Mucosal delivery of tuberculosis vaccines: a review of current approaches and challenges

Abstract

Introduction: Tuberculosis (TB) remains a major health threat and it is now clear that the current vaccine, BCG, is unable to arrest the global TB epidemic. A new vaccine is needed to either replace or boost BCG so that a better level of protection could be achieved. The route of entry of Mycobacterium tuberculosis, the causative organism, is via inhalation making TB primarily a respiratory disease. There is therefore good reason to hypothesize that a mucosally delivered vaccine against TB could be more effective than one delivered via the systemic route. Areas covered: This review summarizes the progress that has been made in the area of TB mucosal vaccines in the last few years. It highlights some of the strengths and shortcomings of the published evidence and aims to discuss immunological and practical considerations in the development of mucosal vaccines. Expert opinion: There is a growing body of evidence that the mucosal approach to vaccination against TB is feasible and should be pursued. However, further key studies are necessary to both improve our understanding of the protective immune mechanisms operating in the mucosa and the technical aspects of aerosolized delivery, before such a vaccine could become a feasible, deployable strategy.

Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues

“…Previous findings demonstrated the safety of this approach and showed that the pulmonary route was as efficacious as the subcutaneous route [16]. The pulmonary administration of DNA vaccines is being examined for various infections, including influenza, measles, and tuberculosis [17]. However, to the best of our knowledge, limited information is currently available on the pulmonary administration of DNA vaccines for cancer.…”

Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

“…The total mucosal surface area is about 200 times larger than skin, and vaccination at the sites of pathogen invasion could generate a protective immunological response [46]. While oral BCG was the initial delivery method almost a century ago, oral vaccines generally must survive the acidic environment of the stomach and run the risk of generating tolerance without an adjuvant [47]. That said, comparing intradermal and oral delivery in humans, oral BCG induced stronger mucosal responses, as measured by Mtb-specific bronchoalveolar lavage (BAL) T-cells and secretory Immunoglobulin A (IgA), though intradermal BCG resulted in stronger systemic Th1 responses [48].…”

Integrating fish models in tuberculosis vaccine development

“…Animal studies have also provided important insights into the relevant delivery routes of TB vaccines. The standard routes of immunization in mammals and humans include intradermal and intramuscular, which aim to elicit systemic immune responses (Stylianou et al, 2019;Dijkman et al, 2019;Brandt et al, 2004;Skeiky et al, 2004). However, in 1973, a study in NHPs showed that Diedrich et al, 2010;Lin et al, 2009;Capuano et al, 2003Cooper, 2014Medina andNorth, 1998 Peng et al, 2015;Kesavan et al, 2009;Manabe et al, 2008;Manabe et al, 2003Clark et al, 2014Grover et al, 2012;Williams et al, 2009Pesciaroli et al, 2014Villarreal-Ramos et al, 2014;Cassidy, 2006;Buddle et al, 1999Parikka et al, 2012Swaim et al, 2006;Davis et al, 2002 mucosal vaccination could enhance protection against airborne Mtb (Barclay et al, 1973).…”

“…Animal studies have also provided important insights into the relevant delivery routes of TB vaccines. The standard routes of immunization in mammals and humans include intradermal and intramuscular, which aim to elicit systemic immune responses ( Stylianou et al, 2019 ; Dijkman et al, 2019 ; Brandt et al, 2004 ; Skeiky et al, 2004 ). However, in 1973, a study in NHPs showed that mucosal vaccination could enhance protection against airborne Mtb ( Barclay et al, 1973 ).…”