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Mucosal immunisation of mice with malaria protein on lactic acid bacterial cell walls
1National Science Foundation, Maitland Place, Colombo, Sri Lanka; Institute of Fundamental Studies, Kandy, Sri Lanka.
Abstract:
Mice were orally and nasally immunised with a malaria parasite protein, MSA2, expressed in Lactococcus lactis, covalently attached to the peptidoglycan (MSA2cP), or non-covalently rebound to L. lactis cell walls, live Lactobacillus reuteri and Lb. salivarius (MSA2cA). Although there was marked variation within mice of the same inbred strain, the data suggest that the characteristics of serum IgG antibodies formed against MSA2 are influenced by the mouse strain and mode of MSA2 presentation. MSA2-specific IgA antibodies in sera and faecal pellets, and IFNgamma-secreting spleen cells were detectable in some immunised animals. MSA2cA on lactobacilli, although not effective in eliciting serum IgG antibodies, showed a potential for eliciting IgA antibodies in the gut. The presence of MSA2 in L. lactis tended to divert the antibody response from lactococcal antigens. The data suggest that anti-MSA2 and anti-lactococcal antibody responses are not necessarily associated in the mice. The findings are related to the use of lactic acid bacteria expressing heterologous proteins for therapy and vaccination.
Insights
Mice immunized with malaria protein MSA2 presented on lactic acid bacteria showed varied antibody responses. Presentation method and mouse strain influenced IgG, while some methods showed potential for gut IgA production.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Lactic acid bacteria (LAB) are explored as delivery vehicles for heterologous proteins in vaccination.
- Malaria parasite protein 2 (MSA2) is a candidate antigen for malaria vaccines.
- Understanding immune responses to antigen presentation by LAB is crucial for developing effective vaccines.
Purpose of the Study:
- To investigate the immunogenicity of malaria antigen MSA2 when expressed by Lactococcus lactis and Lactobacillus species.
- To evaluate the impact of different antigen presentation methods (covalent attachment, cell wall binding, live bacteria) on antibody and cellular immune responses.
- To assess the potential of LAB-based delivery systems for inducing mucosal immunity.
Main Methods:
- Oral and nasal immunization of mice with MSA2-expressing LAB.
- Analysis of serum IgG and IgA antibody titers against MSA2.
- Detection of IFN-gamma secreting spleen cells.
- Assessment of antibody responses to LAB antigens.
Main Results:
- Significant variation in serum IgG responses against MSA2 was observed, influenced by mouse strain and MSA2 presentation method.
- MSA2-specific IgA antibodies were detected in sera and fecal samples, particularly with MSA2 bound to lactobacilli (MSA2cA).
- IFN-gamma secreting spleen cells were found in some immunized mice.
- Antibody responses to MSA2 did not necessarily correlate with responses to lactococcal antigens.
Conclusions:
- The presentation of MSA2 on LAB influences the type and magnitude of immune responses, with potential for inducing gut IgA.
- LAB expressing heterologous antigens can elicit specific immune responses, but careful selection of presentation strategy and host factors is necessary.
- This study provides insights into the use of engineered LAB for vaccine development, highlighting the potential for mucosal immunity induction.
