Aerosol immunization by alginate coated mycobacterium (BCG/MIP) particles provide enhanced immune response and protective efficacy than aerosol of plain mycobacterium against M.tb. H37Rv infection in mice

Abstract

Background With the aim of preparing a more effective, safe and economical vaccine for tuberculosis, inhalable live mycobacterium formulations were evaluated. Methods Alginate particles in the size range of 2–4 μm were prepared by encapsulating live Bacille Calmette–Guérin (BCG) and “ Mycobacterium indicus pranii” (MIP). These particles were characterized for their size, stability and release profile. Mice were immunized with liquid aerosol or dry powder aerosol (DPA) alginate encapsulated mycobacterium particles and their in-vitro recall response and infection with mycobacterium H37Rv were investigated. Results It was found that the DPA of alginate encapsulated mycobacterium particles invoked superior immune response and provided higher protection in mice than the liquid aerosol. The BCG encapsulated in alginate particles (BEAP) and MIP encapsulated in alginate particles (MEAP) were engulfed by bone marrow dendritic cells (BMDCs) and co-localized with lysosome. The MEAP/BEAP activated BMDCs exhibited higher chemotaxis movement and had enhanced ability of antigen presentation to T cells. The in-vitro recall response of BEAP/MEAP immunized mice when compared in terms of proliferation index and Interferon gamma (IFN-gamma) released by splenocytes and mediastinal lymph node cells was found to be higher than mice immunized by liquid aerosol of BCG/MIP. Finally, different groups of immunized mice were infected with M. tb H37Rv and after 16 weeks the Colony forming units (CFUs) in lung and spleen estimated. The bacilli burden in the BEAP/MEAP immunized mice was significantly less than the respective liquid aerosol immunized mice and the histopathology of BEAP/MEAP immunized mice lungs showed very little damage. Conclusions These inhale-able vaccines formulation of alginate coated live mycobacterium are more immunogenic as compared to the aerosol of bacilli and they provide better protection in mice when infected with H37Rv. Electronic supplementary material The online version of this article (10.1186/s12879-019-4157-2) contains supplementary material, which is available to authorized users.

New Developments and Insights in the Improvement of Mycobacterium tuberculosis Vaccines and Diagnostics Within the End TB Strategy

“…Other lines of research to improve TB vaccination are directed towards addressing mucosal immunization and alternative routes of TB vaccination. In this context, inhalable TB vaccines offer the potential to mimic the natural route of M.tb infection and provide durable mucosal immune responses which may be critical for M.tb control [104,105]. In this regard, intranasal administration of whole cell inactivated MTBVAC HK vaccine in mice, improved the protective efficacy of mice previously vaccinated with subcutanous BCG, by triggering mucosal secretory immunoglobulins [106].…”

Novel Approaches for the Treatment of Pulmonary Tuberculosis

“…The application of biomaterial components in either tissue engineering or vaccine delivery system is known to have adjuvant effects, as measured by the observed enhancement of the host immune response [ 160 , 161 , 162 ]. Encapsulation of BCG and M indicus pranii (MIP) in bio-polymeric alginate microparticles as dry powder aerosol (DPA) were found to provide better protection against M. tuberculosis in a study conducted by Nagpal et al [ 163 ]. The developed formulations were found to be stable at temperatures up to 40 °C after 6 months of storage.…”

“…These findings demonstrated that BEAP/MEAP immunized animals have minimal lung pathology as compared to BCG/MIP animals, respectively. In short, alginate-coated BCG/MIP formulated in DPA are very promising vaccine candidates for TB with better protection against M. tuberculosis H37Rv [ 163 ].…”

Technological Approaches for Improving Vaccination Compliance and Coverage

“…Dry powder-based vaccine formulations have been designed and pre-clinically tested against several infectious diseases, progressing into clinical trials (Table 1). An inhalable vaccine formulation of alginate-coated live Mycobacterium microparticles was more immunogenic than liquid aerosols, and provided better protection in mice against experimental Mycobacterium tuberculosis infection [27]. In another study, an intrapulmonary-delivered Advax-adjuvanted influenza vaccine induced higher memory B and T cell responses than intranasal or intramuscular immunisation and conferred superior disease protection [28].…”