Respiratory immunization with a whole cell inactivated vaccine induces functional mucosal immunoglobulins against tuberculosis in mice and non-human primates

Aguilo, N. (Universidad de Zaragoza) ; Uranga, S. (Universidad de Zaragoza) ; Mata, E. (Universidad de Zaragoza) ; Tarancon, R. (Universidad de Zaragoza) ; Gómez, A.B. (Universidad de Zaragoza) ; Marinova, D. (Universidad de Zaragoza) ; Otal, I. (Universidad de Zaragoza) ; Monzón, M. (Universidad de Zaragoza) ; Badiola, J. (Universidad de Zaragoza) ; Montenegro, D. ; Puentes, E. ; Rodríguez, E. ; Vervenne, R.A.W. ; Sombroek, C.C. ; Verreck, F.A.W. ; Martín, C. (Universidad de Zaragoza)

Resumen: 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 vitro assays demonstrated the functionality of these immunoglobulins to induce M. tuberculosis opsonization 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.

Idioma: Inglés

DOI: 10.3389/fmicb.2020.01339

Año: 2020

Publicado en: Frontiers in Microbiology 11 (2020), 1339 [15 pp.]
ISSN: 1664-302X

Factor impacto JCR: 5.64 (2020)

Categ. JCR: MICROBIOLOGY rank: 28 / 135 = 0.207 (2020) - Q1 - T1

Factor impacto SCIMAGO: 1.701 - Microbiology (medical) (Q1) - Microbiology (Q1)

Financiación: info:eu-repo/grantAgreement/EC/H2020/643381/EU/TBVAC2020; Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development/TBVAC2020
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-097625-B-100
Financiación: info:eu-repo/grantAgreement/ES/MINECO/IPT2012-0327-090000

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Microbiología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Proy. investigación HQA (Dpto. Microb.Ped.Radio.Sal.Pú.)