Oral Presentation 31st Annual Lorne Proteomics Symposium 2026

The vaginal microbiome as a key contributor to genital mucosal vulnerability to HIV in South African adolescent girls and women (133649)

Andrea G Abrahams 1 2 , Nina Radzey 1 2 3 , Tariq Ganief 2 4 , Celia Mehou-Loko 1 , Hilton Humphries 5 6 7 , Pamela Mkhize 8 9 , Rushil Harryparsad 1 , Bahiah Meyer 1 , Monalisa T Manhanzva 1 , Natasha Samsunder 8 , Nadia Ahmed 10 , Quarraisha Abdool Karim 8 11 , Disebo Potloane 8 , Liam Bell 2 12 13 , Michelle Du Plessis 2 , Linda-Gail Bekker 4 10 , Jo-Ann S Passmore 1 8 14 , Heather B Jaspan 1 4 15 , Jonathan Blackburn 2 4 13 , Lindi Masson 3 4 8 16
  1. Department of Pathology, University of Cape Town, Cape Town, South Africa
  2. Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa
  3. Burnet Institute, Melbourne, VIC, Australia
  4. Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
  5. Centre for Community Based Research, Human Sciences Research Council, Pietermaritzburg, South Africa
  6. Department of Psychology, University of KwaZulu-Natal, Pietermaritzburg, South Africa
  7. School of Public Health, University of Cape Town, Cape Town, South Africa
  8. Centre for the AIDS Programme of Research in South Africa, Durban, South Africa
  9. School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg, South Africa
  10. Desmond Tutu HIV Centre, Cape Town, South Africa
  11. Department of Epidemiology, Columbia University, New York, USA
  12. Centre for Proteomic and Genomic Research , Cape Town, South Africa
  13. Distributed Platform in Omics (DIPLOMICS), Cape Town, South Africa
  14. National Health Laboratory Service, Cape Town, South Africa
  15. Seattle Children's Research Institute, Seattle, USA
  16. Central Clinical School, Monash University, Melbourne, Australia

Background: HIV remains highly prevalent in sub-Saharan Africa, especially among adolescent girls and young women (15-24 years). Although the socio-behavioural and biological factors that contribute to this risk are not fully understood, female genital tract (FGT) inflammation and reduced epithelial barrier function increase mucosal vulnerability to HIV acquisition. We evaluated the primary drivers of these mucosal changes in South African women and girls at high risk of HIV acquisition.

Methods: This cross-sectional analysis included 168 adolescent girls (14-19 years) and 83 adult women (25-35 years) in Cape Town and KwaZulu-Natal, South Africa. Vaginal swabs were analysed by data-independent acquisition mass spectrometry using a timsTOF Pro 2. Bacterial vaginosis (BV) was diagnosed by Nugent scoring and candidiasis by microscopy. Sexually transmitted infections (STIs), Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis, were diagnosed using nucleic acid amplification tests. Protein differential abundance was assessed using limma and functional analyses conducted using KEGG and UniProt Gene Ontology.

Results: A total of 7317 host and microbial proteins were detected. No statistically significant differences in FGT metaproteomic profiles were identified between adolescents and adults. Of the STIs evaluated, only T. vaginalis (n=19) was associated with significant host proteome changes, with 37 overexpressed and 81 underexpressed proteins. Overexpressed proteins mapped to immune pathways such as neutrophil extracellular trap formation (FDR adj. p=1.2x10-9). Candidiasis was associated with overexpression of only five host proteins. However, 231 proteins were significantly overexpressed and 539 underexpressed in BV-positive (n=111) versus negative women and girls (n=88). Overexpressed proteins mapped to inflammatory pathways including neutrophil degranulation (adj. p=2.9x10-5) and NF-kB activation (adj. p=2.4x10-4). Underexpressed proteins mapped to epithelial barrier functions including adherens junction (adj. p=0.0011) and cadherin binding (adj. p=8.14x10-7). BV-negative women had greater abundance of Lactobacillus proteins, while proteins produced by non-optimal Gardnerella and Prevotella species were more abundant in BV-positive women. A total of 418 microbial biological processes were differentially expressed in BV-positive versus negative women, including higher glucose metabolic process (adj. p=4.12x10-34) and killing of cells of another organism (adj. p=3.82x10-18). Lipoteichoic acid biosynthesis (adj. p=3.31x10-12) and peptidoglycan biosynthesis (adj. p=2.98x10-10), previously associated with low inflammation, were overexpressed in BV-negative women.

Conclusion: Substantial alterations in host inflammatory pathways and epithelial barrier dysfunction associated with potential HIV acquisition risk were observed in women and girls with BV. Future studies of these microbiome-host interactions in larger longitudinal cohorts with HIV outcomes may confirm specific targets to reduce mucosal HIV susceptibility.