Evaluation of the humoral immune response and cross reactivity against Mycobacterium tuberculosis of mice immunized with liposomes containing glycolipids of Mycobacterium smegmatis

Abstract

Mycobacterium smegmatis (Ms) is a nonpathogenic mycobacteria of rapid growth, which shares many characteristics with Mycobacterium tuberculosis (MTB), the major causative agent of tuberculosis. MTB has several cell wall glycolipids in common with Ms, which play an important role in the pathogenesis of tuberculosis and the induction of a protective immune response against MTB infection in some animal models. In this study, the humoral immune response and cross reactivity against MTB, of liposomes containing a mixture of cell wall glycolipids of Ms and commercial lipids was evaluated, in order to study its possible use as a component of a vaccine candidate against tuberculosis. Liposomes containing total lipids extracted from Ms, distearoyl phosphatidyl choline and cholesterol were prepared by the dehydration-rehydration technique. Balb/c mice were immunized with the liposomes obtained and the antibody response and cross reactivity against MTB were tested by ELISA. Total lipids extract from Ms showed the presence of several polar glycolipids in common with MTB, such as phosphatidylinositol mannosides. Liposomes that contained glycolipids of Ms were capable of inducing a specific IgG antibody response that allowed the recognition of surface antigens of MTB. The results of this study demonstrated the presence of immunogenic glycolipids in Ms, which could be included to enhance the protective effects of subunit vaccine formulations against tuberculosis.

Protective Effect of a Lipid-Based Preparation fromMycobacterium smegmatisin a Murine Model of Progressive Pulmonary Tuberculosis

“…A higher reactivity of IgG antibodies against this formulation was detected in patients with pulmonary TB, compared with healthy individuals, which suggests the expression of similar or cross-reactive epitopes during the active infection with Mtb in humans [ 10 ]. When the total lipid extract of Ms was formulated in liposomes containing commercial lipids without adjuvants, a similar induction of specific and cross-reactive IgG response against Mtb was obtained [ 11 ].…”

“…Taking into consideration the induction of specific IgG antibodies and the elicitation of cross-reactive immune responses against Mtb after immunization with formulations containing lipids of Ms in mice [ 10 , 11 ], the role of specific antibodies in the protection induced by these formulations cannot be ruled out. The contribution of specific antibodies in protection against TB is a subject of debate, but a growing body of evidence supports the potential role of antibodies in the protection against TB [ 27 – 36 ].…”

“…Our group has previously reported on the capability of preparations containing chloroform extractable lipids from Mycobacterium smegmatis (Ms) to induce specific IgG antibodies as well as a cross-reactive response against a mixture of Mtb antigens in Balb/c mice [ 10 , 11 ]. Additionally, proteoliposomes from Ms and BCG elicited cross reactive responses against antigenic fractions from Mtb, demonstrating the antigenic similarities between the cell wall components of these non-pathogenic mycobacteria and Mtb [ 12 , 13 ].…”

Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice

“…Previous studies have demonstrated that serum antibodies may have protective effect in animal models of tuberculosis (39,53). In addition, analysis of the isotypic distribution of immunoglobulin may offer an insight into the possible immunological mechanisms involved in cellular immunity (54).…”

“…Humoral immunity has also been demonstrated to have a protective role in mycobacterial infections (39). In order to evaluate the IgG antibody response in immunized mice in the BCG or BCG prime Ad5-CEAB-boosted groups, the titers of IgG in mice were examined at 2 weeks following the final immunization.…”