lipid-a has been researched along with Tuberculosis--Pulmonary* in 6 studies
1 review(s) available for lipid-a and Tuberculosis--Pulmonary
Article | Year |
---|---|
Immunocorrelates of CAF family adjuvants.
The development of the CAF family adjuvant was initiated around 20 years ago when Statens Serum Institut was preparing its first generation protein based recombinant subunit vaccine against tuberculosis for clinical testing, but realized that there were no clinically relevant adjuvants available that would support the strong CMI response needed. Since then the aim for the adjuvant research at Statens Serum Institut has been to provide adjuvants with distinct immunogenicity profiles correlating with protection for any given infectious disease. Two of the adjuvants CAF01 and CAF09 are currently being evaluated in human clinical trials. The purpose of this review is to give an overview of the immunocorrelates of those CAF adjuvants furthest in development. We further aim at giving an overview of the mechanism of action of the CAF adjuvants. Topics: Adjuvants, Immunologic; Animals; Glycolipids; Humans; Immunity, Cellular; Immunity, Humoral; Immunogenicity, Vaccine; Lipid A; Liposomes; Mice; Quaternary Ammonium Compounds; Th1 Cells; Th17 Cells; Th2 Cells; Tuberculosis Vaccines; Tuberculosis, Pulmonary | 2018 |
1 trial(s) available for lipid-a and Tuberculosis--Pulmonary
Article | Year |
---|---|
Safety and immunogenicity of the adjunct therapeutic vaccine ID93 + GLA-SE in adults who have completed treatment for tuberculosis: a randomised, double-blind, placebo-controlled, phase 2a trial.
A therapeutic vaccine that prevents recurrent tuberculosis would be a major advance in the development of shorter treatment regimens. We aimed to assess the safety and immunogenicity of the ID93 + GLA-SE vaccine at various doses and injection schedules in patients with previously treated tuberculosis.. This randomised, double-blind, placebo-controlled, phase 2a trial was conducted at three clinical sites near Cape Town, South Africa. Patients were recruited at local clinics after receiving 4 months of tuberculosis treatment, and screened for eligibility after providing written informed consent. Participants were aged 18-60 years, BCG-vaccinated, HIV-uninfected, and diagnosed with drug-sensitive pulmonary tuberculosis. Eligible patients had completed standard treatment for pulmonary tuberculosis in the past 28 days. Participants were enrolled after completing standard treatment and randomly assigned sequentially to receive vaccine or placebo in three cohorts: 2 μg intramuscular ID93 + 2 μg GLA-SE on days 0 and 56 (cohort 1); 10 μg ID93 + 2 μg GLA-SE on days 0 and 56 (cohort 2); 2 μg ID93 + 5 μg GLA-SE on days 0 and 56 and placebo on day 28 (cohort 3); 2 μg ID93 + 5 μg GLA-SE on days 0, 28, and 56 (cohort 3); or placebo on days 0 and 56 (cohorts 1 and 2), with the placebo group for cohort 3 receiving an additional injection on day 28. Randomisation was in a ratio of 3:1 for ID93 + GLA-SE and saline placebo in cohorts 1 and 2, and in a ratio of 3:3:1 for (2 ×) ID93 + GLA-SE, (3 ×) ID93 + GLA-SE, and placebo in cohort 3. The primary outcomes were safety and immunogenicity (vaccine-specific antibody response and T-cell response). For the safety outcome, participants were observed for 30 min after each injection, injection site reactions and systemic adverse events were monitored until day 84, and serious adverse events and adverse events of special interest were monitored for 6 months after the last injection. Vaccine-specific antibody responses were measured by serum ELISA, and T-cell responses after stimulation with vaccine antigens were measured in cryopreserved peripheral blood mononuclear cells specimens using intracellular cytokine staining followed by flow cytometry. This study is registered with ClinicalTrials.gov, number NCT02465216.. Between June 17, 2015, and May 30, 2016, we assessed 177 patients for inclusion. 61 eligible patients were randomly assigned to receive: saline placebo (n=5) or (2 ×) 2 μg ID93 + 2 μg GLA-SE (n=15) on days 0 and 56 (cohort 1); saline placebo (n=2) or (2 ×) 10 μg ID93 + 2 μg GLA-SE (n=5) on days 0 and 56 (cohort 2); saline placebo (n=5) on days 0, 28 and 56, or 2 μg ID93 + 5 μg GLA-SE (n=15) on days 0 and 56 and placebo injection on day 28, or (3 ×) 2 μg ID93 + 5 μg GLA-SE (n=14) on days 0, 28, and 56 (cohort 3). ID93 + GLA-SE induced robust and durable antibody responses and specific, polyfunctional CD4 T-cell responses to vaccine antigens. Two injections of the 2 μg ID93 + 5 μg GLA-SE dose induced antigen-specific IgG and CD4 T-cell responses that were significantly higher than those with placebo and persisted for the 6-month study duration. Mild to moderate injection site pain was reported after vaccination across all dose combinations, and induration and erythema in patients given 2 μg ID93 + 5 μg GLA-SE in two or three doses. One participant had grade 3 erythema and induration at the injection site. No vaccine-related serious adverse events were observed.. Vaccination with ID93 + GLA-SE was safe and immunogenic for all tested regimens. These data support further evaluation of ID93 + GLA-SE in therapeutic vaccination strategies to improve tuberculosis treatment outcomes.. Wellcome Trust (102028/Z/13/Z). Topics: Adjuvants, Immunologic; Adolescent; Adult; Antibodies, Bacterial; Antitubercular Agents; Dose-Response Relationship, Immunologic; Double-Blind Method; Female; Glucosides; Humans; Immunogenicity, Vaccine; Lipid A; Male; Middle Aged; Mycobacterium tuberculosis; Recurrence; Secondary Prevention; Tuberculosis Vaccines; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Young Adult | 2021 |
4 other study(ies) available for lipid-a and Tuberculosis--Pulmonary
Article | Year |
---|---|
Combinational PRR Agonists in Liposomal Adjuvant Enhances Immunogenicity and Protective Efficacy in a Tuberculosis Subunit Vaccine.
Topics: Adjuvants, Immunologic; Animals; CD4-Positive T-Lymphocytes; Cytokines; Disease Models, Animal; Drug Compounding; Female; Glycolipids; Host-Pathogen Interactions; Immunogenicity, Vaccine; Lipid A; Liposomes; Lung; Mice, Inbred C57BL; Mycobacterium tuberculosis; Quaternary Ammonium Compounds; Receptors, Pattern Recognition; Time Factors; Tuberculosis Vaccines; Tuberculosis, Pulmonary; Vaccination; Vaccines, Subunit; Virulence | 2020 |
The importance of adjuvant formulation in the development of a tuberculosis vaccine.
An effective protein-based vaccine for tuberculosis will require a safe and effective adjuvant. There are few adjuvants in approved human vaccines, including alum and the oil-in-water-based emulsions MF59 (Novartis Vaccines and Diagnostics), AS03 and AS04 (GlaxoSmithKline Biologics), AF03 (Sanofi), and liposomes (Crucell). When used with pure, defined proteins, both alum and emulsion adjuvants are effective at inducing primarily humoral responses. One of the newest adjuvants in approved products is AS04, which combines monophosphoryl lipid A, a TLR-4 agonist, with alum. In this study, we compared two adjuvants: a stable oil-in-water emulsion (SE) and a stable oil-in-water emulsion incorporating glucopyranosyl lipid adjuvant, a synthetic TLR-4 agonist (GLA-SE), each together with a recombinant protein, ID93. Both the emulsion SE and GLA-SE adjuvants induce potent cellular responses in combination with ID93 in mice. ID93/SE induced Th2-biased immune responses, whereas ID93/GLA-SE induced multifunctional CD4(+) Th1 cell responses (IFN-γ, TNF-α, and IL-2). The ID93/GLA-SE vaccine candidate induced significant protection in mice and guinea pigs, whereas no protection was observed with ID93/SE, as assessed by reductions in bacterial burden, survival, and pathology. These results highlight the importance of properly formulating subunit vaccines with effective adjuvants for use against tuberculosis. Topics: Adjuvants, Immunologic; Animals; Emulsions; Female; Guinea Pigs; Lipid A; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Survival Analysis; Th1 Cells; Th2 Cells; Tuberculosis Vaccines; Tuberculosis, Pulmonary; Vaccines, Subunit | 2012 |
Oral vaccination with subunit vaccines protects animals against aerosol infection with Mycobacterium tuberculosis.
Immunity against Mycobacterium tuberculosis depends largely on activation of cell-mediated responses, and gamma interferon has been shown to play a crucial role in this process in both humans and animal models. Since the lung is normally the organ in which infection is initiated and is the major site of pathology, immune responses in the lung play a significant role in restricting initial infection with M. tuberculosis. The aim of the present study was to stimulate efficient immunity in the lung by targeting the gut mucosa. Detoxified monophosphoryl lipid A (MPL) has been shown to be a relatively nontoxic adjuvant which efficiently promotes the induction of type 1 responses when it is given by the traditional subcutaneous route. We have therefore compared subcutaneous immunization of mice to oral immunization by using a model subunit vaccine carrying two immunodominant proteins from M. tuberculosis, in combination with MPL-based adjuvants. While less effective when used to prime a response, a heterologous priming and boosting vaccination strategy employing oral boosting induced significant systemic type 1 responses which equaled and surpassed those attained by subcutaneous immunization protocols. Moreover, the increased immune responses observed correlated with the induction of substantial protection against subsequent aerosol infection with virulent M. tuberculosis at levels comparable to, or better than, those obtained by multiple subcutaneous vaccinations. These results demonstrate that booster vaccinations via mucosal surfaces, by combining efficient subunit vaccines with the potent adjuvant MPL, may be an effective method of addressing some of the shortcomings of current vaccination strategies. Topics: Acyltransferases; Adjuvants, Immunologic; Administration, Oral; Aerosols; Animals; Antigens, Bacterial; Bacterial Proteins; Bacterial Toxins; BCG Vaccine; Cholera Toxin; Disease Models, Animal; Enterotoxins; Escherichia coli Proteins; Female; Guinea Pigs; Immunization, Secondary; Injections, Subcutaneous; Lipid A; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Recombinant Fusion Proteins; Tuberculosis, Pulmonary; Vaccination; Vaccines, Synthetic | 2002 |
Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis.
The results of this study provide the first evidence that two completely separate vaccine approaches, one based on a subunit vaccine consisting of a mild adjuvant admixed with purified culture filtrate proteins and enhanced by the cytokine interleukin-2 and the second based on immunization with DNA encoding the Ag85A protein secreted by Mycobacterium tuberculosis, could both prevent the onset of caseating disease, which is the hallmark of the guinea pig aerogenic infection model. In both cases, however, the survival of vaccinated guinea pigs was shorter than that conferred by Mycobacterium bovis BCG, with observed mortality of these animals probably due to consolidation of lung tissues by lymphocytic granulomas. An additional characteristic of these approaches was that neither induced skin test reactivity to commercial tuberculin. These data thus provide optimism that development of nonliving vaccines which can generate long-lived immunity approaching that conferred by the BCG vaccine is a feasible goal. Topics: Acyltransferases; Animals; Antigens, Bacterial; Bacterial Proteins; BCG Vaccine; Disease Models, Animal; Evaluation Studies as Topic; Female; Guinea Pigs; Hypersensitivity, Delayed; Interleukin-2; Lipid A; Lung; Mice; Tuberculosis, Pulmonary; Vaccination; Vaccines, DNA | 1998 |