Anna-Ursula Happel

Division of Immunology, Department of Pathology, Institute of Infectious Disease & Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town (UCT). 

Anna-Ursula Happel completed a M.Sc. in Molecular Medicine at the Friedrich-Alexander-University of Erlangen/Nuremberg in Germany and a PhD in Medical Virology at UCT. During her PhD, she evaluated live biotherapeutics to treat bacterial vaginosis in South African women at high risk of HIV acquisition. 

Her postdoctoral research in the Jaspan Laboratory from 2019 to 2021 focussed on the interplay between HIV, maternal and infant microbiota and infant health outcomes.

Her current work involves understanding interactions between bacterial and viral microbiota in the female genital tract and subsequent effects on risk of preterm birth in women with HIV, for which she received an EDCTP Career Development Fellowship in poverty-related diseases and child and adolescent health.

Ultimately, she aims to use her research to design microbiome-based diagnostics and biotherapeutics for women’s and infant’s health.

VaViBa- Interaction of vaginal virome and bacteriome in pregnant women living with HIV in sub-Saharan Africa and risk of preterm birth

Why is this project important? In Sub-Saharan Africa, there are over 33 million people living with HIV, of which a major proportion are women of childbearing age. Pregnant women with HIV are more likely to experience adverse birth outcomes, including preterm birth, compared to pregnant women without HIV. This substantially contributes to maternal and infant morbidity and mortality in sub-Saharan Africa. Alterations in vaginal bacterial communities have been linked to risk of preterm birth but cannot fully explain the increased risk. Yet the role of vaginal pro-and eukaryote-infecting viral communities, collectively referred to as “virome”, has not been rigorously evaluated with regards to birth outcomes. The gut virome is expanded in people with HIV and modulates their gut bacteriome; thus, we hypothesise that HIV infection in women of childbearing age leads to an expanded vaginal virome, including increased number and diversity of bacteriophages, which either directly or indirectly through alteration of the bacterial microbiota is associated with a higher preterm birth (PTB) risk in women with HIV (WLHIV).

What is the project about? This project leverages the infrastructure and rigorous metadata of an ongoing pregnancy cohort study in Khayelitsha, Cape Town, South Africa conducted by Associate Professor Heather Jaspan and Professor Clive Gray. Pregnant women with and without HIV are enrolled during pregnancy and vaginal swabs, clinical and obstetric data are collected throughout pregnancy and at delivery. 

We will: 
1) compare the composition and diversity of the vaginal virome in pregnant women to age- and parity-matched pregnant women without HIV, both with healthy birth outcomes, using shotgun metagenomic sequencing to evaluate the effect of HIV infection on the vaginal virome; 

2) identify in vivo associations between vaginal viruses associated with HIV infection and bacteriome and validate key bacterial-viral interactions in vitro;

3) compare vaginal virome diversity and composition of women with HIV experiencing preterm birth to age-, parity- and antiretroviral regimen-matched women with HIV with healthy birth outcomes to evaluate if changes in the vaginal virome are associated with PTB in WLHIV.

What will be achieved during the project? Besides addressing the above-described scientific questions, this fellowship supports Anna-Ursula’s journey to becoming an independent investigator, supported by a sound network of mentors and collaborators, thereby contributing to retaining and developing junior researchers in Sub-Saharan Africa.

Training of one African PhD student, preferably a female student to support the training of women in the field of science, will be enabled though this project, thereby contributing to capacity-building in South Africa.

The project will also contribute to establishing viral metagenomic data analysis in the country, a skill that is very rare in the Sub-Saharan setting. The data generated as part of this project will provide significant contributions to the virology community through the addition of novel complete viral genomes

Extensive stakeholder involvement will ensure that scientific findings are rigorously verified and thereafter translated into change of clinical practices.

Why is this project relevant to South Africa? This project is highly relevant in South Africa where HIV prevalence among pregnant women is substantial and pregnant women with HIV experience significantly higher preterm birth risk than pregnant women without HIV. Infants born preterm experience poorer short and longer-term health outcomes, which are magnified in resource-limited settings such as South Africa. Understanding the interplay between vaginal viruses, bacteria and preterm birth relevant for developing novel diagnostics and interventions for improving preterm birth among women with HIV, and to potentially decrease infant morbidity and mortality.

What is the project’s timeline? The project is taking place from 1 July 2021 – 30 June 2024. Updates on research findings will be posted here once available.

Who is providing mentorship? Mentorship for Anna-Ursula’s Career Development Fellowship in poverty-related diseases and child and adolescent health is provided by A/Prof Heather Jaspan, a Pediatric Infectious Diseases clinician with a PhD in Molecular and Cell Biology, and member of the IDM who is also part of Pediatric Infectious Diseases and Global Health at the University of Washington; Kathleen Powis (MD, MPH, MBA), Assistant Professor of Pediatrics at Harvard Medical School and Arvind Varsani, a molecular virologist and A/Prof at Arizona State University and Honorary Research Associate at the Structural Biology Research Unit at UCT.

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