Strategies to Develop a Mucosa-Targeting Vaccine against Emerging Infectious Diseases

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.

Injectable Hydrogel Mucosal Vaccine Elicits Protective Immunity against Respiratory Viruses

“…55, 56 Self-healing hydrogels can be adapted to create multiple types of mucosal vaccines by adjusting the mucosal injection sites to gastrointestinal, respiratory, genitourinary, and ocular cavities. 57 The development of mucosal delivery devices remains indispensable, as these provide optimal and reproducible dosing, convenient packaging, and the ability to be refilled. 58 Additionally, the nasal route of administration carries the convenience of penetrating the blood−brain barrier; self-healing hydrogels also hold great promise for treating brain disorders, such as psychiatric diseases or brain malignancies.…”

Rapid Induction of Long-Lasting Systemic and Mucosal Immunity via Thermostable Microneedle-Mediated Chitosan Oligosaccharide-Encapsulated DNA Nanoparticles

“…Impressively, our data supported that these MN-delivered DNA@COS NPs had the potential to elicit a strong immune response at local mucosal tissue, as evidenced by the high frequency of SARS-CoV-2-specific IFN-γ + T cells in the lung tissue and the high level of S-specific IgA antibodies in serum. It is well known that many pathogens enter our bodies mainly through mucosal surfaces, including the respiratory tract, skin epithelium, and reproductive tract, and therefore mucosal immunity is usually considered as the first line of defense against such infectious pathogens . As a result, it is necessary to develop the next generation of mucosal vaccines to confer superior protection by eliciting mucosal immunity.…”

“…To date, the World Health Organization has approved at least fifteen COVID-19 vaccines for clinical use, with the majority administered via intramuscular injection (IM). However, there are several disadvantages to IM-based vaccination, which usually requires strict storage conditions under cold-chain distribution and professional administration by medical personnel and typically results in weak mucosal immunity. − In addition, many people are reluctant to receive this vaccine modality due to fear of needles, stemming from the trauma and pain associated with IM. , The COVID-19 pandemic has emphasized the urgent need for a platform that can rapidly develop mucosa-targeted vaccine technology. Therefore, it is of great significance to explore alternative vaccine modalities that can improve effectiveness and coverage of vaccination across different populations.…”

Macrophage-infectivity potentiator of Trypanosoma cruzi (TcMIP) is a new pro-type 1 immuno-stimulating protein for neonatal human cells and vaccines in mice

“…Accordingly, neonates are also less prone to mount protective type 1 immune responses to vaccines. This highlights the need for pro-type 1 adjuvants for protein and peptide-based vaccines ( 3 , 35 , 36 ) to complement the limited number of adjuvants that are currently approved for human use ( 1 , 2 ). In this context, our present work resulted in the discovery of a candidate pro-type 1 vaccinal adjuvant for pediatric vaccines.…”