1. An intranasal nanoparticle vaccine elicits protective immunity against Mycobacterium tuberculosis.
- Author
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Sefat KMSR, Kumar M, Kehl S, Kulkarni R, Leekha A, Paniagua MM, Ackart DF, Jones N, Spencer C, Podell BK, Ouellet H, and Varadarajan N
- Subjects
- Animals, Mice, Adjuvants, Immunologic administration & dosage, Female, Tuberculosis prevention & control, Tuberculosis immunology, Lung immunology, Lung microbiology, Bacterial Proteins immunology, Acyltransferases immunology, Acyltransferases genetics, CD4-Positive T-Lymphocytes immunology, Adjuvants, Vaccine administration & dosage, Immunity, Mucosal immunology, Nanovaccines, Recombinant Fusion Proteins, Tuberculosis Vaccines immunology, Tuberculosis Vaccines administration & dosage, Administration, Intranasal, Mycobacterium tuberculosis immunology, Nanoparticles administration & dosage, Nanoparticles chemistry, Antigens, Bacterial immunology, Antigens, Bacterial administration & dosage, Mice, Inbred C57BL
- Abstract
Mucosal vaccines have the potential to elicit protective immune responses at the point of entry of respiratory pathogens, thus preventing even the initial seed infection. Unlike licensed injectable vaccines, mucosal vaccines comprising protein subunits are only in development. One of the primary challenges associated with mucosal vaccines has been identifying and characterizing safe yet effective mucosal adjuvants that can effectively prime multi-factorial mucosal immunity. In this study, we tested NanoSTING, a liposomal formulation of the endogenous activator of the stimulator of interferon genes (STING) pathway, cyclic guanosine adenosine monophosphate (cGAMP), as a mucosal adjuvant. We formulated a vaccine based on the H1 antigen (fusion protein of Ag85b and ESAT-6) adjuvanted with NanoSTING. Intranasal immunization of NanoSTING-H1 elicited a strong T-cell response in the lung of vaccinated animals characterized by (a) CXCR3
+ KLRG1- lung resident T cells that are known to be essential for controlling bacterial infection, (b) IFNγ-secreting CD4+ T cells which is necessary for intracellular bactericidal activity, and (c) IL17-secreting CD4+ T cells that can confer protective immunity against multiple clinically relevant strains of Mtb. Upon challenge with aerosolized Mycobacterium tuberculosis Erdman strain, intranasal NanoSTING-H1 provides protection comparable to subcutaneous administration of the live attenuated Mycobacterium bovis vaccine strain Bacille-Calmette-Guérin (BCG). Our results indicate that NanoSTING adjuvanted protein vaccines can elicit a multi-factorial immune response that protects from infection by M. tuberculosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Navin Varadarajan reports financial support was provided by National Institutes of Health. Navin Varadarajan reports financial support was provided by AuraVax Therapeutics. Navin Varadarajan reports a relationship with AuraVax Therapeutics and CellChorus that includes: equity or stocks., (Copyright © 2024. Published by Elsevier Ltd.)- Published
- 2024
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