Vaginal microbiome dysbiosis and sexually transmitted infections correlate with concentrations of immunoglobulin isotypes in human cervicovaginal mucus: Insights into HIV-1 transmission

Matrona Mbendo Akiso^1,2Israel Onyango Abook¹Marianne W Mureithi^1,2Janet Kemunto Kombo^1,2Print Koi¹Joel Awita Musando²Ruth Jeruto Chirchir²Michael D McRaven³Ann Marie Carias³Sarah Joseph⁴Omu Anzala^1,2Thomas J. Hope^3*

• ¹Department of Medical Microbiology and Immunology, Faculty of Health Sciences, University of Nairobi, Nairobi, Kenya
• ²KAVI – Institute of Clinical Research, Faculty of Health Sciences, University of Nairobi, Nairobi, Kenya
• ³Feinberg School of Medicine, Cell and Developmental Biology Department, Northwestern University, Chicago, United States
• ⁴Department of Infectious Disease - Faculty of Medicine, Imperial College London, London, United Kingdom

Little is known about relationships between antibody isotype in CVM and local microenvironment and how this impacts HIV-1 transmission at the female genital mucosa. In a cohort of 139 adult women in Kenya, we measured antibody isotypes in CVM and describe their associations with local pH, serum concentrations of oestrogen and progesterone, and sexually transmitted infections (STIs), including HIV-1. We found that IgG2 was the most abundant and IgG4 the least abundant in the CVM. Overall, IgG1 concentrations were significantly lower in CVM samples from women with BV compared to those without BV. Among women with BV, IgG1 concentrations declined further as vaginal pH increased, suggesting possible pH-mediated degradation. We also report negative associations of BV status with IgG3 and IgG4. In addition, infection with Mycoplasma genitalium and Neisseria gonorrhoeae was positively associated with concentrations of IgA and IgM, respectively. We also found relationships of antibody isotype and subclasses with HIV-1 viral mobility in vitro. IgG3 concentrations negatively correlated with CAP045 HIV-1 mobility and IgG1 concentrations negatively correlated to the mobility of the 92TH023 recombinant HIV-1 strain upon VRC01 depletion. These observations point towards a potentially protective role for IgG1 and IgG3 in trapping certain HIV-1 strains in the CVM. Importantly, our study builds on previous work, providing a potential mechanism by which BV and STIs may modulate immunoglobulin isotype and subclass content in the CVM. These results highlight the need for proper treatment of BV and other STIs, as this could impact the effectiveness of HIV-1 vaccines targeted at enhancing specific immunoglobulin responses in the cervicovaginal mucosa.