Induction of a Specific Strong Polyantigenic Cellular Immune Response after Short-Term Chemotherapy Controls Bacillary Reactivation in Murine and Guinea Pig Experimental Models of Tuberculosis

Guirado, Evelyn; Gil, Olga; Cáceres, Neus; Singh, Mahavir; Vilaplana, Cristina; Cardona, Père-Joan

doi:10.1128/cvi.00094-08

Cited by 36 publications

(39 citation statements)

References 35 publications

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“…However, Guirado et al showed that vaccination of mice with fragments of M. tuberculosis incorporated into liposomes were effective at potentiating chemotherapy [23]. In the Dhillon study, the authors attributed the species-specific differences in drug treatment responses to host immunity, which they characterized as “mainly bacteriostatic in mice and bactericidal in guinea pigs”.…”

Section: Introductionmentioning

confidence: 99%

Drug treatment combined with BCG vaccination reduces disease reactivation in guinea pigs infected with Mycobacterium tuberculosis

Shang

Shanley

Caraway

et al. 2012

Vaccine

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Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease.

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Section: Introductionmentioning

confidence: 99%

Drug treatment combined with BCG vaccination reduces disease reactivation in guinea pigs infected with Mycobacterium tuberculosis

Shang

Shanley

Caraway

et al. 2012

Vaccine

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“…In the present study, IP-infected mice were used. The results from experiments using the aerosol-infected mouse model couldn't demonstrate a high level of response to structural M. tuberculosis antigens as clearly as do the results from this IP experiment (4).…”

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confidence: 55%

“…RUTI has already demonstrated a protective effect in a low-dose aerosol model, inducing a large and fast immune response against antigens secreted by actively growing Mycobacterium tuberculosis bacilli (2,4). Given the long period required to test this therapeutic approach using the aerosol model, the IP model could be a reliable one to test new immunotherapeutic candidates.…”

mentioning

confidence: 99%

Enhanced Gamma Interferon Responses of Mouse Spleen Cells following Immunotherapy for Tuberculosis Relapse

Gil

Vilaplana

Guirado

et al. 2008

Clin Vaccine Immunol

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Gamma interferon responses of spleen cells in mice were examined during postchemotherapy relapse of intraperitoneally induced latent tuberculous infection. The mycobacterial extract RUTI, which prevented the relapse, significantly enhanced the immune responses to secreted and structural recombinant mycobacterial antigens, suggesting that RUTI-mediated protection was mediated by activated T cells.The aim of this study was to assess the mechanisms of the vaccine RUTI as an adjunct to chemotherapy, in a latent tuberculosis experimental model based on the intraperitoneal (IP) infection of mice (6).RUTI has already demonstrated a protective effect in a low-dose aerosol model, inducing a large and fast immune response against antigens secreted by actively growing Mycobacterium tuberculosis bacilli (2, 4). Given the long period required to test this therapeutic approach using the aerosol model, the IP model could be a reliable one to test new immunotherapeutic candidates.Specific-pathogen-free, 7-week-old C57BL/6 female mice were treated by using procedures approved and supervised by the Animal Care Committee of the Germans Trias i Pujol University Hospital. M. tuberculosis strain H37Rv Pasteur was grown in Proskauer Beck medium containing 0.01% Tween 80 (9) to mid-log phase and stored at Ϫ70°C in 2-ml aliquots. Mice were vaccinated subcutaneously twice, at weeks 9 and 11, with RUTI, which consists of liposome-based detoxified fragments of M. tuberculosis cells, cultured under stress conditions and under good manufacturing procedure quality control by Archivel Farma (Badalona, Catalonia, Spain) (2).Mice were infected with 1 ϫ 10 5 CFU M. tuberculosis by IP injection and divided into three groups: the control group, infected but not treated; the chemotherapy-treated group (receiving 25 mg/kg of body weight isoniazid plus 10 mg/kg rifapentin once a week from week 3 to week 9 postinfection); and the vaccinated group, which received two RUTI inoculations after the chemotherapy, at weeks 9 and 11 after infection.The animals were euthanized with an overdose of isofluorane at week 13 postinfection, and the spleens were harvested. Viable bacteria (CFU) were counted four weeks after the spleen homogenates were plated on 7H11 Middlebrook agar (Biomedics s.l., Madrid, Spain) and incubated at 37°C. Data were recorded as the log 10 of the mean number of bacteria recovered per organ. The antigen-stimulated numbers of gamma interferon (IFN-␥)-secreting cells (in spot forming units [SFU] per 1 · 10 6 splenocytes; enzyme-linked immunospot assay [ELISPOT]) and levels of IFN-␥ production (in pg/ml; enzyme-linked immunosorbent assay [ELISA]) were determined after the splenocytes were stimulated for 18 and 96 h with 15 different recombinant antigens, purified protein derivative (10g/ml), or Mycobacterium bovis BCG (10 6 CFU), both purchased at SSI, Denmark. The M. tuberculosis antigens, comprising ESAT-6 (Rv3875), CFP-10 (Rv3874), MPT64 (Rv1980c), Ag 85B (Rv1886c), Ag 16kDa (Rv2031c), Ag 19kDa(Rv3763), Ag 38kDa (Rv0934), Ag 40kDa (Rv2780)...

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“…Significant protection was demonstrated in the mice sera treated with RUTI regimen in SCID mice [71]. The RUTI vaccine has shown prophylactic effect as therapeutic vaccine against tuberculosis.…”

Section: Current Therapeutic Tb Vaccines and Their Developmentsmentioning

confidence: 99%

Vaccines for TB: Lessons from the Past Translating into Future Potentials

Tye

Lew

Choong

et al. 2015

Journal of Immunology Research

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Development of vaccines for infectious diseases has come a long way with recent advancements in adjuvant developments and discovery of new antigens that are capable of eliciting strong immunological responses for sterile eradication of disease. Tuberculosis (TB) that kills nearly 2 million of the population every year is also one of the highlights of the recent developments. The availability or not of diagnostic methods for infection has implications for the control of the disease by the health systems but is not related to the immune surveillance, a phenomenon derived from the interaction between the bacteria and their host. Here, we will review the immunology of TB and current vaccine candidates for TB. Current strategies of developing new vaccines against TB will also be reviewed in order to further discuss new insights into immunotherapeutic approaches involving adjuvant and antigens combinations that might be of potential for the control of TB.

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Induction of a Specific Strong Polyantigenic Cellular Immune Response after Short-Term Chemotherapy Controls Bacillary Reactivation in Murine and Guinea Pig Experimental Models of Tuberculosis

Cited by 36 publications

References 35 publications

Drug treatment combined with BCG vaccination reduces disease reactivation in guinea pigs infected with Mycobacterium tuberculosis

Drug treatment combined with BCG vaccination reduces disease reactivation in guinea pigs infected with Mycobacterium tuberculosis

Enhanced Gamma Interferon Responses of Mouse Spleen Cells following Immunotherapy for Tuberculosis Relapse

Vaccines for TB: Lessons from the Past Translating into Future Potentials

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