The Use of Protein Antigens in Immunisation against Infection Caused By Streptococcus Pneumoniae

Streptococcus pneumoniae (the pneumococcus) is a major human pathogen which causes pneumonia, septicaemia and otitis media infections. The pneumococcus asymptomatically colonises the upper respiratory tract, which may act as a reservoir for subsequent infection of the lower respiratory tract. Current vaccines available include a polysaccharide vaccine (Pneumovax), and a conjugate vaccine (Prevenar). However, problems with both vaccines exist; Pneumovax does not elicit protection in children under the age of 2 years, the elderly or people who are immunocompromised, and Prevenar is an expensive vaccine that has limited serotype coverage. Serotype replacement has also become a growing problem. Therefore, new vaccine targets which can elicit broad cross-serotype protection are required. Pneumolysin and neuraminidase A are proteins that are highly conserved, in all serotypes of pneumococci. Throughout the research presented in this thesis, MF1 outbred mice and Balb/c inbred mice were immunised with PdB or neuraminidase A protein. Following I.P. or subcutaneous immunisation the mice were challenged using a variety of doses of virulent passaged pneumococci by the intraperitoneal, intravenous or intranasal routes. Immunisation with neuraminidase A elicited specific anti-neuraminidase antibodies. However, these antibodies were unable to protect the mice from acute pneumococcal challenge. Immunisation with PdB elicited a high titre of anti-PdB antibodies which were able to inhibit PLY activity in vitro. However, the antibodies were unable to protect the mice from acute pneumococcal challenge, or invasive pneumococcal challenge. Following colonisation challenge a significant drop in pneumococci recovered from nasopharynx of PdB immunised mice was seen. This significant drop in bacterial numbers correlated with a significant increase in the titre of specific IgG antibodies, as well as a significant increase in the number of specific IgG and IgA producing B cells, present in the cervical lymph nodes of PdB immunised mice, in comparison to that of the controls. Immunisation with neuraminidase A was unable to protect the mice from intraperitoneal and intranasal pneumococcal challenge, therefore, may not be necessary to include in future protein vaccines developed. Immunisation with PdB was able to significantly reduce nasopharyngeal colonisation, but was unable to clear colonisation. Therefore, PdB should be considered, along with other protective pneumococcal proteins, for inclusion in any future protein vaccine developed against pneumococcal colonisation