Journal article
Induction of mycobacterial protective immunity by sublingual BCG vaccination
Vaccine, Vol.37(36), pp.5364-5370
08/23/2019
DOI: 10.1016/j.vaccine.2019.07.034
PMID: 31331776
Abstract
•Sublingual BCG induces strong mycobacteria-specific T cell responses in mice.•Sublingual BCG vaccination induces robust and durable protective immunity.•Sublingual BCG vaccination fails to induce potent mycobacteria-specific antibodies.•BCG dissemination is less pronounced after sublingual than intranasal delivery.
Tuberculosis (TB) remains a tremendous global health problem, with 1/4 of the world’s population infected and causing > 1 million deaths annually. Intradermal Bacillus Calmette-Guérin (BCG) vaccine given during infancy protects against severe forms of acute disease but does not prevent chronic infection or development of pulmonary TB. TB vaccine mucosal targeting potentially could induce mucosal resident immune cells with increased protective capacity against pulmonary infection and disease. Sublingual (SL) administration of vaccines may be an optimal mucosal delivery platform based on the high absorptive capacity of this mucosal surface, the extensive lymphoid tissue, and published preclinical studies demonstrating efficacy of SL vaccination against other pathogens. To this end, we performed preliminary testing of sublingual TB vaccines. Vaccination of mice with SL BCG elicited potent mycobacteria-specific T cell responses which persisted 16 weeks post-immunization. The magnitudes of the T cell responses were similarly induced after sublingual, intranasal, and subcutaneous BCG vaccination. Interestingly, serum mycobacteria-specific antibody responses and systemic recovery of BCG post-vaccination were lower after SL BCG compared with systemic BCG immunization. However, more importantly, SL BCG vaccinated mice were significantly protected against an aerosolized virulent M. tuberculosis challenge (P < 0.0001 compared to unvaccinated mice). Furthermore, this protection was long-lived, persisting for 16 weeks with >1 log CFU reduction compared with naïve challenged mice in both lungs and spleens (P < 0.0001 and P < 0.0028, respectively). These exciting results provide strong support for further studies exploring the mechanisms of protective immunity induced by sublingual BCG vaccination.
Details
- Title: Subtitle
- Induction of mycobacterial protective immunity by sublingual BCG vaccination
- Creators
- Christopher S. Eickhoff - Saint Louis UniversityAzra Blazevic - Saint Louis UniversityEmma A. Killoran - Washington University in St. LouisMary S. Morris - ENT and AllergyDaniel F. Hoft - Saint Louis University
- Resource Type
- Journal article
- Publication Details
- Vaccine, Vol.37(36), pp.5364-5370
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.vaccine.2019.07.034
- PMID
- 31331776
- ISSN
- 0264-410X
- eISSN
- 1873-2518
- Number of pages
- 7
- Language
- English
- Date published
- 08/23/2019
- Academic Unit
- Dermatology
- Record Identifier
- 9984719846302771
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