Abstract

Numerous pathogenic microbes, including viruses, bacteria, and fungi, usually infect the host through the mucosal surfaces of the respiratory tract, gastrointestinal tract, and reproductive tract. The mucosa is well known to provide the first line of host defense against pathogen entry by physical, chemical, biological, and immunological barriers, and therefore, mucosa-targeting vaccination is emerging as a promising strategy for conferring superior protection. However, there are still many challenges to be solved to develop an effective mucosal vaccine, such as poor adhesion to the mucosal surface, insufficient uptake to break through the mucus, and the difficulty in avoiding strong degradation through the gastrointestinal tract. Recently, increasing efforts to overcome these issues have been made, and we herein summarize the latest findings on these strategies to develop mucosa-targeting vaccines, including a novel needle-free mucosa-targeting route, the development of mucosa-targeting vectors, the administration of mucosal adjuvants, encapsulating vaccines into nanoparticle formulations, and antigen design to conjugate with mucosa-targeting ligands. Our work will highlight the importance of further developing mucosal vaccine technology to combat the frequent outbreaks of infectious diseases.

Highlights

  • The frequent emergence and re-emergence of highly pathogenic microbes have become a severe threat for human public health, including severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, avian influenza, Ebola virus (EBOV), human immunodeficiency virus (HIV), and mycobacterium tuberculosis (TB)

  • Environments, and mucopolysaccharides; the microbiomes and their metabolites constitute a biological barrier; the mucosal immune barrier is mainly formed by secretory IgA, cytokines, mucosa-associated lymphoid tissue (MALT), and diffused innate and adaptive immunocytes [1]

  • The clinically available vaccines are mostly aimed at inducing systemic immune responses, and only a very few licensed vaccines are designed to elicit local mucosal immunity instead

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Summary

Mucosal Defense against Pathogenic Microbes

The frequent emergence and re-emergence of highly pathogenic microbes have become a severe threat for human public health, including severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, avian influenza, Ebola virus (EBOV), human immunodeficiency virus (HIV), and mycobacterium tuberculosis (TB). MALT is folliclepredominantly formed by B‐cell‐dependent embedded in a netwo associated epithelium (FAE) containing morphologically distinct cells named “microfold” or dendritic cells (FDC); CD4+ T lymphocytes and macrophages, and T‐cell‐d “membrane” (M), which are specialized in exogenous antigen sampling from the mucosal follicular areas some predominantly containing. Given that the mucosal immune system has substantial roles in combating pathogenic microbes, the generation of vaccines effectively primed and migrate from the MALT to the peripheral blood, an should focus on developing mucosa-targeting vaccines to effectively induce mucosal immune they are extravasated at the mucosal epithelium throughout the whole bo responses to confer superior protection. Given that the mucosal immune system has substanti bating pathogenic microbes, the generation of vaccines should focus mucosa‐targeting vaccines to effectively induce mucosal immune respons

Challenges and Solutions for the Development of Mucosa-Targeting Vaccines
Antigen Administration through Needle-Free Mucosal Route to Induce Mucosal
Development of Mucosal Adjuvants to Enhance the Effectiveness of Mucosa-Targeting Vaccines
Construction of Novel Vectors as Mucosa-Targeting Vaccines
Nanoparticle-Based Formulation to Reshape the Vaccine–Host Cell Recognition and Then
Antigen Design to Conjugate with Mucosa-Targeting Ligands
Conclusions and Perspective
China 2006, 86, 3109–3113
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