2025-26 Project (LeDoare & Groppelli & Sanchez Clemente)

Mpox in Uganda: establishing existing immunity and characterising the immunological response to vaccination in pregnant women

SUPERVISORY TEAM

Supervisor

Prof Kirsty Le Doare at City St George’s
Email: kiledoar@sgul.ac.uk

Co-Supervisor

Dr Elisabetta Groppelli at City St George’s
Email: e.groppelli@sgul.ac.uk

Co-Supervisor

Dr Nuria Sanchez Clemente at City St George’s
Email: nsanchez@sgul.ac.uk

PROJECT SUMMARY

Project Summary

Mpox primarily affects rural communities in central and west Africa. However, the true seroprevalence is unknown. Pregnant women are at risk of severe complications including fetal loss. A third-generation vaccine (Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) is being rolled out by the Ministry of Health in Uganda.    

There is an urgent need to establish the existing immunological status of pregnant women and better understand the humoral immunological responses after vaccination in pregnancy, to inform vaccination policies.   

The specific objectives are to:   
1. Generate a Systematic Review on the immunological responses to orthopoxvirus vaccination and infection in pregnancy. 
2. Establish Mpox and orthopoxviruses immunity in pregnant women in Uganda by: 
a) Characterising the humoral immunological responses after natural infection and vaccination  
b) Quantifying the transfer of antibodies transplacentally and postnatally in breast milk. 
3. Assess the use of dried blood spot cards for serology as alternative to venepuncture in resource-limited settings.

Project Key Words

Mpox, maternal vaccination, Uganda, neglected tropical

MRC LID Themes

  1. Global Health
  2. Infectious Disease

Skills

MRC Core Skills

  1. Quantitative skills
  2. Interdisciplinary skills

Skills we expect a student to develop/acquire whilst pursuing this project

1. Quantitative analytical and statistical skills, critical thinking
2. Laboratory skills: In vitro: ELISA (IgG, IgM. IgA); in cells: virus neutralisation assays using Vaccinia (BSL2) and Mpox virus (BSL3) 
3. Communication skills: scientific writing and oral presentation in scientific meetings; engagement and communication with affected communities, ministry of health and other stakeholders

Routes

Which route/s are available with this project?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • City St George’s – MRes Biomedical Science – Infection and Immunity

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? No

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training (for research degree study). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: City St George’s, London

Travel requirements for this project: None

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • Minimum City St George’s institutional eligibility criteria for doctoral study.
  • BSc/MSc (or equivalent) in related field

Other useful information

  • Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

Mpox, caused by the monkeypox virus, has affected rural communities in Central and West Africa for decades. Although cases often present with a widespread pustular rash, a proportion of cases are thought to be mild or asymptomatic. Therefore,  the true mpox seroprevalence is unknown and there is an urgent need to establish the existing immunological status of at-risk populations, including pregnant women, to better understand viral circulation and to inform vaccination policies. 

The Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine is recommended against mpox by WHO and is being rolled out by the Ministry of Health in Uganda. However, MVA-BN is not licensed for use in pregnant women, despite being at risk of severe complications including fetal loss, as they have not been included in any vaccine studies to date. Therefore, the supervisory team is currently designing maternal MVA-BN vaccine safety and reactogenicity studies in Uganda. This project aims to complement those studies by characterising the humoral immunological responses to vaccination in pregnant women, to inform vaccination policies and future vaccine development.   

Project objectives: 
1. Generate a Systematic Review on the immunological responses to orthopoxvirus vaccination and infection in pregnancy. 
2. Chraracterise Mpox and orthopoxviruses immunity in a cohort of pregnant women in Uganda by: 
a) Assessing the humoral immunological responses before and after vaccination;  
b) Quantifying the transfer of antibodies transplacentally and postnatally in breast milk. 
3. Assess the use of dried blood spot cards for serology as alternative to venepuncture in resource-limited settings.   

Techniques to be used: 
The project will start with a systematic review and meta-analysis on the serological responses to orthopoxviruses vaccination and infection in pregnancy accordance with PRISMA guidelines. This will focus on humoral immunity in samples relevant to maternal and child health (serum, plasma, human milk, vaginal fluid, cord blood).    

The student will then develop the laboratory component aimed at establishing the humoral immunological responses to MVA-BN in a cohort of pregnant women in Uganda. Antibodies (IgG, IgM, IgA) titres and neutralisation power will be assessed with ELISA and plaque reduction neutralisation test (PRNT), using MPXV (BSL3) and vaccine strain (MVA-BN; BSL2). Transfer of antibodies to the fetus transplacentally and postnatally in breast milk will also be quantified.   Finally, the student will evaluate the use of dried blood spot (DBS) cards as an alternative to venepuncture for immunological assays.    

Confirmed availability of specialist materials: 
All regents required for this project are available commercially or from the research community.  
Samples (including blood; sera) will be obtained from ongoing studies led by Professor Kirsty Le Doare.    

Potential risks and their mitigation: 
The supervisory team is currently designing maternal mpox vaccine safety and reactogenicity studies to coincide with the Ministry of Health vaccine roll out in Uganda. We anticipate to use these samples as with previous similar studies. Laboratory-based assays carry inherent risks like shortages of reagents due to high global demand. We will mitigate this by engaging directly with suppliers and planning their purchase in a timely manner.

Further reading

Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

LeDoare-Groppelli-SanchezClemente recording

MRC LID LINKS

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