Supervisory team
LSHTM
- Associate Professor Chris Smith (christopher.smith@lshtm.ac.uk), Profile page
- Advisor - Prof Stefan Flasche (stefan.flasche@lshtm.ac.uk), Profile page
Nagasaki University
- Lead: Associate Prof Bhim Gopal Dhoubhadel (b-gopal@nagasaki-u.ac.jp), Profile page
Project
Background
Streptococcus pneumoniae (pneumococcus) is a major cause of pneumonia in children. Although the impact of pneumococcal conjugate vaccines on pneumococcal diseases has been observed, the emergence of non-vaccine serotypes along with increasing antibiotic resistance among these non-vaccine serotypes pose a global threat to the control and prevention of pneumococcal disease (Lo SW, Lancet Infect Dis 2019; Ouldali N, Lancet Infect Dis 2020). As the nasopharyngeal colonization is the precursor of the pneumococcal diseases, the prevalence of residual vaccine serotypes and non-vaccine serotypes after years of introduction of 10- and 13-valent pneumococcal conjugate vaccine (PCV10, PCV13) is important to assess the potential use of catch up vaccine campaign and to assess the impact of newer 15- or 20-valent vaccines (PCV15, PCV20), respectively.
An observational serosurveillance study in Malawi shows the waning of antibody levels induced by PCV13 using a 3+0 schedule after the first year of life (Swarthout TD, Lancet Infect Dis 2022). The study shows post-vaccine antibody concentrations dropped below the putative correlate of protection (CoP) for carriage for several vaccine serotypes that may have contribute to the persistent vaccine-serotype carriage. Serotype specific CoP for carriage has been calculated by using serum immunoglobin G (IgG); however, effector molecules for the protection against carriage is unlikely to be circulating serum IgG (Voysey M, Clin Infect Dis 2018). Therefore, serosurveillance studies are needed to see whether we can use saliva IgG for assessment of CoP for carriage.
Proposed project
This study will involve carriage surveillance of residual vaccine serotypes and non-vaccine serotypes after years of implementation of pneumococcal vaccines (PCV10 and PCV13) in different schedules (2+1 PCV10 in Nepal, 3+0 PCV13 in DRC, and 3+1 PCV13 in Japan). Besides, the study also incorporates the serosurveillance of antibody levels (IgG) in serum and saliva at different time points of completion of vaccination.
Impact
The proposed project is expected to compare the residual vaccine serotypes in low- and high- income settings with different vaccines schedules and assess the potential need of additional booster dose of the vaccines besides present schedule. Identification of circulating non-PCV13 vaccine serotypes can provide the potential impact of newer PCV15 and PCV20 vaccines, which will help to choose appropriate vaccine for the upgrade. And antibody serveillnace against all vaccine serotypes in serum and saliva of vaccinated children with different age may provide the putative CoP against carriage based on serum IgG and saliva IgG, which may help to assess the effectiveness of pneumococcal vaccines for carriage and non-invasive diseases in the future.
The role of LSHTM and NU in this collaborative project
NU will provide the candidate opportunities to carry out clinical research in Nagasaki, including laboratory work (nanofluidic real-time PCR for molecular serotyping and Luminex multiplex system for quantification of IgG) as well as research field sites. LSHTM will provide relevant academic courses. Project supervisors in NU and LSHTM will facilitate connections and collaborations for the candidate with relevant faculties in both schools to nurture the multifaceted academic skills of the candidate.
Particular prior educational requirements for a student undertaking this project
- Medical doctor or MSc (tropical medicine or microbiology).
Skills we expect a student to develop/acquire whilst pursuing this project
- Laboratory skills in molecular serotyping and quantification of antibody
- Skills on data management and statistical analysis
- Academic writing for publication and PhD thesis