Journal
FRONTIERS IN MICROBIOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmicb.2020.01339
Keywords
whole-cell vaccine; pulmonary vaccination; animal models; mucosal immunoglobulins; opsonization; tuberculosis
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Funding
- Spanish Ministry of Economy and Competitiveness [IPT-2012-0327-090000]
- Ministry of Science, Innovation and Universities [RTI2018-097625-B-I00]
- European Commission H2020 program [TBVAC2020 643381]
- Gobierno de Aragon/Fondo Social Europeo
- Bill and Melinda Gates Foundation (BMGF)
- BPRC
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Vaccination through the natural route of infection represents an attractive immunization strategy in vaccinology. In the case of tuberculosis, vaccine delivery by the respiratory route has regained interest in recent years, showing efficacy in different animal models. In this context, respiratory vaccination triggers lung immunological mechanisms which are omitted when vaccines are administered by parenteral route. However, contribution of mucosal antibodies to vaccine- induced protection has been poorly studied. In the present study, we evaluated in mice and non-human primates (NHP) a novel whole cell inactivated vaccine (MTBVAC HK), by mucosal administration. MTBVAC HK given by intranasal route to BCG-primed mice substantially improved the protective efficacy conferred by subcutaneous BCG only. Interestingly, this improved protection was absent in mice lacking polymeric Ig receptor (pIgR), suggesting a crucial role of mucosal secretory immunoglobulins in protective immunity. Our study in NHP confirmed the ability of MTBVAC HK to trigger mucosal immunoglobulins. Importantly,in vitroassays demonstrated the functionality of these immunoglobulins to induceM. tuberculosisopsonization in the presence of human macrophages. Altogether, our results suggest that mucosal immunoglobulins can be induced by vaccination to improve protection against tuberculosis and therefore, they represent a promising target for next generation tuberculosis vaccines.
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