Genetic stability of Brucella abortus S19 and RB51 vaccine strains by multiple locus variable number tandem repeat analysis (MLVA16)

Dorneles, Elaine Maria Seles; Faria, Ana Paula Paiva de; Pauletti, Rebeca Barbosa; Santana, Jordana Almeida; Caldeira, George Afonso Vítor; Heinemann, Marcos Bryan; Titze‐de‐Almeida, Ricardo; Lage, Andrey Pereira

doi:10.1016/j.vaccine.2013.07.063

Cited by 16 publications

(11 citation statements)

References 15 publications

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“…CD4 + and CD8 + T cells are considered to be the primary source of these protective cytokines during Brucella infections [8][9][10]. The importance of the T cell subsets varies by the route of immunization and the vaccine components [11][12][13][14][15][16][17][18]. Recent reports showed that mucosal exposure to this pathogen stimulates IFN-γ-producing CD8 + T cells for protection against brucellosis, not by their cytotoxic function [19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Targeting resident memory T cell immunity culminates in pulmonary and systemic protection against Brucella infection

et al. 2020

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Brucellosis remains the most common zoonotic disease globally. Currently no vaccines for humans exist, and conventional brucellosis vaccines for livestock fail to confer complete protection; hence, an improved vaccine is needed. Although Brucella infections primarily occur following a mucosal exposure, vaccines are administered parenterally. Few studies have considered mucosal vaccinations, or even targeting of tissue-resident memory T (T RM) cells. T RM cells protect against viral infections, but less is known of their role in bacterial infections, and even less for brucellosis. Oral prime, nasal boost with a newly developed Brucella abortus double mutant (znBAZ) confers nearly complete protection against pulmonary challenge with wild-type (wt) B. abortus 2308, and its protective efficacy is >2800-fold better than the RB51 vaccine. Vaccination with znBAZ potently stimulated CD8 + T cells, whereas mucosal vaccination with RB51 induced mostly CD4 + T cells. Subsequent analysis revealed these pulmonary CD44 + CD69 + CD8 + T cells to be either CD103 + or CD103-T RM cells, and these sequestered to the lung parenchyma as CXCR3 lo and to the airways as CXCR3 hi. Both CD8 + T RM subsets contained single-positive IFN-γ and TNF-α, as well as, polyfunctional cells. IL-17-producing CD8 + T RM cells were also induced by znBAZ vaccination, but in vivo IL-17 neutralization had no impact upon protection. In vivo depletion of CD4 + T cells had no impact upon protection in znBAZ-vaccinated mice. In contrast, CD4 + T cell depletion reduced RB51's protective efficacy in spleens and lungs by two-and three-logs, respectively. Although anti-CD8 mAb-treated znBAZ-vaccinated mice showed a significantly reduced pulmonary efficacy, this treatment failed to completely deplete the lung CD8 + T cells, leaving the CD103 + and CD103-CD8 + T RM cell ratios intact. Only znBAZ-vaccinated CD8-/mice were fully sensitive to pulmonary challenge with virulent wt B. abortus 2308 since CD8 + T RM cells could not be induced. Collectively, these data demonstrate the key role of mucosal vaccination for the generation of CD8 + T RM cells in protecting against pulmonary challenge with virulent B. abortus.

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Section: Introductionmentioning

confidence: 99%

Targeting resident memory T cell immunity culminates in pulmonary and systemic protection against Brucella infection

et al. 2020

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“…Comparison of the results observed in the eight conserved loci included in panel 1 by Le Flèche et al [6] with those available in the MLVA bank 2014 (http://mlva.u-psud.fr/brucella/) showed genotypes 27, 40 and 28 for the strains classified as MLVA16 genotypes RB, W and Z, respectively. Genotype RB was identical to the previously describe [6,16] for RB51 vaccine strain. The MLVA16 pattern for genotypes W and Z did not find correspondence with those deposited on MLVA bank 2014.…”

Section: Resultsmentioning

confidence: 99%

“…Futhermore, the examination of in vitro stability of the B. abortus RB51 vaccine strain, B. abortus strain 2308 and B. abortus field isolates by serial passages in culture medium showed no change in MLVA16 profile [9,16]. Likewise, the analysis of B. abortus S19 vaccine strain from different batches of different manufacturers did not reveal significant differences in MLVA16 pattern [17].…”

Section: Discussionmentioning

confidence: 99%

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Genetic stability of Brucella abortus isolates from an outbreak by multiple-locus variable-number tandem repeat analysis (MLVA16)

et al. 2014

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BackgroundBrucellosis caused by Brucella abortus is one of the most important zoonoses in the world. Multiple-locus variable-number tandem repeat analysis (MLVA16) has been shown be a useful tool to epidemiological traceback studies in B. abortus infection. Thus, the present study aimed (i) to evaluate the genetic diversity of B. abortus isolates from a brucellosis outbreak, and (ii) to investigate the in vivo stability of the MLVA16 markers.ResultsThree-hundred and seventy-five clinical samples, including 275 vaginal swabs and 100 milk samples, were cultured from a brucellosis outbreak in a cattle herd, which adopted RB51 vaccination and test-and-slaughter policies. Thirty-seven B. abortus isolates were obtained, eight from milk and twenty-nine from post-partum/abortion vaginal swabs, which were submitted to biotyping and genotyping by MLVA16. Twelve B. abortus isolates obtained from vaginal swabs were identified as RB51. Twenty four isolates, seven obtained from milk samples and seventeen from vaginal swabs, were identified as B. abortus biovar 3, while one isolate from vaginal swabs was identified as B. abortus biovar 1. Three distinct genotypes were observed during the brucellosis outbreak: RB observed in all isolates identified as RB51; W observed in all B. abortus biovar 3 isolates; and Z observed in the single B. abortus biovar 1 isolate. Epidemiological and molecular data show that the B. abortus biovar 1 genotype Z strain is not related to the B. abortus biovar 3 genotype W isolates, and represents a new introduction B. abortus during the outbreak.ConclusionsThe results of the present study on typing of multiple clinical B. abortus isolates from the same outbreak over a sixteen month period indicate the in vivo stability of MLVA16 markers, a low genetic diversity among B. abortus isolates and the usefulness of MLVA16 for epidemiological studies of bovine brucellosis.

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“…vaccines is usually based on in vitro criteria, including physico-chemical and microbiological tests as purity, dissociation, determination of pH, humidity and count of viable bacteria. Nevertheless, genetic stability has recently been proposed as an additional criterion in assessing the quality of B. abortus vaccines [40,41]. Immunogenicity test performed in mouse is another alternative to assess the quality of bovine brucellosis vaccines, however as RB51 does not have cutoff points, i.e.…”

Section: Bovine Brucellosis Control and Eradication Programsmentioning

confidence: 99%

Brucella Abortus Vaccines: Use in Control Programs and Immune Response

Lage¹

2017

J Bacteriol Mycol

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Brucella spp. is a highly infectious pathogen that affects numerous livestock and wild animal species besides humans, and that although eradicated in some countries, remains one of the most economically important zoonosis worldwide. Strain 19 and RB51 are the two Brucella abortus vaccine strains more largely used in the control of brucellosis in cattle worldwide, being effective in the prevention of abortion and infection, besides offering long lasting protection. Here, we reviewed the main aspects of the B. abortus vaccines and their use in brucellosis control and eradication programs over the years and the current understanding in the immune response triggered by these two B. abortus vaccines, especially in cattle.

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Genetic stability of Brucella abortus S19 and RB51 vaccine strains by multiple locus variable number tandem repeat analysis (MLVA16)

Cited by 16 publications

References 15 publications

Targeting resident memory T cell immunity culminates in pulmonary and systemic protection against Brucella infection

Targeting resident memory T cell immunity culminates in pulmonary and systemic protection against Brucella infection

Genetic stability of Brucella abortus isolates from an outbreak by multiple-locus variable-number tandem repeat analysis (MLVA16)

Brucella Abortus Vaccines: Use in Control Programs and Immune Response

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