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Scientific article
Open access
English

Intranasal immunization with pneumococcal conjugate vaccines with LT-K63, a nontoxic mutant of heat-Labile enterotoxin, as adjuvant rapidly induces protective immunity against lethal pneumococcal infections in neonatal mice

Published inInfection and immunity, vol. 70, no. 3, p. 1443-1452
Publication date2002
Abstract

Immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus toxoid (TT) (Pnc-TT) elicits protective immunity in an adult murine pneumococcal infection model. To assess immunogenicity and protective immunity in early life, neonatal (1 week old) and infant (3 weeks old) mice were immunized intranasally (i.n.) or subcutaneously (s.c.) with Pnc-TT of serotype 1 (Pnc1-TT). Anti-PPS-1 and anti-TT immunoglobulin G (IgG) and IgM antibodies were measured in serum and saliva, and vaccine-induced protection was evaluated by i.n. challenge with serotype 1 pneumococci. Pnc1-TT was immunogenic in neonatal and infant mice when administered s.c. without adjuvant: a majority of the young mice were protected from bacteremia and a reduction of pneumococcal density in the lungs was observed, although antibody responses and protective efficacy remained lower than in adults. The addition of LT-K63, a nontoxic mutant of heat-labile enterotoxin, as adjuvant significantly enhanced PPS-1-specific IgG responses and protective efficacy following either s.c. or i.n. Pnc1-TT immunization. Mucosal immunization was particularly efficient in neonates, as a single i.n. dose of Pnc1-TT and LT-K63 induced significantly higher PPS-1-specific IgG responses than s.c. immunization and was sufficient to protect neonatal mice against pneumococcal infections, whereas two s.c. doses were required to induce complete protection. In addition, i.n. immunization with Pnc1-TT and LT-K63 induced a vigorous salivary IgA response. This suggests that mucosal immunization with pneumococcal conjugate vaccines and LT-K63 may be able to circumvent some of the limitations of neonatal antibody responses, which are required for protective immunity in early life.

Keywords
  • Adjuvants, Immunologic/administration & dosage/genetics/therapeutic use
  • Administration, Intranasal
  • Animals
  • Animals, Newborn
  • Antibodies, Bacterial/blood
  • Bacterial Toxins/administration & dosage/genetics/therapeutic use
  • Enterotoxins/administration & dosage/genetics/therapeutic use
  • Escherichia coli Proteins
  • Immunoglobulin A/analysis
  • Mice
  • Pneumococcal Infections/prevention & control
  • Pneumococcal Vaccines/administration & dosage/therapeutic use
  • Polysaccharides, Bacterial/therapeutic use
  • Saliva/immunology
  • Vaccination
  • Vaccines, Conjugate/administration & dosage/therapeutic use
Citation (ISO format)
JAKOBSEN, Håvard et al. Intranasal immunization with pneumococcal conjugate vaccines with LT-K63, a nontoxic mutant of heat-Labile enterotoxin, as adjuvant rapidly induces protective immunity against lethal pneumococcal infections in neonatal mice. In: Infection and immunity, 2002, vol. 70, n° 3, p. 1443–1452. doi: 10.1128/IAI.70.3.1443-1452.2002
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Article (Published version)
accessLevelPublic
Identifiers
ISSN of the journal0019-9567
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