Determining the role of vaginal microbiota metabolites in activating HIV and other STIs, and their immune modulatory effects on cells found in the lower female reproductive tract.

Globally, almost 19 per cent of the 1.8 million new HIV infections in 2017 were in adolescent girls and young women in sub-Saharan Africa, where the virus mainly establishes infection by entry through the cervicovagina.

Women colonised with optimal cervicovaginal microbiota, typically dominated by Lactobacillus spp., are protected against HIV in contrast to women with “non-optimal” vaginal bacteria (e.g. bacterial vaginosis (BV)). Distinguishing features between women with BV vs Lactobacillus spp. dominated cervicovaginal microbiota include a dramatic increase in vaginal pH and a change in the concentrations of the vaginal microbiota metabolites, lactic acid, short chain fatty acid (SCFAs) and succinic acid.

This study aims to determine the antiviral and immune modulatory effects of these organic acid metabolites to understand their role in either helping to protect or to promote acquisition of HIV and other STIs.

Timeline

2016 – ongoing

Publications

2019

• The evolving facets of bacterial vaginosis: implications for HIV transmission.
  McKinnon LR, Achilles S, Bradshaw CS, Burgener A, Crucitti T, Fredricks DN, Jaspan HB, Kaul R, Kaushic C, Klatt N, Kwon DS, Marrazzo JM, Masson L, McClelland S, Ravel J, van de Wijgert JHHM, Vodstrcil LA, Tachedjian G
  AIDS Res Hum Retroviruses. 2019 Jan; 35(3):219-228

2018

• Anti-HIV-1 Activity of Lactic Acid in Human Cervicovaginal Fluid.
  Tyssen D, Wang YY, Hayward JA, Agius PA, DeLong K, Aldunate M, Ravel J, Moench TR, Cone RA, Tachedjian G
  mSphere. 2018 Jul; 3(4):e00055-18
• The implausible "in vivo" role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota.
  Tachedjian G, O'Hanlon DE, Ravel J
  Microbiome. 2018 Feb; 6(1):29

2017

• The role of lactic acid production by probiotic Lactobacillus species in vaginal health.
  Tachedjian G, Aldunate M, Bradshaw CS, Cone RA
  Res Microbiol. 2017 Apr; 168(9-10):782-792
• Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition.
  Hearps AC, Tyssen D, Srbinovski D, Bayigga L, Diaz DJD, Aldunate M, Cone RA, Gugasyan R, Anderson DJ, Tachedjian G
  Mucosal Immunol. 2017 Apr; 10(6):1480-1490

2015

• Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis.
  Aldunate M, Srbinovski D, Hearps AC, Latham CF, Ramsland PA, Gugasyan R, Cone RA, Tachedjian G
  Front Physiol. 2015 Jun; 6:164

2013

• Vaginal concentrations of lactic acid potently inactivate HIV.
  Aldunate M, Tyssen D, Johnson A, Zakir T, Sonza S, Moench T, Cone R, Tachedjian G
  J Antimicrob Chemother. 2013 May; 68(9):2015-25