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

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.

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

“…Infant NHPs have been frequently used in studies to evaluate vaccines against Mycobacterium tuberculosis [229][230][231] and HIV [232][233][234]. Recently, Han et al used highthroughput technologies, including single-cell RNA sequencing of PBMCs, to perform an in-depth comparison of neonatal and adult immune responses to HIV immunization in macaques [235].…”

Protective immunity induced by an inhaled SARS-CoV-2 subunit vaccine

“…instillation. While intranasal immunisation has been previously tested for SARS-CoV-2 vaccines [5] , [7] , [8] , intratracheal administration, which simulates pulmonary inhalation, has to our knowledge not been reported, but has shown success for other pathogens [24] , [27] , [36] , [37] . We immunised 7 or 8 mice per group and included an additional control group of unvaccinated mice ( Table S1 ).…”

“…Furthermore, the requirement for trained healthcare professionals is reduced. Preclinical studies using dry powder vaccines have shown promise for various pathogens and toxins including Mycobacterium tuberculosis, Human papillomavirus, and influenza A virus [24] , [25] , [26] , [27] , and a safe and effective SARS-CoV-2 dry powder vaccine would be a boon to global vaccination efforts [4] , [22] , [23] .…”

Advanced drug delivery and therapeutic strategies for tuberculosis treatment

“…Anti-TB action has also been shown in nanostructured polyelectrolyte complexes synthesized from sodium alginate and chitosan. Alginate particles have been investigated as a means of encapsulating live mycobacterium particles for use in inhalable vaccinations [150,151].…”