Brucella abortus RB51 Induces Protection in Mice Orally Infected with the Virulent Strain B. abortus 2308

ABSTRACT Brucellae are gram-negative, facultative intracellular bacteria which are one of the most common causes of abortion in animals. In addition, they are the source of a severe zoonosis. In this trial, we evaluated the effect of oral inoculation of Brucella abortus RB51 in mice against a challenge infection with B. abortus 2308. First, we showed that a gastric acid neutralization prior to the oral inoculation contributed to a more homogeneous and consistent infection with both vaccine strain B. abortus RB51 and virulent strain B. abortus 2308. Successively, we assessed the clearance and the immune response following an oral infection with B. abortus RB51. Oral inoculation gave a mild infection which was cleared 42 days after infection, and it induced a delayed humoral and cell-mediated immune response. Finally, we immunized mice by oral inoculation with B. abortus RB51, and we challenged them with the virulent strain B. abortus 2308 by an oral or intraperitoneal route 42 days after vaccination. Oral inoculation of B. abortus RB51 was able to give protection to mice infected with the virulent strain B. abortus 2308 by the oral route but not to mice infected intraperitoneally. Our results indicate that oral inoculation of mice with B. abortus RB51 is able to give a protective immunity against an oral infection with virulent strains, and this protection seems to rely on an immune response at the mucosal level.

Download Full-text

Selection of Criteria for Assessing Protective Immunity at Different Times of Experimental Tularemia in a Mouse Model

Biotekhnologiya ◽

10.21519/0234-2758-2021-37-4-65-77 ◽

2021 ◽

Vol 37 (4) ◽

pp. 65-77

Author(s):

G.M. Titareva ◽

A.N. Mokrievich ◽

T.I. Kombarova ◽

G.M. Vakhrameeva ◽

R.I. Mironova ◽

...

Keyword(s):

Immune Response ◽

B Cells ◽

Vaccine Strain ◽

Protective Immunity ◽

T And B Cells ◽

Immunological Parameters ◽

Protective Properties ◽

Virulent Strains ◽

Ifn Γ

It is known that the body's defense against infection by the intracellular bacterium Francisella tularensis is provided by the activation of the cellular and humoral immune response. However, their role in long-term protection (25 years and more) against virulent strains of F. tularensis is not well understood. The identification of clear criteria for assessing protective immunity to the tularemia causative agent at different times after vaccination will make it possible to more efficiently develop new genetically determined vaccine strains. The goal of our research was to select and assess immunological parameters reflecting the protective properties of the vaccine strain F. tularensis 15 NIIEG and its derivatives, F. tularensis 15/23-1∆recA and F. tularensis 15/ 23-1/sodB∆recA, in the long term after immunization. To assess the functional activity of T and B cells, flow cytometry was used.The assessment of the production of cytokines IFN-γ, IL-4, IL-10, IL-17A and titers of specific class G immunoglobulins to F. tularensis lipopolysaccharide (LPS)in blood serum was performed by ELISA on days 30, 60, 90 and 180 after immunization. Evaluation of the protective properties of vaccine preparations in the above-mentioned terms was carried out after subcutaneous infection with test-infecting virulent strains, Schu and 503 of tularensis and holarctica subspecies, respectively. It was shown that vaccination with the studied strains in 100% of cases protected from infection with the strain 503 of the holarctica subspecies, analogous to the vaccine strain. When infected with a virulent Schu strain of the hetrologous tularensis subspecies, a decrease in the effectiveness of protection was observed starting from 60 days after immunization. Evaluation of immunological parameters showed that at all studied periods after immunization, IgG antibodies to F. tularensis LPS were detected in the blood sera of immunized mice. In vitro experiments on stimulation of immune response in spleen lymphocytes of vaccinated mice to the F. tularensis antigen showed a significant increase in the level of secreted IFN-γ, a slight increase in secreted IL-10 and an enhanced expression of the CD69 molecule on the surface of T and B cells. Thus, the level of IFN-γ and the expression of the CD69 molecule on the surface of T and B cells in response to restimulation of lymphocytes of immune animals with tularemia antigen can serve as criteria for immune protection in experimental tularemia in a mouse model at different times after vaccination. Key words: vaccine strain, Fransicella tularensis, immunogenicity, protection, memory T cells, IgG, cellular immunity Funding - The work was supported by the Branch Program of the Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing.

Download Full-text

Immune Response and Alveolar Bone Resorption in a Mouse Model of Treponema denticola Infection

Infection and Immunity ◽

10.1128/iai.01004-08 ◽

2008 ◽

Vol 77 (2) ◽

pp. 694-698 ◽

Cited By ~ 32

Author(s):

Song F. Lee ◽

Elisoa Andrian ◽

Elden Rowland ◽

Ignacio Christian Marquez

Keyword(s):

Immune Response ◽

Bone Resorption ◽

Alveolar Bone ◽

Interleukin 10 ◽

Oral Infection ◽

Infection Model ◽

Treponema Denticola ◽

Outer Sheath ◽

Oral Inoculation ◽

Animal Infection

ABSTRACT Treponema denticola is considered to be an agent strongly associated with periodontal disease. The lack of an animal infection model has hampered the understanding of T. denticola pathogenesis and the host's immune response to infection. In this study, we have established an oral infection model in mice, demonstrating that infection by oral inoculation is feasible. The presence of T. denticola in the oral cavities of the animals was confirmed by PCR. Mice given T. denticola developed a specific immune response to the bacterium. The antibodies generated from the infection were mainly of the immunoglobulin G1 subclass, indicating a Th2-tilted response. The antibodies recognized 11 T. denticola proteins, of which a 62-kDa and a 53-kDa protein were deemed immunodominant. The two proteins were identified, respectively, as dentilisin and the major outer sheath protein by mass spectrometry. Splenocytes cultured from the infected mice no longer produced interleukin-10 and produced markedly reduced levels of gamma interferon relative to those produced by naïve splenocytes upon stimulation with T. denticola. Mandibles of infected mice showed significantly greater bone resorption (P < 0.01) than those of mock-infected controls.

Download Full-text

Protective Immunity Elicited by a Divalent DNA Vaccine Encoding Both the L7/L12 and Omp16 Genes of Brucella abortus in BALB/c Mice

Infection and Immunity ◽

10.1128/iai.74.5.2734-2741.2006 ◽

2006 ◽

Vol 74 (5) ◽

pp. 2734-2741 ◽

Cited By ~ 68

Author(s):

Deyan Luo ◽

Bing Ni ◽

Peng Li ◽

Wei Shi ◽

Songle Zhang ◽

...

Keyword(s):

Immune Response ◽

Dna Vaccine ◽

Brucella Abortus ◽

Protective Efficacy ◽

Virulent Strain ◽

T Helper 1 ◽

Genetic Vaccine ◽

Cellular Immune

ABSTRACT This study was designed to evaluate the immunogenicity and the protective efficacy of a divalent fusion DNA vaccine encoding both the Brucella abortus L7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane lipoprotein), designated pcDNA3.1-L7/L12-Omp16. Intramuscular injection of this divalent DNA vaccine into BALB/c mice elicited markedly both humoral and cellular immune responses. The specific antibodies exhibited a dominance of immunoglobulin G2a (IgG2a) over IgG1. In addition, the dual-gene DNA vaccine elicited a strong T-cell proliferative response and induced a large amount of gamma interferon-producing T cells upon restimulation in vitro with recombinant fusion protein L7/L12-Omp16, suggesting the induction of a typical T-helper-1-dominated immune response in vivo. This divalent DNA vaccine could also induce a significant level of protection against challenge with the virulent strain B. abortus 544 in BALB/c mice. Furthermore, the protection level induced by the divalent DNA vaccine was significantly higher than that induced by the univalent DNA vaccines pcDNA3.1-L7/L12 or pcDNA3.1-Omp16. Taken together, the results of this study verify for the first time that the Omp16 gene can be a candidate target for a DNA vaccine against brucellosis. Additionally, a divalent genetic vaccine based on the L7/L12 and Omp16 genes can elicit a stronger cellular immune response and better immunoprotection than the relevant univalent vaccines can.

Download Full-text

Yersinia enterocolitica as a Vehicle for a Naked DNA Vaccine Encoding Brucella abortus Bacterioferritin or P39 Antigen

Infection and Immunity ◽

10.1128/iai.70.4.1915-1923.2002 ◽

2002 ◽

Vol 70 (4) ◽

pp. 1915-1923 ◽

Cited By ~ 35

Author(s):

Ayman Al-Mariri ◽

Anne Tibor ◽

Pascal Lestrate ◽

Pascal Mertens ◽

Xavier De Bolle ◽

...

Keyword(s):

Immune Response ◽

Yersinia Enterocolitica ◽

Dna Vaccine ◽

Brucella Abortus ◽

Protective Immunity ◽

Cell Mediated Immunity ◽

Naked Dna ◽

Serotype O ◽

Specific Serum

ABSTRACT Brucella is a facultative intracellular parasite that causes brucellosis in animals and humans. The protective immune response against Brucella involves both humoral and cell-mediated immunity. In previous studies, we demonstrated that the T-dominant Brucella antigens bacterioferritin (BFR) and P39 administered either as CpG adjuvant recombinant proteins or as naked-DNA plasmids induced a specific Th1-biased immune response in mice. In order to improve the protection conferred by the BFR and P39 vaccines and to evaluate the additive role of antilipopolysaccharide (anti-LPS) antibodies, we used live attenuated Yersinia enterocolitica serotypes O:3 and O:9 as delivery vectors for naked-DNA plasmids encoding these BFR and P39 antigens. Following two intragastric immunizations in BALB/c mice, the Yersinia vectors harboring a DNA vaccine encoding BFR or P39 induced antigen-specific serum immunoglobulin and Th1-type responses (both lymphocyte proliferation and gamma interferon production) among splenocytes. Moreover, as expected, antibodies recognizing Brucella abortus 544 lipopolysaccharide were detected in O:9-immunized mice but not in O:3-treated animals. Animals immunized with O:9 organisms carrying pCI or with O:9 organisms alone were found to be significantly resistant to infection by B. abortus 544. Our data demonstrated that pCI plasmids encoding BFR or P39 and delivered with live attenuated strains of Yersinia O:3 or O:9 can trigger Th1-type responses. The fact than only O:9 vectors induced a highly significant protective immunity against B. abortus 544 infection pointed out the crucial role of anti-LPS antibodies in protection. The best protection was conferred by a serotype O:9 strain carrying pCIP39, confirming the importance of the P39 T-cell antigen in this mechanism.

Download Full-text

Cell mediated immune response after challenge in Omp25 liposome immunized mice contributes to protection against virulent Brucella abortus 544

Vaccine ◽

10.1016/j.vaccine.2012.12.043 ◽

2013 ◽

Vol 31 (8) ◽

pp. 1231-1237 ◽

Cited By ~ 21

Author(s):

Divya Goel ◽

Vinoth Rajendran ◽

Prahlad C. Ghosh ◽

Rakesh Bhatnagar

Keyword(s):

Immune Response ◽

Brucella Abortus ◽

Cell Mediated Immune Response

Download Full-text

Vaccination with the major secretory protein of Legionella pneumophila induces cell-mediated and protective immunity in a guinea pig model of Legionnaires' disease.

Journal of Experimental Medicine ◽

10.1084/jem.169.3.691 ◽

1989 ◽

Vol 169 (3) ◽

pp. 691-705 ◽

Cited By ~ 51

Author(s):

S J Blander ◽

M A Horwitz

Keyword(s):

Immune Response ◽

Legionella Pneumophila ◽

Guinea Pigs ◽

Protective Immunity ◽

Secretory Protein ◽

Sublethal Dose ◽

Exact Test ◽

Cell Mediated Immune Response ◽

Legionnaires Disease ◽

Guinea Pig Model

We have examined the capacity of the major secretory protein (MSP) of Legionella pneumophila to induce humoral, cell-mediated, and protective immunity in a guinea pig model of Legionnaires' disease. MSP was purified to homogeneity by ammonium sulfate precipitation, molecular sieve chromatography, and ion-exchange chromatography. The purified MSP was nonlethal and nontoxic to guinea pigs upon subcutaneous administration. Guinea pigs immunized with a sublethal dose of aerosolized L. pneumophila or a subcutaneous dose of MSP developed a strong cell-mediated immune response to MSP. Such guinea pigs exhibited marked splenic lymphocyte proliferation and cutaneous delayed-type hypersensitivity to MSP in comparison with control animals. Guinea pigs immunized with MSP also developed a strong humoral immune response to MSP, as assayed by an ELISA. The median reciprocal antibody titer was 362 (range 45 to greater than 2,048) for immunized animals compared with less than 8 for controls. In contrast, guinea pigs immunized with a sublethal dose of L. pneumophila failed to develop anti-MSP antibody. Guinea pigs immunized with MSP and then challenged with a lethal aerosol dose of L. pneumophila exhibited highly significant protective immunity in each of five consecutive experiments. MSP induced protective immunity in dose-dependent fashion (40 greater than 10 greater than 2.5 greater than 0.6 micrograms MSP); vaccination with two doses of as little as 2.5 micrograms MSP induced significant protective immunity (p = 0.01, Fisher's Exact Test, two-tailed). Altogether, 21 (81%) of 26 animals immunized with 40 micrograms MSP survived challenge compared with 0 (0%) of 26 sham-immunized control animals (p = 7 x 10(-10), Fisher's Exact Test, two-tailed). MSP-immunized but not control guinea pigs were able to limit L. pneumophila multiplication in their lungs. This study demonstrates that (a) guinea pigs sublethally infected with L. pneumophila develop a strong cell-mediated immune response to MSP; (b) guinea pigs immunized with MSP develop a strong humoral and cell-mediated immune response to MSP; (c) guinea pigs immunized with MSP develop a very high level of protective immunity to lethal aerosol challenge with L. pneumophila; and (d) MSP-immunized animals are able to limit L. pneumophila multiplication in their lungs. MSP, an extracellular protein of an intracellular pathogen, has potential as a vaccine for the prevention of Legionnaires' disease. Secretory molecules of other intracellular pathogens may also have vaccine potential.

Download Full-text