Local and systemic immunity against<i>Streptococcus pneumoniae</i>: Humoral responses against a non-capsulated temperature-sensitive mutant

An intranasal (i.n.) dosing model was developed in mice as a potential alternative to more difficult, time-consuming, and costly guinea pig intratracheal (GPIT) or mouse intratracheal models for assessment of the respiratory immunogenicity of detergent enzymes. Using a benchmark enzyme, Alcalase (protease subtilisin Carlsberg), studies were conducted to standardize the model in terms of mouse strain, dosing and serum harvest regimen, and the primary immunoglobulin endpoint to use. The primary assay endpoint selected was the enzyme-specific IgG1 titer determined by an Alcalase-specific ELISA. This is not the primary allergenic antibody in mice (IgE is); however, IgG1 is coregulated with IgE via the IL-4/TH2 pathway and may have a role in mediating allergic-type responses. BDF1 mice (C57B1/6 x DBA/2) were selected as representative of high responder strains, with high response associated with the H-2b (C57B1/6) parent. The dosing regimen used for most studies incorporated three i.n. exposures (Days 1, 3, and 10) and bleeding of the animals on Day 15. The animals were anesthetized and then immunized by allowing them to inhale 5-microliters aliquots of dosing solution into each nostril at each immunization. Positioning of the animals with their heads down (vs up) may have allowed more of the dosing solution to remain in the nasal region for a slightly longer period of time, but did not change the eventual GI tract migration and excretion of each dose. The presence of a detergent matrix in the enzyme dosing solution enhanced the IgG1 response. Immunizing with enzyme plus detergent gave highly consistent dose-response curves for Alcalase when evaluated over many studies. An enzyme-specific allergic antibody (IgE) response was weak and inconsistent under the dosing regimen used to generate the IgG1 response, but was stronger with longer-term dosing, consistent with the delay in IgE vs IgG1 responses seen in some other studies. Using IgG1 as a surrogate for allergic sensitization, we have preliminary data showing similar differential potencies between Alcalase and other test enzymes as detected in previous GPIT tests. On the basis of these data, we believe the i.n. immunization/IgG1 response model is a robust technique that may be useful in determining the relative immunogenicities of detergent enzymes and other proteins.

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Specific Antibody Responses to Subtilisin Carlsberg (Alcalase) in Mice: Development of an Intranasal Exposure Model

Robinson

Babcock

Horn

et al. 1996

Fundamental and Applied Toxicology

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Lactobacillus casei administration reduces lung injuries in a Streptococcus pneumoniae infection in mice

Racedo

Villena

Medina

et al. 2006

Microbes and Infection

118

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Nasal administration of Lactococcus lactis improves local and systemic immune responses against Streptococcus pneumoniae

Medina

Villena

Salva

et al. 2008

Microbiology and Immunology

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Lactococcus lactis NZ9000 is a non-pathogenic non-invasive bacterium extensively used for the delivery of antigens and cytokines at the mucosal level. However, there are no reports concerning the per se immunomodulatory capacity of this strain. The aim of the present study was to investigate the intrinsic immunostimulating properties of the nasal administration of L. lactis NZ9000 in a pneumococcal infection model. Mice were preventively treated with L. lactis Key words adjuvant, Lactococcus lactis, nasal administration, pneumococcal infection.Bacterial respiratory diseases remain a major cause of morbidity and mortality in both developed and developing communities. In Argentina, Streptococcus pneumoniae is one of the most important respiratory pathogens (1). This bacterium can migrate to mucosal areas that are normally sterile and lead to a variety of mucosal infections such as otitis media or pneumonia. In addition, pneumococci can induce invasive cases of septicemia and meningitis. The high morbidity associated with this microorganism remains a leading cause of mortality in the young and the elderly (2). The deaths caused by S. pneumoniae are concentrated in developing countries, where the rates are

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Local and systemic immunity againstStreptococcus pneumoniae: Humoral responses against a non-capsulated temperature-sensitive mutant

Cited by 4 publications

References 16 publications

Specific Antibody Responses to Subtilisin Carlsberg (Alcalase) in Mice: Development of an Intranasal Exposure Model

Specific Antibody Responses to Subtilisin Carlsberg (Alcalase) in Mice: Development of an Intranasal Exposure Model

Lactobacillus casei administration reduces lung injuries in a Streptococcus pneumoniae infection in mice

Nasal administration of Lactococcus lactis improves local and systemic immune responses against Streptococcus pneumoniae

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