Abstract
BackgroundAt present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. Search for effective vaccine continues and some serotype independent pneumococcal proteins are considered as candidates for the design of new vaccines, especially a mucosal vaccine, since pneumococci enter the body through mucosal surfaces. Selection of the appropriate adjuvant is important for mucosal vaccines, and lactic acid bacteria (LAB) with immunostimulant properties are promissory candidates. In this work, we assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei), when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA) for the prevention of pneumococcal infection. Adjuvanticity of both live (LcV) and heat-killed (LcM) was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. The potential mechanisms induced by nasal immunization were discussed.ResultsNasal immunization of young mice with PppA+LcV and PppA+LcM induced anti-PppA IgA and IgG antibodies in mucosal and systemic compartments and levels of these specific antibodies remained high even at day 45 after the 3rd Immunization (3rd I). These results were correlated with IL-4 induction by the mixture of antigen plus LcV and LcM. Also, PppA+Lc (V and M) induced stimulation of Th1 and Th17 cells involved in the defence against pneumococci. The protection against pneumococcal respiratory challenge at day 30 after the 3rd I showed that PppA+LcV and PppA+LcM immunizations significantly reduced pathogen counts in nasal lavages while prventing their passage into lung and blood. Survival of mice immunized with the co-application of PppA plus LcV and LcM was significantly higher than in mice immunized with PppA alone and control mice when intraperitoneal challenge was performed. No significant differences between the treatments involving LcV and LcM were found.ConclusionsLive and heat-killed L. casei enhanced the antigen-specific immune response when administered nasally with a pneumococcal antigen. Considering the potential risk associated with live bacteria, the design of a nasal vaccine based on pneumococcal antigens and heat-killed L. casei emerges as a safe and effective strategy for the prevention of pneumococcal infections and opens new possibilities of application of dead LAB as adjuvants in vaccine formulations against other pathogens.
Highlights
At present, available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae
We showed that a recombinant lactococcus expressing the pneumococcal protective protein A (PppA), a protein antigenically conserved among different serotype strains of S. pneumoniae (3, 5, 9, 14, 19 and 23) [15], was able to afford protection against pneumococcal infection in a mouse model [16,17]
Samples of nasal lavages (NL), Bronchoalveolar lavages (BAL) and serum analyzed on days 0, 14, 28, 42, 58 and 73 showed that nasal immunization of young mice with PppA, PppA+LcV and PppA+LcM induced specific antiPppA IgA and IgG antibodies in three types of samples, while no detectable values of these specific antibodies were observed in any of the samples collected from animals that received LcV, LcM or phosphate buffer saline (PBS) (Figure 1)
Summary
Available pneumococcal vaccines have failed to eradicate infections caused by S. pneumoniae. We assessed the adjuvant effect of a probiotic strain, Lactobacillus casei (L. casei), when nasally administered with a pneumococcal antigen (pneumococcal protective protein A: PppA) for the prevention of pneumococcal infection Adjuvanticity of both live (LcV) and heat-killed (LcM) was evaluated and humoral and cellular antigen-specific immune response was assessed in mucosal and systemic compartments. In the last few years, the use of some LAB strains in the prevention of respiratory infection has become more evident [18,19,20,21] In this sense, the oral and nasal administration of live Lactobacillus casei CRL 431 (L. casei), a probiotic strain, was able to improve the immune response of the host against respiratory pathogens in a mouse model. In this work a new option, based on non-engineered and non viable lactic acid bacteria, was explored as a potential strategy for nasal vaccination against S. pneumoniae
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