BCG vaccination improves DTaP immune responses in mice and is associated with lower pertussis incidence in ecological epidemiological studies
Esther Broset,
Jacobo Pardo-Seco,
Alex I. Kanno,
Nacho Aguilo,
Ana Isabel Dacosta,
Irene Rivero-Calle,
Jesus Gonzalo-Asensio,
Camille Locht,
Luciana C.C. Leite,
Carlos Martin,
Federico Martinón-Torres
Affiliations
Esther Broset
Grupo de Genetica de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragón, Zaragoza 50009, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Corresponding author.
Jacobo Pardo-Seco
Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain; GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago (SERGAS), University of Santiago de Compostela, Galicia, Spain
Alex I. Kanno
Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, Av. Vital Brasil 1500, São Paulo 05503-900, Brazil
Nacho Aguilo
Grupo de Genetica de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragón, Zaragoza 50009, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
Ana Isabel Dacosta
Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain; GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago (SERGAS), University of Santiago de Compostela, Galicia, Spain
Irene Rivero-Calle
Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain; GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago (SERGAS), University of Santiago de Compostela, Galicia, Spain
Jesus Gonzalo-Asensio
Grupo de Genetica de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragón, Zaragoza 50009, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Zaragoza, Spain
Camille Locht
Center of Infection and Immunity of Lille, Institut Pasteur de Lille, Lille 59019, France; Inserm U1019, Lille 59019, France; CNRS UMR8204, Lille 59019, France; Univ. Lille, Lille 59019, France
Luciana C.C. Leite
Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, Av. Vital Brasil 1500, São Paulo 05503-900, Brazil
Carlos Martin
Grupo de Genetica de Micobacterias, Departamento de Microbiología y Medicina Preventiva, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragón, Zaragoza 50009, Spain; CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; Servicio de Microbiología, Hospital Universitario Miguel Servet, IIS Aragón, Zaragoza, Spain
Federico Martinón-Torres
Translational Pediatrics and Infectious Diseases, Pediatrics Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain; GENVIP Research Group (www.genvip.org), Instituto de Investigación Sanitaria de Santiago (SERGAS), University of Santiago de Compostela, Galicia, Spain
Background: The Bacillus Calmette-Guérin (BCG), the only vaccine against tuberculosis (TB) currently in use, has shown beneficial effects against unrelated infections and to enhance immune responses to vaccines. However, there is little evidence regarding the influence of BCG vaccination on pertussis. Methods: Here, we studied the ability of BCG to improve the immune responses to diphtheria, tetanus, and acellular (DTaP) or whole-cell pertussis (DTwP) vaccination in a mouse model. We included MTBVAC, an experimental live-attenuated vaccine derived from Mycobacterium tuberculosis, in our studies to explore if it presents similar heterologous immunity as BCG. Furthermore, we explored the potential effect of routine BCG vaccination on pertussis incidence worldwide. Findings: We found that both BCG and MTBVAC when administered before DTaP, triggered Th1 immune responses against diphtheria, tetanus, and pertussis in mice. Immunization with DTaP alone failed to trigger a Th1 response, as measured by the production of IFN-γ. Humoral responses against DTaP antigens were also enhanced by previous immunization with BCG or MTBVAC. Furthermore, exploration of human epidemiological data showed that pertussis incidence was 10-fold lower in countries that use DTaP and BCG compared to countries that use only DTaP. Interpretation: BCG vaccination may have a beneficial impact on the protection against pertussis conferred by DTaP. Further randomized controlled trials are needed to properly define the impact of BCG on pertussis incidence in a controlled setting. This could be a major finding that would support changes in immunization policies. Funding: This work was supported by the Ministry of “Economía y Competitividad”; European Commission H2020 program, “Gobierno de Aragón”; CIBERES; “Fundação Butantan”; Instituto de Salud Carlos III and “Fondo FEDER”.
