Withdrawn Australian Society for Microbiology Annual Scientific Meeting 2013

Screening of pneumococcal antigens in an intranasal pneumonia co-colonization NMRI mouse model (#317)

kgomotso K.W Lebogo 1 2 , Zena Z Kimaro 1 2 , Peter P.V Adrian 1 2 , Shabir S.A Madhi 1 2 3
  1. Respiratory,Pathogens and Menigeal research unit, Johannesburg, South Africa
  2. Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, DST/NRF, Johannesburg, South Africa
  3. National Institute for Communicable Diseases: Division of NHLS, Johannesburg,South Africa, South Africa

Streptococcus pneumoniae is frequently isolated in the nasopharynx of healthy children and adults.
Occasionally the pneumococcus progresses beyond the nasopharynx and causes invasive pneumococcal disease. Vaccines containing polysaccharide antigens are commercially available. However, serotype restriction in these vaccines is a great limitation, hence, the focus on protein based vaccines. The challenge with protein-based vaccines is that pre-clinical studies on pneumococcal proteins focus mainly on invasive disease mouse models, whereas their role has been suggested to be in colonization. The aim of this study was to evaluate pneumococcal antigens in an established intranasal pneumonia colonization model. Eighty female mice were equally distributed into vaccinated and placebo groups. Forty mice were subcutaneously vaccinated with recombinant PspA, SlrA, Stkp or IgA proteins and the forty in the placebo group were vaccinated with saponin, with three doses at 14-day interval. Both groups were co-infected with 50µl of a bacterial suspension containing D39: rpsL and D39ΔpspA, D39ΔslrA, D39ΔstkP or D39ΔigA. Bacterial samples were obtained through nasopharyngeal washings, broncho alveolar lavage (BAL) procedure and lung tissue collection, 24 hours post inoculation. Sera were collected by cardiac puncture and ELISA was used to measure IgG antibodies. The attenuated D39ΔpspA, D39ΔslrA, D39ΔstkP and D39ΔigA strains in the placebo group where effectively cleared from the nasopharynx, lungs and BAL compared to the wildtype strain D39: rpsL. The bacterial loads in the nasopharynx of mice immunized with rStkP and rIgA were greatly reduced. Increased levels of anti-IgA and anti-StkP were observed in the vaccinated group compared to placebo group, indicating the antibodies ability to confer protection against colonization. Vaccination with rPspA and rSlrA, however, did not protect mice against colonization. These results demonstrate this mouse model as being functional. Our study provides additional support for StkP and IgA as suitable candidates to be included in future vaccines to prevent colonization.