Smith, Daniel (2015) Immunological responses associated with the use of a putative dual vaccine against Hepatitis B Virus and Streptococcus pneumoniae. Honours thesis, University of Southern Queensland. (Unpublished)
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Abstract
Streptococcus pneumoniae is a significant pathogen globally and a lead cause of invasive disease,
pneumonia, sepsis and otitis media. The bacteria’s capacity for establishing an infection is aided by
virulence factors (especially the presence of a capsule) and a high prevalence of nasopharyngeal
carriage (up to 30% in healthy populations). Infections from S. pneumoniae account for a significant
burden of morbidity and mortality in the elderly and children globally, with substantial morbidity in
Indigenous children due to very high otitis media rates. There are at present two vaccines available
for protection against S. pneumoniae. Pneumococcal Polysaccharide Vaccine (PPSV) conveys
protection against 23 of the 90+ serotypes, but does not provide a memory response in children
under 2 years old. Pneumococcal Conjugate Vaccine (PCV) only conveys protection against 13
serotypes, but because it utilises protein conjugation it is able to stimulate a memory immune
response in children under 2 years old. The focus of this project was on two strong vaccine
candidates, the pneumococcal capsular proteins PiaA and PiuA. BALB/c mice were vaccinated with
these proteins to elicit a T‐cell dependent, humoral and Cell Mediated Immunity (CMI) response. An
adjuvant (Advax™) and conjugation of both PiaA and PiuA to Hepatitis B surface antigen (HBsAg)
were techniques used to stimulate this response. The efficacy of the vaccine was first measured by
determining the immunological response to the vaccine through antibody production. Mice were
then challenged with S. pneumoniae and their response was analysed to determine if protection had
been achieved. The vaccine produced a mostly humoral response, though CMI was higher than for
PiuA and PiaA vaccines in previous studies in the literature. The vaccination appeared to prevent
invasive disease by significantly lowering numbers of the bacteria in the blood, though signs of
infection were present from examination of lung tissue and presence of bacteria in lungs. The HBsAg
was able to stimulate a humoral immunological response against HBV, and conjugation to PiaA and
PiuA did not inhibit this. Both PiaA and PiuA produced a level of protection against S. pneumoniae
and can be potentially conjugated to HBsAg to protect against HBV simultaneously.
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