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Published on: December 19, 2020
Mucosal vaccination against encapsulated respiratory bacteria--new potentials for conjugate vaccines?
1Department of Immunology, Landspitali-University Hospital, Hringbraut, 101 Reykjavik, Iceland.
Abstract:
Polysaccharide (PS)-encapsulated bacteria such as Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococcus), Neisseria meningitides (meningococcus) and group B streptococcus (GBS), cause a major proportion of disease in early childhood. Native PS vaccines are immunogenic and provide protection against disease in healthy adults but do not induce immunological memory. PSs are T-cell-independent antigens and do not elicit antibodies in infants and young children, but by conjugating PS to proteins they become T-cell dependent and immunogenic at an early age. Despite excellent efficacy of PS-protein conjugate vaccines against invasive disease, protection against mucosal infections such as pneumococcal otitis media has been less efficacious. Circulating PS-specific antibodies may protect against infections at mucosal sites, but mucosal immunoglobulin A antibodies may also contribute significantly to protection against mucosal infections. Mucosal immunization of experimental animals with conjugate vaccines against Hib, pneumococcus, meningococcus and GBS induces systemic and mucosal immune responses, which provide protection against carriage, otitis media and invasive disease in a variety of challenge models, providing new means for protection against encapsulated bacteria. In addition, mucosal immunization of neonatal mice with a pneumococcal conjugate and the nontoxic adjuvant LT-K63 has been superior to parenteral immunization in eliciting protective antibodies and PS-specific memory, and thus circumventing the limitations of antibody responses to PS that are responsible for enhanced susceptibility of neonates and infants to infections caused by encapsulated bacteria. Through T-cell dependent enhanced immunogenicity of PS-protein conjugate vaccines, mucosal immunization could be an attractive approach for early life immunization against encapsulated bacteria.
Insights
Mucosal immunization with polysaccharide-protein conjugate vaccines offers enhanced protection against encapsulated bacterial infections in early childhood. This approach improves immune responses and memory, overcoming limitations of traditional vaccines.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Polysaccharide (PS)-encapsulated bacteria like Hib, pneumococcus, meningococcus, and GBS cause significant early childhood diseases.
- Native PS vaccines are less effective in infants due to their T-cell independent nature, failing to induce immunological memory.
- PS-protein conjugate vaccines enhance immunogenicity in young children but show limited efficacy against mucosal infections like otitis media.
Purpose of the Study:
- To evaluate the efficacy of mucosal immunization with PS-protein conjugate vaccines against encapsulated bacteria.
- To assess the induction of systemic and mucosal immune responses following mucosal vaccination.
- To explore the potential of mucosal immunization to overcome neonatal and infant susceptibility to encapsulated bacterial infections.
Main Methods:
- Experimental animals were immunized mucosally with conjugate vaccines against Hib, pneumococcus, meningococcus, and GBS.
- Neonatal mice received pneumococcal conjugate vaccine with LT-K63 adjuvant via mucosal versus parenteral routes.
- Immune responses, including antibody production and immunological memory, were analyzed.
Main Results:
- Mucosal immunization induced protective systemic and mucosal immune responses against various encapsulated bacteria.
- Protection was observed against bacterial carriage, otitis media, and invasive diseases in challenge models.
- Mucosal immunization in neonatal mice with pneumococcal conjugate and adjuvant was superior to parenteral immunization in generating protective antibodies and PS-specific memory.
Conclusions:
- Mucosal immunization with PS-protein conjugate vaccines provides a promising strategy for protecting against encapsulated bacterial infections.
- This approach elicits robust systemic and mucosal immunity, offering protection against both invasive and mucosal diseases.
- Mucosal vaccination, particularly in early life, circumvents limitations of traditional parenteral routes and enhances protection in vulnerable infants.
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