. immunization with Al(OH) 3 enhanced the process of hemostasis after 96 hours, possibly related to neutrophilic extracellular trap formation. Both adjuvants differentially regulated various immune system-related processes. The results show that Al(OH) 3 and AlPO 4 act differently on the innate immune system. We speculate that these different regulations affect the interaction with cells, due to the different physicochemical properties of both adjuvants

Activation of Human Monocytes by Colloidal Aluminum Salts.

Subunit vaccines often contain colloidal aluminum salt-based adjuvants to activate the innate immune system. These aluminum salts consist of micrometer-sized aggregates. It is well-known that particle size affects the adjuvant effect of particulate adjuvants. In this study, the activation of human monocytes by hexagonal-shaped gibbsite (ø = 210 ± 40 nm) and rod-shaped boehmite (ø = 83 ± 827 nm) was compared with classical aluminum oxyhydroxide adjuvant (alum). To this end, human primary monocytes were cultured in the presence of alum, gibbsite, or boehmite. The transcriptome and proteome of the monocytes were investigated by using quantitative polymerase chain reaction and mass spectrometry. Human monocytic THP-1 cells were used to investigate the effect of the particles on cellular maturation, differentiation, activation, and cytokine secretion, as measured by flow cytometry and enzyme-linked immunosorbent assay. Each particle type resulted in a specific gene expression profile. IL-1ß and IL-6 secretion was significantly upregulated by boehmite and alum. Of the 7 surface markers investigated, only CD80 was significantly upregulated by alum and none by gibbsite or boehmite. Gibbsite hardly activated the monocytes. Boehmite activated human primary monocytes equally to alum, but induced a much milder stress-related response. Therefore, boehmite was identified as a promising adjuvant candidate.BiopharmaceuticsDrug Delivery Technolog

Aluminum Hydroxide And Aluminum Phosphate Adjuvants Elicit A Different Innate Immune Response

Aluminum hydroxide (Al(OH) 3) and aluminum phosphate (AlPO 4) are widely used adjuvants in human vaccines. However, a rationale to choose one or the other is lacking since the differences between molecular mechanisms of action of these adjuvants are unknown. In the current study, we compared the innate immune response induced by both adjuvants in vitro and in vivo. Proteome analysis of human primary monocytes was used to determine the immunological pathways activated by these adjuvants. Subsequently, analysis of immune cells present at the site of injection and proteome analysis of the muscle tissue revealed the differentially regulated processes related to the innate immune response in vivo. Incubation with Al(OH) 3 specifically enhanced the activation of antigen processing and presentation pathways in vitro. In vivo experiments showed that only intramuscular (I.M.) immunization with Al(OH) 3 attracted neutrophils, while I.M. immunization with AlPO 4 attracted monocytes/macrophages to the site of injection. In addition, only I.M. immunization with Al(OH) 3 enhanced the process of hemostasis after 96 hours, possibly related to neutrophilic extracellular trap formation. Both adjuvants differentially regulated various immune system-related processes. The results show that Al(OH) 3 and AlPO 4 act differently on the innate immune system. We speculate that these different regulations affect the interaction with cells, due to the different physicochemical properties of both adjuvants

Activation of human monocytes by colloidal aluminium salts

Subunit vaccines often contain colloidal aluminium salt-based adjuvants to activate the innate immune system. These aluminium salts consist of micrometre-sized aggregates. It is well known that particle size affects the adjuvant effect of particulate adjuvants. In this study, the activation of human monocytes by hexagonal-shaped gibbsite (ø=210±40 nm) and rod-shaped boehmite (ø= 83±27 nm) was compared with classical aluminium oxyhydroxide adjuvant (alum). To this end, human primary monocytes were cultured in the presence of alum, gibbsite or boehmite. The transcriptome and proteome of the monocytes were investigated by using quantitative polymerase chain reaction and mass spectrometry. Human monocytic THP-1 cells were used to investigate the effect of the particles on cellular maturation, differentiation, activation and cytokine secretion, as measured by flow cytometry and enzyme-linked immuno sorbent assay. Each particle type resulted in a specific gene expression profile. IL-1ß and IL-6 secretion was significantly upregulated by boehmite and alum. Of the seven surface markers investigated, only CD80 was significantly upregulated by alum and none by gibbsite or boehmite. Gibbsite hardly activated the monocytes. Boehmite activated human primary monocytes equally to alum, but induced a much milder stress-related response. Therefore, boehmite was identified as a promising adjuvant candidate

Buccal and sublingual vaccine delivery

AbstractBecause of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination. An important characteristic of mucosal vaccination is its ability to elicit local immune responses, which act against infection at the site of pathogen entry. However, mucosal surfaces are endowed with potent and sophisticated tolerance mechanisms to prevent the immune system from overreacting to the many environmental antigens. Hence, mucosal vaccination may suppress the immune system instead of induce a protective immune response. Therefore, mucosal adjuvants and/or special antigen delivery systems as well as appropriate dosage forms are required in order to develop potent mucosal vaccines.Whereas oral, nasal and pulmonary vaccine delivery strategies have been described extensively, the sublingual and buccal routes have received considerably less attention. In this review, the characteristics of and approaches for sublingual and buccal vaccine delivery are described and compared with other mucosal vaccine delivery sites. We discuss recent progress and highlight promising developments in the search for vaccine formulations, including adjuvants and suitable dosage forms, which are likely critical for designing a successful sublingual or buccal vaccine. Finally, we outline the challenges, hurdles to overcome and formulation issues relevant for sublingual or buccal vaccine delivery