The microbes that surround us constantly invade our body, many of them through respiratory airways, where mucosal surfaces form the first line of defence against pathogenic bacteria. This challenge by pathogens is met by both nonspecific and specific defence mechanisms of the immune system, both already functioning locally at mucosal surfaces. The specific immune system has a unique capability to recognise a specific pathogen, target the defence against it, and recognise the same pathogen even years later. This memory function has been described for both systemic and mucosal immune responses.
Each pathogen has its own strategy to gain access into the human body, but also the immune system has a specific strategy for the fight against each pathogen. It is therefore essential to study the pathogenesis of each disease and the human defence mechanisms against each pathogen, in order to develop preventive and therapeutic means, e.g., vaccines, against the disease. Acute otitis media (AOM) is an example of an infection restricted to mucosal membranes. It is common among small children; nearly all children experience at least one AOM episode before the age of two years.
The most common causative bacterium of AOM is Streptococcus pneumoniae, the pneumococcus (Pnc). An important virulence factor for the pneumococcus is the polysaccharide (PS) capsule, which helps it to avoid phagocytosis. Since the pneumococci are encapsulated bacteria, it is essential for the immunological defence to produce antibodies against the polysaccharide capsule in order to fight against the pathogen. Pneumococcal PS vaccines, consisting of polysaccharides of different serotypes of the pneumococcus, are immunogenic in the adult population, i.e., able to induce antibody production against the capsular PS. However, these vaccines are able to induce only poor, if any, antibody responses in infants and young children, who are the most susceptible to pneumococcal diseases, partly because of the immaturity of their immune system. The poor response to PS seen in small children is due to the T-independent nature of these antigens, which means the PS vaccines are unable to induce T-cell help for antibody production. However, coupling of the PS antigens to a protein carrier turns them into T-dependent antigens, which are recognised by helper T-cells that then stimulate antibody production by B-cells. Conjugate vaccines consisting of pneumococcal PS coupled to different carrier proteins have already been shown to be immunogenic in young children and infants.
Haemophilus influenzae type b (Hib) conjugate vaccines, and more recently also pneumococcal conjugate vaccines, have been shown to reduce colonisation with the respective bacteria in the nasopharynx, suggesting that parenteral immunisation can induce protection at mucosal surfaces. Thus the pneumococcal conjugate vaccines can be expected to prevent, in addition to serious invasive infection, mucosal infections such as pneumococcal AOM and pneumonia.
This thesis describes part of a larger series of studies, carried out to characterise the immune responses related to AOM and to study the immunogenicity of the pneumococcal conjugate vaccines. The focus of this work is on induction of mucosal antibody responses, both those seen in AOM and those induced by parenterally administered pneumococcal conjugate vaccines.