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Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies.

Wang S, Liu H, Zhang X, Qian F - Protein Cell (2015)

Bottom Line: Most pathogens initiate their infections at the human mucosal surface.Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development.However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Medicine and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, 100084, China.

ABSTRACT
Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of mucosal immunity. Ag: antigen; M: M cells; SIgA: secretory IgA
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Related In: Results  -  Collection


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Fig1: Schematic illustration of mucosal immunity. Ag: antigen; M: M cells; SIgA: secretory IgA

Mentions: The mucosal surface is protected by the large and specialized innate and adaptive mucosal immune system. Innate immune system plays an important role in fighting against initial infections and facilitating generation of adaptive immune response, while adaptive immune system is vital for providing protection against previously encountered pathogens. The mucosal immunization occurs at the inductive sites called the mucosa-associated lymphoid tissue (MALT), which contains B cells, T cells and antigen presenting cells (APCs) for specific immune response initiation (Holmgren and Czerkinsky, 2005; Lawson et al., 2011). The MALT is covered by a follicle-associated epithelium, comprising epithelium cells, lymphoid cells and a minor portion of microfold/membraneous (M) cells (Fig. 1). M cells are generally recognized as the antigen uptaking cells from the lumen of intestinal/nasal mucosa and transport antigens to the underlying APCs in MALT. Upon infection or vaccination, precursor cells (B cell, T cell and dendritic cells) in inductive sites can be activated, and then migrate and populate the local or remote mucosa sites through the common mucosal immune system to realize the systemic immune protection. Most mucosal response occurs at the local initiation and adjacent interconnected mucosa. As an exception, intranasal vaccination could induce IgA secretion not only at local nasal and adjacent oral mucosa surface, but also remote vaginal and rectal regions (Holmgren and Czerkinsky, 2005).Figure 1


Intranasal and oral vaccination with protein-based antigens: advantages, challenges and formulation strategies.

Wang S, Liu H, Zhang X, Qian F - Protein Cell (2015)

Schematic illustration of mucosal immunity. Ag: antigen; M: M cells; SIgA: secretory IgA
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491048&req=5

Fig1: Schematic illustration of mucosal immunity. Ag: antigen; M: M cells; SIgA: secretory IgA
Mentions: The mucosal surface is protected by the large and specialized innate and adaptive mucosal immune system. Innate immune system plays an important role in fighting against initial infections and facilitating generation of adaptive immune response, while adaptive immune system is vital for providing protection against previously encountered pathogens. The mucosal immunization occurs at the inductive sites called the mucosa-associated lymphoid tissue (MALT), which contains B cells, T cells and antigen presenting cells (APCs) for specific immune response initiation (Holmgren and Czerkinsky, 2005; Lawson et al., 2011). The MALT is covered by a follicle-associated epithelium, comprising epithelium cells, lymphoid cells and a minor portion of microfold/membraneous (M) cells (Fig. 1). M cells are generally recognized as the antigen uptaking cells from the lumen of intestinal/nasal mucosa and transport antigens to the underlying APCs in MALT. Upon infection or vaccination, precursor cells (B cell, T cell and dendritic cells) in inductive sites can be activated, and then migrate and populate the local or remote mucosa sites through the common mucosal immune system to realize the systemic immune protection. Most mucosal response occurs at the local initiation and adjacent interconnected mucosa. As an exception, intranasal vaccination could induce IgA secretion not only at local nasal and adjacent oral mucosa surface, but also remote vaginal and rectal regions (Holmgren and Czerkinsky, 2005).Figure 1

Bottom Line: Most pathogens initiate their infections at the human mucosal surface.Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development.However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Medicine and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, 100084, China.

ABSTRACT
Most pathogens initiate their infections at the human mucosal surface. Therefore, mucosal vaccination, especially through oral or intranasal administration routes, is highly desired for infectious diseases. Meanwhile, protein-based antigens provide a safer alternative to the whole pathogen or DNA based ones in vaccine development. However, the unique biopharmaceutical hurdles that intranasally or orally delivered protein vaccines need to overcome before they reach the sites of targeting, the relatively low immunogenicity, as well as the low stability of the protein antigens, require thoughtful and fine-tuned mucosal vaccine formulations, including the selection of immunostimulants, the identification of the suitable vaccine delivery system, and the determination of the exact composition and manufacturing conditions. This review aims to provide an up-to-date survey of the protein antigen-based vaccine formulation development, including the usage of immunostimulants and the optimization of vaccine delivery systems for intranasal and oral administrations.

No MeSH data available.


Related in: MedlinePlus