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Homogeneous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes
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Protective immunity of pneumococcal glycoconjugates

Chi-Jen Lee1, Lucia H Lee, Carl E Frasch

  • 1Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852-1448, USA. lee_chi@cber.FDA.gov

Critical Reviews in Microbiology
|November 26, 2003
PubMed

Insights

Pneumococcal conjugate vaccines significantly enhance antibody responses and provide long-lasting protection against pneumococcal infections. Intranasal administration of these vaccines offers a convenient method for preventing pneumococcal disease.

Area of Science:

  • Immunology
  • Vaccinology
  • Microbiology

Background:

  • Pneumococcal polysaccharides (PSs), T-cell independent type 2 (TI-2) antigens, elicit weak immune responses in young children.
  • Splenic marginal zone B cells are crucial for TI-2 antibody responses and defense against bacterial pathogens.

Purpose of the Study:

  • To evaluate the immunogenicity and efficacy of pneumococcal conjugate vaccines.
  • To assess antibody response, avidity, and opsonophagocytic activity in mice immunized with type 9V PS conjugates.
  • To investigate intranasal immunization with glycoconjugate vaccines as a potential prevention strategy.

Main Methods:

  • Mice were immunized with type 9V PS conjugated to inactivated pneumolysin (Ply) or autolysin (Aly), or with 9V PS alone.
  • Serum IgG and IgM concentrations, antibody avidity, and opsonophagocytic activity against 9V pneumococci were measured.
  • Intranasal immunization with type 9V conjugate or 9V PS was performed, and antibody production and protection against virulent pneumococci were assessed.

Main Results:

  • Conjugate vaccines induced higher and sustained serum IgG and IgM concentrations against 9V PS compared to 9V PS alone.
  • Conjugate immunization resulted in high relative avidities of IgG and IgM antibodies and significant opsonophagocytic activity.
  • Intranasal immunization with glycoconjugates led to robust IgG and IgA antibody production in various tissues and provided protection against pneumococcal challenge.

Conclusions:

  • Pneumococcal conjugate vaccines elicit robust, long-lasting antibody responses and effective functional activity.
  • Intranasal administration of glycoconjugate vaccines is a promising and convenient approach for preventing pneumococcal infections.

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