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      Intranasal vaccination of infant mice induces protective immunity in the absence of nasal-associated lymphoid tissue.

      Vaccine
      Administration, Intranasal, Animals, Animals, Newborn, Body Weight, physiology, Cell Count, Enzyme-Linked Immunosorbent Assay, Immunoglobulin A, biosynthesis, immunology, Immunohistochemistry, Lymphoid Tissue, Lymphotoxin-alpha, genetics, Lymphotoxin-beta, Mice, Mice, Inbred BALB C, Mice, Knockout, Microscopy, Fluorescence, Nasal Mucosa, Pneumococcal Infections, pathology, Pneumococcal Vaccines, administration & dosage, Streptococcus pneumoniae, growth & development, Vaccination

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          Abstract

          Intranasal (i.n.) immunization is an effective regimen for the prophylaxis of respiratory diseases in early life. The aim of this study was to assess the need for nasal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLN) in induction of protective immunity following mucosal vaccination of infant mice. We developed surgical techniques to eliminate NALT and CLN in young (8 days old) mice. i.n. vaccination of NALT- or CLN-deficient mice with pneumococcal polysaccharide conjugate vaccine plus interleukin-12 as a mucosal adjuvant (days 10 and 17) was followed by i.n. pneumococcal challenge (days 24-28). Mice were sacrificed on day 31 and nasal mucosal and systemic immune responses as well as pneumococcal colonization in the middle ear and nasopharynx were assessed. Elimination of NALT did not impair the ability of infant (3 weeks old) mice to produce nasal or serum antibody responses following i.n. immunization. In contrast, surgical removal of CLN significantly impaired the ability to express IgA antibody in nasopharyngeal washes and total antibody in serum. Similarly, protection against pneumococcal colonization in the nasopharynx and middle ears of immunized mice was decreased in the absence of CLN but not in the absence of NALT. These findings suggest that surgical removal of NALT tissue, at least in a mouse model, does not affect the ability to respond to subsequent i.n. vaccination. In addition, in the young mice CLN play a more important role than NALT for induction of protective mucosal and systemic antibody responses following i.n. immunization.

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