Cationic pH-sensitive liposome-based subunit tuberculosis vaccine induces protection in mice challenged with Mycobacterium tuberculosis
European Journal of Pharmaceutics and Biopharmaceutics, vol. 203, pp. 114437
Abstract
Tuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current vaccine, BCG, has insufficient impact. In this article, a novel subunit vaccine against TB was developed, using the Ag85B-ESAT6-Rv2034 fusion antigen, two adjuvants – CpG and MPLA, and a cationic pH-sensitive liposome as a delivery system, representing a new TB vaccine delivery strategy not previously reported for TB. In vitro in human dendritic cells (DCs), the adjuvanted formulation induced a significant increase in the production of (innate) cytokines and chemokines compared to the liposome without additional adjuvants. In vivo, the new vaccine administrated subcutaneously significantly reduced Mycobacterium tuberculosis (Mtb) bacterial load in the lungs and spleens of mice, significantly outperforming results from mice vaccinated with the antigen mixed with adjuvants without liposomes. In-depth analysis underpinned the vaccine’s effectiveness in terms of its capacity to induce polyfunctional CD4+ and CD8+ T-cell responses, both considered essential for controlling Mtb infection. Also noteworthy was the differential abundance of various CD69+ B-cell subpopulations, which included IL17-A-producing B cells. The vaccine stimulated robust antigen-specific antibody titers, further extending its potential as a novel protective agent against TB.
Authors 8
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center (LUMC), the Netherlands. Electronic address: m.m.szachniewicz@lumc.nl
Department of Infectious Diseases, Leiden University Medical Center (LUMC), The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center (LUMC), the Netherlands
Department of Infectious Diseases, Leiden University Medical Center (LUMC), The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center (LUMC), the Netherlands
Department of Infectious Diseases, Leiden University Medical Center (LUMC), The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center (LUMC), the Netherlands
Department of Infectious Diseases, Leiden University Medical Center (LUMC), The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center (LUMC), the Netherlands
Department of Infectious Diseases, Leiden University Medical Center (LUMC), The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center (LUMC), the Netherlands
Department of Infectious Diseases, Leiden University Medical Center (LUMC), The Netherlands
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Affiliation as printed
Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, the Netherlands
Division of BioTherapeutics, Leiden Academic Centre for Drug Research (LACDR), Leiden University, The Netherlands
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Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Center for Infectious Diseases, Leiden University Medical Center (LUMC), the Netherlands
Department of Infectious Diseases, Leiden University Medical Center (LUMC), The Netherlands
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