Biomaterial Database

Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture. 2021

Francisco Carriquiriborde, and Pablo Martin Aispuro, and Nicolás Ambrosis, and Eugenia Zurita, and Daniela Bottero, and María Emilia Gaillard, and Celina Castuma, and Erika Rudi, and Aníbal Lodeiro, and Daniela F Hozbor

Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata, La Plata, Argentina.

Outer membrane vesicles (OMV) derived from Bordetella pertussis-the etiologic agent of the resurgent disease called pertussis-are safe and effective in preventing bacterial colonization in the lungs of immunized mice. Vaccine formulations containing those OMV are capable of inducing a mixed Th1/Th2/Th17 profile, but even more interestingly, they may induce a tissue-resident memory immune response. This immune response is recommended for the new generation of pertussis-vaccines that must be developed to overcome the weaknesses of current commercial acellular vaccines (second-generation of pertussis vaccine). The third-generation of pertussis vaccine should also deal with infections caused by bacteria that currently circulate in the population and are phenotypically and genotypically different [in particular those deficient in the expression of pertactin antigen, PRN(-)] from those that circulated in the past. Here we evaluated the protective capacity of OMV derived from bacteria grown in biofilm, since it was observed that, by difference with older culture collection vaccine strains, circulating clinical B. pertussis isolates possess higher capacity for this lifestyle. Therefore, we performed studies with a clinical isolate with good biofilm-forming capacity. Biofilm lifestyle was confirmed by both scanning electron microscopy and proteomics. While scanning electron microscopy revealed typical biofilm structures in these cultures, BipA, fimbria, and other adhesins described as typical of the biofilm lifestyle were overexpressed in the biofilm culture in comparison with planktonic culture. OMV derived from biofilm (OMVbiof) or planktonic lifestyle (OMVplank) were used to formulate vaccines to compare their immunogenicity and protective capacities against infection with PRN(+) or PRN(-) B. pertussis clinical isolates. Using the mouse protection model, we detected that OMVbiof-vaccine was more immunogenic than OMVplank-vaccine in terms of both specific antibody titers and quality, since OMVbiof-vaccine induced antibodies with higher avidity. Moreover, when OMV were administered at suboptimal quantity for protection, OMVbiof-vaccine exhibited a significantly adequate and higher protective capacity against PRN(+) or PRN(-) than OMVplank-vaccine. Our findings indicate that the vaccine based on B. pertussis biofilm-derived OMV induces high protection also against pertactin-deficient strains, with a robust immune response.

UI	MeSH Term	Description	Entries
D007114	Immunization	Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).	Immunologic Stimulation,Immunostimulation,Sensitization, Immunologic,Variolation,Immunologic Sensitization,Immunological Stimulation,Sensitization, Immunological,Stimulation, Immunologic,Immunizations,Immunological Sensitization,Immunological Sensitizations,Immunological Stimulations,Sensitizations, Immunological,Stimulation, Immunological,Stimulations, Immunological,Variolations
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010566	Virulence Factors, Bordetella	A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.	Bordetella Virulence Factors,Agglutinogen 2, Bordetella Pertussis,Bordetella Virulence Determinant,LFP-Hemagglutinin,LP-HA,Leukocytosis-Promoting Factor Hemagglutinin,Lymphocytosis-Promoting Factor-Hemagglutinin,Pertussis Agglutinins,Agglutinins, Pertussis,Determinant, Bordetella Virulence,Factor Hemagglutinin, Leukocytosis-Promoting,Factor-Hemagglutinin, Lymphocytosis-Promoting,Factors, Bordetella Virulence,Hemagglutinin, Leukocytosis-Promoting Factor,LFP Hemagglutinin,LP HA,Leukocytosis Promoting Factor Hemagglutinin,Lymphocytosis Promoting Factor Hemagglutinin,Virulence Determinant, Bordetella
D010567	Pertussis Vaccine	A suspension of killed Bordetella pertussis organisms, used for immunization against pertussis (WHOOPING COUGH). It is generally used in a mixture with diphtheria and tetanus toxoids (DTP). There is an acellular pertussis vaccine prepared from the purified antigenic components of Bordetella pertussis, which causes fewer adverse reactions than whole-cell vaccine and, like the whole-cell vaccine, is generally used in a mixture with diphtheria and tetanus toxoids. (From Dorland, 28th ed)	Vaccine, Pertussis
D001886	Bordetella pertussis	A species of gram-negative, aerobic bacteria that is the causative agent of WHOOPING COUGH. Its cells are minute coccobacilli that are surrounded by a slime sheath.	Bacterium tussis-convulsivae,Haemophilus pertussis,Hemophilus pertussis
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005260	Female		Females
D000067128	Extracellular Vesicles	Membrane limited structures derived from cell membranes and cytoplasmic material, and released into EXTRACELLULAR SPACE. They circulate through the EXTRACELLULAR FLUID and through the peripheral blood in the MICROVASCULATURE where cells, much larger, cannot, thereby affecting a variety of intercellular communication processes.	Apoptotic Bodies,Exovesicles,Apoptotic Body,Bodies, Apoptotic,Body, Apoptotic,Exovesicle,Extracellular Vesicle,Vesicle, Extracellular,Vesicles, Extracellular
D000071497	Immunogenicity, Vaccine	The capacity of VACCINES to stimulate the ADAPTIVE IMMUNE RESPONSE to produce antibodies and antigen-specific T-CELL responses. It is typically measured in vaccinated individuals in observational studies setting.	Antigenicity, Vaccine,Vaccine Antigenicity,Vaccine Immunogenicity
D000080943	Bacterial Outer Membrane	The outermost cell envelope of GRAM-NEGATIVE BACTERIA composed of PHOSPHOLIPIDS; LIPOPOLYSACCHARIDES (LPS), and BACTERIAL OUTER MEMBRANE PROTEINS. The bacterial outer membrane LPS demonstrates cytotoxicity (see LIPID A and BACTERIAL O ANTIGEN).	Bacterial Outer Membranes,Membrane, Bacterial Outer,Outer Membrane, Bacterial