Next Generation Mucosal Vaccine Strategy for Respiratory Pathogens
Abstract
:1. Introduction
2. The Mucosa-Associated Lymphoid Tissue
3. Immune Surveillance at Mucosal Surfaces
4. Mucosal Humoral Response
5. Mucosal Cellular Immune Response
6. Inducing Immunity Systemically and at Local Mucosal Sites
7. Modulating Mucosal Immune Responses by Immunization Routes
8. Training Mucosal Innate Immunity
9. Currently Licensed Mucosal Vaccines
10. Nucleic Acid and Subunit Mucosal Vaccines
11. Synthetic Carriers and Routes of Mucosal Vaccine Delivery
12. Live Attenuated Viruses and Viral Vectors for Mucosal Vaccines
13. Improving Mucosal Immune Response by Adjuvants
14. Mucosal Vaccine Lessons from Natural Infections
15. Relevance of Mucosal Vaccination against Respiratory Pathogens
16. Advantages of Adenoviral Vectors in Mucosal Vaccination
17. Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Vaccine | Composition | Pathogen Targeted | Mucosal Route | Approval Year | Approving Authority |
---|---|---|---|---|---|
Bivalent Oral Polio Vaccine (bOPV) | Serotypes 1 and 3 attenuated by serial culture | Poliovirus | Oral drops | 1961 | FDA |
Dukoral | Heat and formaldehyde inactivated O1 (Ogawa and Inaba) with recombinant B subunit of cholera toxin | Vibrio cholerae | Oral drink | 2003 | Canada |
Shanchol | Bivalent heat and formaldehyde inactivated O1 (Ogawa and Inaba) and O139 serotypes | Oral drops | 2013 | WHO | |
Vaxchora | Live O1 Inaba serogroup attenuated by deleting the catalytic domain of the ctxA gene | Oral drink | 2015 | FDA | |
Vivotif | Live Ty21a strain attenuated by mutations in LPS and Vi polysaccharide synthesis genes | Salmonella typhi | Oral capsule | 2013 | FDA |
Rotateq | Live pentavalent reassortant rotaviruses, containing G1, G2, G3, G4, and P1A strains | Rotavirus | Oral drops | 2006 | FDA |
Rotarix | Live monovalent passage attenuated G1 rotavirus strain with P1A expression | Oral Drops | 2008 | FDA | |
Adenovirus vaccine (types 4 and 7) | Live Adenovirus type 4 and type 7 strains | Acute Ad4 and Ad7 respiratory disease | Oral-2 tablets | 2011 | FDA |
FluMist | Quadrivalent live attenuated (cold-adapted) flu A and B strains | Seasonal Influenza | Nasal-Spray | 2003 | FDA |
iNCOVACC | ChAd36 adenoviral vector expressing the SARS-CoV-2 Spike protein (Wuhan) | SARS-CoV-2 | Intranasal drops | 2022 | Central Drugs Standard Control Organization—India |
Convidecia Air | Ad5 adenoviral vector expressing the SARS-CoV-2 Spike protein (Wuhan) | Inhaled aerosol | 2022 | National Medical Products Administration of China |
Antigen Delivery | Advantage | Disadvantage | References |
---|---|---|---|
mRNA | Synthetic, non-infectious, and free from cellular or egg proteins. | Sensitive to pH and degradation by enzymes. | [71,123,124] |
Short development and manufacturing time. | Inability to penetrate mucus barriers. | ||
Produces high systemic antibody titers. | Adjuvants are required to break mucosal immune tolerance. | ||
Transient expression. | Poor mucosal immune response. | ||
Cannot modify host genome. | Ultra-low cold chain required for storage. | ||
Protein Subunit | Can be lyophilized for good environmental stability. | High antigen requirement. | [71,123] |
Can be used regardless of age or immunocompromised status | Sensitive to pH and degradation by enzymes. | ||
Cannot modify host genome. | Inability to penetrate mucus barriers. | ||
Adjuvants are required to break mucosal immune tolerance. | |||
Poor mucosal immune response. | |||
Complex manufacturing requirements (conjugation chemistry). | |||
Difficult to isolate the most relevant antigens. | |||
Live Viral | Well-established technology. Better stability than mRNA vaccines. | Complex manufacturing and safety requirements. | [71,123,125] |
Naturally capable of penetrating mucus barriers, tolerating high/low pH, and infecting target cells. | Cannot be given to immunocompromised patients. | ||
Induces strong mucosal and systemic immune responses. | Small chance of reverting to a pathogenic form and causing disease. | ||
May not need adjuvants | Takes time to develop. | ||
Simple to manufacture. | |||
Viral Vector | Induces strong mucosal and systemic immune responses. | Concerns for host genome modification/integration. | [71,123,126] |
Naturally capable of penetrating mucus barriers, tolerating high/low pH, and infecting target cells. | Complex manufacturing and safety requirements. | ||
May not need adjuvants. Better stability than mRNA vaccines. | Response reduced due to pre-existing immunity against the vector. | ||
Simple to manufacture. | Takes time to develop. | ||
Cannot cause diseases like live attenuated viruses. |
Class | Molecule/Mechanism | Immune Cell Target | Patents |
---|---|---|---|
Bacterial Toxins | Double-mutant Labile Toxin | Dendritic cell, Macrophages, M cells | US6033673A |
Cholera Toxin | Dendritic cell, CD4+ T cells | WO2001062283A2 | |
Cholera Toxin A1-dimer D-domain (S. aureus) | Dendritic cell, Macrophages, CD4+ T cells | US8834898B2 | |
α-Galactosylceramide | CD1 binding | Dendritic cell, CD8+ T cells | WO2007007946A1 |
TLR ligands | MPL—TLR4 | Dendritic cell, Macrophages | US20170182152A1 |
CpG—TLR9 | B cells, Plasma cells | US6589940B1 | |
Flagellin—TLR5 | Dendritic cell, Macrophages | US7404963B2 | |
Cytokines | IL-1, IL-12, IL-18, GM-CSF, RANTES | CD8+ T cells, B cells—IgA, Monocytes, Natural Killer cells, CD4+ and CD8+ T cells | US6168923B1 |
US5800810A | |||
EP1075275A1 | |||
US5679356A | |||
Chitosan | Mucoadhesive, improves antigen uptake | Dendritic cell, Macrophages, Natural Killer cells | CN107648603B |
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Dotiwala, F.; Upadhyay, A.K. Next Generation Mucosal Vaccine Strategy for Respiratory Pathogens. Vaccines 2023, 11, 1585. https://doi.org/10.3390/vaccines11101585
Dotiwala F, Upadhyay AK. Next Generation Mucosal Vaccine Strategy for Respiratory Pathogens. Vaccines. 2023; 11(10):1585. https://doi.org/10.3390/vaccines11101585
Chicago/Turabian StyleDotiwala, Farokh, and Arun K. Upadhyay. 2023. "Next Generation Mucosal Vaccine Strategy for Respiratory Pathogens" Vaccines 11, no. 10: 1585. https://doi.org/10.3390/vaccines11101585