title: A novel live vector group A streptococcal emm type 9 vaccine delivered intranasally protects mice against challenge infection with emm type 9 group A streptococci.
abstract: The availability of a protective vaccine against Streptococcus pyogenes (group A Streptococcus [GAS]) is a priority for public health worldwide. Here, we have generated six live vaccine strains, each engineered to express an N-terminal M protein peptide from one of six of the most prevalent emm types of GAS (M1, M2, M4, M9, M12, and M28). The vaccine strains are based on a food-grade Lactococcus lactis strain and do not bear any antibiotic resistance. Mice immunized with the vaccine strain expressing the M9 peptide (termed here the L. lactis M9 strain) showed high titers of serum antibodies when delivered intranasally. Mice immunized with the L. lactis M9 strain were protected against infection after intranasal challenge with type 9 streptococci. Several parameters of disease, such as weight loss, body temperature, colony counts in mouth washes, and lung histology, were significantly improved in immunized mice compared to naive control mice. Our results indicate that intranasal delivery of the L. lactis M9 strain live bacterial vaccine induced GAS-specific IgG titers, prevented pharyngeal colonization of GAS, and protected mice from disease upon challenge. The design of this vaccine prototype may provide a lower cost alternative to vaccines comprised of purified recombinant proteins.
authors: Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile aniela.wozniak@gmail.com.
authors: Aniela
authors: A
authors: Wozniak
authors: Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Patricia
authors: P
authors: García
authors: Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Enrique A
authors: EA
authors: Geoffroy
authors: Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Daniel B
authors: DB
authors: Aguirre
authors: Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Samantha A
authors: SA
authors: González
authors: Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Victoria A
authors: VA
authors: Sarno
authors: Department of Veterans Affairs Medical Center and Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors: James B
authors: JB
authors: Dale
authors: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Francisco J
authors: FJ
authors: Salazar-Echegarai
authors: Laboratorio de Microbiología, Departamento de Laboratorios Clínicos, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Andrea
authors: A
authors: Vera
authors: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Susan M
authors: SM
authors: Bueno
authors: Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile Departamento de Inmunología y Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors: Alexis M
authors: AM
authors: Kalergis
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D058491:Bacterial Load; D001835:Body Weight; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005334:Fever; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000097:blood; D013294:Lactococcus lactis / Q000235:genetics*; D008168:Lung / Q000473:pathology; D008807:Mice, Inbred BALB C; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D004337:Drug Carriers; D007074:Immunoglobulin G; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic