Mycobacterium indicus pranii Induced Memory T-Cells in Lung Airways Are Sentinels for Improved Protection Against M.tb Infection

Abstract

The lungs are the most vulnerable site for air-borne infections. Immunologic compartmentalization of the lungs into airway lumen and interstitium has paved the way to determine the immune status of the site of pathogen entry, which is crucial for the outcome of any air-borne infections. Vaccination via the nasal route with Mycobacterium indicus pranii (MIP), a prospective candidate vaccine against tuberculosis (TB), has been reported to confer superior protection as compared to the subcutaneous (s.c.) route in small-animal models of TB. However, the immune mechanism remains only partly understood. Here, we showed that intranasal (i.n.) immunization of mice with MIP resulted in a significant recruitment of CD4+ and CD8+ T-cells expressing activation markers in the lung airway lumen. A strong memory T-cell response was observed in the lung airway lumen after i.n. MIP vaccination, compared with s.c. vaccination. The recruitment of these T-cells was regulated primarily by CXCR3–CXCL11 axis in “MIP i.n.” group. MIP-primed T-cells in the lung airway lumen effectively transferred protective immunity into naïve mice against Mycobacterium tuberculosis (M.tb) infection and helped reducing the pulmonary bacterial burden. These signatures of protective immune response were virtually absent or very low in unimmunized and subcutaneously immunized mice, respectively, before and after M.tb challenge. Our study provides mechanistic insights for MIP-elicited protective response against M.tb infection.

The Roles of Chemokines in Immune Response to Mycobacterial Infection

“…In an effort of vaccination study using Mycobacterium indicus pranii (MIP), a promising TB vaccine candidate, intranasal immunization with MIP significantly enhances the recruitment of CD4+ and CD8+ T-cells and induces a strong memory T-cell response in the lung airway lumen. Importantly, the MIP-mediated protective T-cells are mainly regulated by CXCR3-CXCL11 axis and exhibit protective immunity against Mtb infection (70). Putting together, CXCR3-CXCL11 axis is critically required for protective immune responses against Mtb but more studies are needed to clarify the chemokine signaling in terms of anti-TB vaccination.…”

A unique vaccine for birth control and treatment of advanced stage cancers secreting ectopically human chorionic gonadotropin

“…Besides enhancing substantially antibody titers generated by the genetically engineered hCGβ-LTB vaccine, MIP brings in additional advantages to the body. It is effective against tuberculosis and several cancers [8,9]. Very recently 2 clinical trials with MIP on coronavirus disease 2019 (COVID-19) infected patients have been published.…”

Penggunaan Berbagai Macam Vaksin Pada Terapi Kondiloma Akuminata Anogenital

“…Berdasarkan penggolongan grup Runyos termasuk dalam grup IV bersama dengan M. smegmatis, M. chelonae, dan M. vaccae berdasarkan pertumbuhan dan profil metabolit. (Gupta et al, 2012(Gupta et al, , 2019.…”

“…Belum ada data keamanan pada kehamilan dan menyusui karena studi yang menggunakan vaksin MIP menggunakan kehamilan dan menyusui sebagai kriteria eksklusi. (Gupta et al, 2012(Gupta et al, , 2019 Vaksin MIP akan menginduksi respon dari CD4 dan CD8 dengan meningkatkan migrasi sel T menuju tempat lesi via ekspresi CXCR3. Selain itu, CXCR3 dapat meningkatkan differensiasi dari sel T menjadi sel memori dan sel efektor.…”

“…Selain itu, CXCR3 dapat meningkatkan differensiasi dari sel T menjadi sel memori dan sel efektor. Produksi (Gupta et al, 2019).…”