Intravenous Bacille Calmette–Guérin vaccination protects simian immunodeficiency virus-infected macaques from tuberculosis

Larson, Erica C.; Ellis-Connell, Amy L.; Rodgers, Mark A.; Gubernat, Abigail K.; Gleim, Janelle L.; Moriarty, Ryan V.; Balgeman, Alexis J.; Ameel, Cassaundra L.; Jauro, Solomon; Tomko, Jaime A.; Kracinovsky, Kara B.; Maiello, Pauline; Borish, H. Jake; White, Alexander G.; Klein, Edwin; Bucsan, Allison N.; Darrah, Patricia A.; Seder, Robert A.; Roederer, Mario; Lin, Philana Ling; Flynn, JoAnne L.; O’Connor, Shelby L.; Scanga, Charles A.

doi:10.1038/s41564-023-01503-x

Cited by 19 publications

(8 citation statements)

References 64 publications

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“…A crucial challenge is the induction of a respiratory immune response that will control inhalational anthrax. A recent report using BCG [ 127 , 128 ] raises the interesting concept that an immune response generated from within the lung capillaries could trigger a more effective protective immunity than from the aerial space. B. anthracis could be a valid candidate for such exploration.…”

Section: Some Points Of Discussionmentioning

confidence: 99%

Bacillus anthracis, “la maladie du charbon”, Toxins, and Institut Pasteur

Goossens

2024

Toxins

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Institut Pasteur and Bacillus anthracis have enjoyed a relationship lasting almost 120 years, starting from its foundation and the pioneering work of Louis Pasteur in the nascent fields of microbiology and vaccination, and blooming after 1986 following the molecular biology/genetic revolution. This contribution will give a historical overview of these two research eras, taking advantage of the archives conserved at Institut Pasteur. The first era mainly focused on the production, characterisation, surveillance and improvement of veterinary anthrax vaccines; the concepts and technologies with which to reach a deep understanding of this research field were not yet available. The second period saw a new era of B. anthracis research at Institut Pasteur, with the anthrax laboratory developing a multi-disciplinary approach, ranging from structural analysis, biochemistry, genetic expression, and regulation to bacterial-host cell interactions, in vivo pathogenicity, and therapy development; this led to the comprehensive unravelling of many facets of this toxi-infection. B. anthracis may exemplify some general points on how science is performed in a given society at a given time and how a scientific research domain evolves. A striking illustration can be seen in the additive layers of regulations that were implemented from the beginning of the 21st century and their impact on B. anthracis research. B. anthracis and anthrax are complex systems that raise many valuable questions regarding basic research. One may hope that B. anthracis research will be re-initiated under favourable circumstances later at Institut Pasteur.

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Section: Some Points Of Discussionmentioning

confidence: 99%

Bacillus anthracis, “la maladie du charbon”, Toxins, and Institut Pasteur

Goossens

2024

Toxins

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“…This study and one other BCG IV study (Larson et al, 2023) were performed in Mauritian cynomolgus macaques (MCM) while our original study was performed in rhesus macaques. MCM have similar susceptibility to TB disease as rhesus macaques (Maiello et al, 2018;Rodgers et al, 2018) and BCG IV provides robust protection in both macaque species (Darrah et al, 2020;Larson et al, 2023). In contrast, BCG-TetOFF-DL or WT BCG delivered IV provided only modest protection in mice in the current study, similar to other studies with IV BCG in mice (Pym et al, 2003;Mittrücker et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Control animals (unvaccinated) were challenged at the same time. Historical control unvaccinated and Mtb challenged MCMs (previously published by our group (Larson et al ., 2023)) were included for statistical analyses and comparison.…”

Section: Methodsmentioning

confidence: 99%

A “suicide” BCG strain provides enhanced immunogenicity and robust protection againstMycobacterium tuberculosisin macaques

Smith,

Su,

Wallach

et al. 2023

Preprint

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Intravenous (IV) BCG delivery provides robust protection againstMycobacterium tuberculosis(Mtb) in macaques but poses safety challenges. Here, we constructed two BCG strains (BCG-TetON-DL and BCG-TetOFF-DL) in which tetracyclines regulate two phage lysin operons. Once the lysins are expressed, these strains are cleared in immunocompetent and immunocompromised mice, yet induced similar immune responses and provided similar protection against Mtb challenge as wild type BCG. Lysin induction resulted in release of intracellular BCG antigens and enhanced cytokine production by macrophages. In macaques, cessation of doxycycline administration resulted in rapid elimination of BCG-TetOFF-DL. However, IV BCG-TetOFF-DL induced increased pulmonary CD4 T cell responses compared to WT BCG and provided robust protection against Mtb challenge, with sterilizing immunity in 6 of 8 macaques, compared to 2 of 8 macaques immunized with WT BCG. Thus, a “suicide” BCG strain provides an additional measure of safety when delivered intravenously and robust protection against Mtb infection.

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“…A higher proportion of mycobacteria-specific T-cells in airways, tissue-resident memory T-cells, and robust immunoglobulin IgM responses were identified as correlates of protection in macaques immunized intravenously with BCG 13 , 198 . Intravenous BCG immunization also protected simian immunodeficiency virus (SIV)-infected macaques from M. tuberculosis infection 199 . These studies demonstrate that BCG administration via the intravenous route is more immunogenic and efficacious than the conventional intradermally administered BCG.…”

Section: Tb Vaccine Preclinical Evaluation Modelsmentioning

confidence: 99%

Antigen identification strategies and preclinical evaluation models for advancing tuberculosis vaccine development

Chugh,

Bahal,

Dhiman

et al. 2024

npj Vaccines

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In its myriad devastating forms, Tuberculosis (TB) has existed for centuries, and humanity is still affected by it. Mycobacterium tuberculosis (M. tuberculosis), the causative agent of TB, was the foremost killer among infectious agents until the COVID-19 pandemic. One of the key healthcare strategies available to reduce the risk of TB is immunization with bacilli Calmette-Guerin (BCG). Although BCG has been widely used to protect against TB, reports show that BCG confers highly variable efficacy (0-80%) against adult pulmonary TB. Unwavering efforts have been made over the past 20 years to develop and evaluate new TB vaccine candidates. The failure of conventional preclinical animal models to fully recapitulate human response to TB, as also seen for the failure of MVA85A in clinical trials, signifies the need to develop better preclinical models for TB vaccine evaluation. In the present review article, we outline various approaches used to identify protective mycobacterial antigens and recent advancements in preclinical models for assessing the efficacy of candidate TB vaccines.

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Intravenous Bacille Calmette–Guérin vaccination protects simian immunodeficiency virus-infected macaques from tuberculosis

Cited by 19 publications

References 64 publications

Bacillus anthracis, “la maladie du charbon”, Toxins, and Institut Pasteur

Bacillus anthracis, “la maladie du charbon”, Toxins, and Institut Pasteur

A “suicide” BCG strain provides enhanced immunogenicity and robust protection againstMycobacterium tuberculosisin macaques

Antigen identification strategies and preclinical evaluation models for advancing tuberculosis vaccine development

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