The safety and efficacy of BCG encapsulated alginate particle (BEAP) against M.tb H37Rv infection in Macaca mulatta : A pilot study

Ashwani Kesarwani,Surender Singh,Pramod Upadhyay,Puja S Nagpal,Rana Zaidi,K Varsha Mohan,Perumal Nagarajan,Parul Sahu,Prakriti Sinha,Kshama Jain

doi:10.1038/s41598-021-82614-5

Ashwani Kesarwani, Surender Singh + Show 8 more

Open Access

https://doi.org/10.1038/s41598-021-82614-5

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Abstract

Due to the limited utility of Bacillus Calmette–Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals’ blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.

Highlights

There are a few new vaccine candidates in the p ipeline[4] but so far it has been challenging to provide protection any better than the Bacillus Calmette–Guérin (BCG)
We assessed the safety of the BCG encapsulated alginate particle (BEAP) formulation in infant macaques by monitoring behaviour and growth, liver function tests and cytokines level in serum for up to 12 months post immunization
In this study we investigated the safety and efficacy of a new BCG formulation, BEAP, which was delivered intratracheally in infant macaques and explored how BEAP could be compared with the conventional intradermal BCG immunization

Summary

Introduction

There are a few new vaccine candidates in the p ipeline[4] but so far it has been challenging to provide protection any better than the BCG. New formulations and delivery routes have been investigated[9,10,11] In this context, we had previously reported a unique dry powder aerosol (DPA) formulation of B CG12 as a potential vaccine candidate. We had previously reported a unique dry powder aerosol (DPA) formulation of B CG12 as a potential vaccine candidate This formulation is a BCG encapsulated alginate particle (BEAP), which is 2–5 μm in size and to be delivered as an aerosol. To advance the study towards human applicability, the obvious step is to investigate the performance of this formulation in a primate model like the Macaca mulatta since these animals manifest the full spectrum of disease conditions as in h umans[13] In this pilot investigation, the dry powder formulation, BEAP was evaluated in Indian rhesus macaques (Macaca mulatta). The efficacy of the formulation was evaluated by an ex-vivo infection assay with M.tb H37Rv

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