Development and Testing of a Spray-Dried Tuberculosis Vaccine Candidate in a Mouse Model.

Shital Bachchhav,Mushtaq Ahmed,Rosemary Swanson,Hong Liang,Shabaana A Khader,Emilie Seydoux,Leah Mellett,Michelle Archer ,Chris Press,David Barona,Philip J Kuehl,Shibali Das,Christopher B Fox,Ananya Gupta,Hui Wang,Ryan M Kramer,Reinhard Vehring,Alana Gerhardt,Nicholas B Carrigy,Joseph Mccollum,Mellissa Gomez

doi:10.3389/fphar.2021.799034

Abstract

Converting a vaccine into a thermostable dry powder is advantageous as it reduces the resource burden linked with the cold chain and provides flexibility in dosage and administration through different routes. Such a dry powder presentation may be especially useful in the development of a vaccine towards the respiratory infectious disease tuberculosis (TB). This study assesses the immunogenicity and protective efficacy of spray-dried ID93+GLA-SE, a promising TB vaccine candidate, against Mycobacterium tuberculosis (Mtb) in a murine model when administered via different routes. Four administration routes for the spray-dried ID93+GLA-SE were evaluated along with relevant controls—1) reconstitution and intramuscular injection, 2) reconstitution and intranasal delivery, 3) nasal dry powder delivery via inhalation, and 4) pulmonary dry powder delivery via inhalation. Dry powder intranasal and pulmonary delivery was achieved using a custom nose-only inhalation device, and optimization using representative vaccine-free powder demonstrated that approximately 10 and 44% of the maximum possible delivered dose would be delivered for intranasal delivery and pulmonary delivery, respectively. Spray-dried powder was engineered according to the different administration routes including maintaining approximately equivalent delivered doses of ID93 and GLA. Vaccine properties of the different spray-dried lots were assessed for quality control in terms of nanoemulsion droplet diameter, polydispersity index, adjuvant content, and antigen content. Our results using the Mtb mouse challenge model show that both intranasal reconstituted vaccine delivery as well as pulmonary dry powder vaccine delivery resulted in Mtb control in infected mice comparable to traditional intramuscular delivery. Improved protection in these two vaccinated groups over their respective control groups coincided with the presence of cytokine-producing T cell responses. In summary, our results provide novel vaccine formulations and delivery routes that can be harnessed to provide protection against Mtb infection.

Highlights

Tuberculosis (TB) is a highly infectious respiratory disease that was responsible for the deaths of 1.2 million people worldwide in 2019 (WHO, 2020)
Test 3 was completed at a lower feed piston rate and demonstrated a higher efficiency of powder delivery compared to Test 1 and 2
We evaluated the immunogenicity and efficacy of the spray-dried ID93+GLA-squalene oil emulsion (SE) powder delivered as an inhaled aerosol either to the nose and lungs using smaller particle size spray-dried formulations, or to the nose using larger particle size spray-dried formulations, compared to the reconstituted liquid vaccine administered intranasally or by the conventional intramuscular route

Summary

Introduction

Tuberculosis (TB) is a highly infectious respiratory disease that was responsible for the deaths of 1.2 million people worldwide in 2019 (WHO, 2020). The M72/AS01E TB vaccine consisting of a recombinant fusion protein antigen with a liposome adjuvant system containing a naturally derived Toll-like receptor 4 ligand and a saponin reduced disease progression after 3 years by 49.7% in Phase 2 clinical testing (Tait et al, 2019) Another promising candidate is the ID93+GLA-SE vaccine developed by the Infectious Disease Research Institute. We developed a thermostable lyophilized presentation of ID93+GLA-SE designed for reconstitution prior to injection, and it is currently undergoing Phase 1 clinical evaluation (Kramer et al, 2018) Another method of desiccation is through spray drying, wherein an atomized liquid product is dried into a powder. Spray drying has been shown to successfully confer thermostability to several experimental vaccines (Kanojia et al, 2018; LeClair et al, 2019) and approved vaccines (Kunda et al, 2019; Price et al, 2020)

Results

Discussion

Conclusion