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Identifying Novel Pneumococcal Pneumonia Vaccine Candidates

Cheliotis, Katerina (2022) Identifying Novel Pneumococcal Pneumonia Vaccine Candidates, Thesis (Doctoral), Liverpool School of Tropical Medicine.

K Cheliotis PhD - Final Thesis.pdf - Accepted Version

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The burden of pneumococcal pneumonia remains high worldwide. The disease disproportionately affects infants, the elderly and the immunocompromised. Nasopharyngeal colonisation with S. pneumoniae is the pre-requisite for disease but also, paradoxically, an immunising event. Current pneumococcal vaccines offer limited protection against pneumonia and do not offer serotype-independent coverage. Serotype replacement is particularly concerning. Identification of serotype-independent correlates of protection against S. pneumoniae infection will accelerate development of vaccines with broad coverage. Protein vaccines are a particularly promising way to confer serotype-independent protection.
The experimental human pneumococcal challenge (EHPC) model enables us to investigate correlates of protection against experimental colonisation with S. pneumoniae and study protein-directed immune responses to nasopharyngeal colonisation with the bacteria. A multiplex Luminex assay was developed and used to measure serum IgG against 75 conserved pneumococcal antigens pre- and post-intranasal inoculation with two serotypes of pneumococcus (6B and 15B) in EHPC volunteers. Peripheral blood mononuclear cells taken pre- and post-challenge with serotype 6B pneumococcus were used to evaluate correlation between protein-specific IgG+ memory B-cell responses and protection against experimental colonisation as well as memory B-cell responses to pneumococcal challenge by ELISpot. Memory B-cell responses to six selected proteins and the novel PnuBioVax vaccine were investigated. The results of this work showed that colonisation with serotype 6B pneumococcus induces significant systemic protein-mediated antibody and memory B-cell responses. No single protein antigen correlated with protection against experimental colonisation with S. pneumoniae. However, whilst not significant, there was a trend that PnuBioVax-specific memory B-cells conferred protection against experimental pneumococcal colonisation. Five novel nanoparticle-based vaccines were also investigated to determine their effects on dendritic cell maturation and support of T-cell activation. One of these nanoparticles was subsequently loaded with pneumococcal protein PspA to investigate antigen-specific response. Further work is needed to ascertain the immune response to these novel vaccines, though they are a promising method of serotype-independent vaccine delivery.
It is likely that for a novel pneumococcal protein vaccine to confer serotype-independent protection against pneumococcal pneumonia, a combination of protein antigens will need to be included in vaccine formulations. Mucosal vaccination in particular will likely be needed to induce robust immunity

Item Type: Thesis (Doctoral)
Subjects: QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination
WC Communicable Diseases > WC 20 Research (General)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 204 Pneumococcal pneumonia. Staphylococcal pneumonia
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Item titleItem URI
Influence of sex, season and environmental air quality on experimental human pneumococcal carriage acquisition
Streptococcus pneumoniae colonisation associates with impaired adaptive immune responses against SARS-CoV-2
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Depositing User: Lynn Roberts-Maloney
Date Deposited: 20 Sep 2022 10:07
Last Modified: 20 Dec 2022 02:02


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