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Principal Investigator: Susan Anne Tuddenham
Organization: JOHNS HOPKINS UNIVERSITY
Fiscal Year: 2024
Award: $203,892
Funding agency: National Institute of Allergy and Infectious Diseases
Bacterial vaginosis (BV), which is characterized by a dysbiotic vaginal microbiota low in Lactobacillus species,
affects nearly 30% of U.S. women; the majority (55%) are asymptomatic (aBV). Guidelines currently
recommend testing and treatment only for symptomatic BV (sBV). BV (a composite variable with aBV and
symptomatic BV [sBV]) has been associated with an increased risk of sexually transmitted infections (STIs)
and HIV acquisition. Although studies to distinguish the differential risk of incident STI or HIV between women
with aBV and sBV have not been published, preliminary data from our group suggests that aBV is strongly
associated with incident STI and a published pilot study of BV suppressive therapy in women with aBV
indicated a decrease in chlamydia cases. To date, enthusiasm for research on or clinical treatment of aBV has
been limited, primarily by lack of data on aBV risks and perceptions of low efficacy of currently available BV
treatments. However, while BV treatment is challenging, approximately 50% of women with sBV taking
currently available therapies do achieve lasting cure. Moreover, novel, more effective therapies for BV are on
the horizon: a recent high-profile randomized trial of Lactin V, a L. crispatus intravaginal live biotherapeutic
product, showed reduced BV recurrence13. As new, better treatments for sBV become available, it is critical to
determine whether women with aBV should also be treated, in order to prevent sequelae such as STI or HIV
acquisition. If the vaginal microenvironment is shown to be identical in women with sBV and aBV, this will be
an important initial step demonstrating that aBV is a condition that should not be ignored, and will galvanize
further studies to define aBV, STI and HIV risk, and advance treatment. In a large epidemiologic study of over
300 women, our specific aims are to assess whether women with aBV and sBV differ in two broad areas (1)
biobehavioral factors and (2) the vaginal microenvironment, including factors associated with HIV and STI
acquisition risk (vaginal microbiota, key metabolites and soluble mediators of inflammation). This is a
secondary analysis leveraging existing data from a previously funded study (NIAID R01-AI116799, PI:
Brotman) for which 16S rRNA gene amplicon, metabolomic, and immunologic profiles have already been
generated from cervicovaginal lavage samples collected in the NIH's Longitudinal Study of Vaginal Flora.
Information gained through this proposed study will provide foundational data to better define aBV, and to
determine whether future studies to define the risk of HIV and STI acquisition associated with aBV, or studies
of aBV treatment as a method to prevent HIV and STIs are needed. This resubmission application is in
response to a program announcement (PAR-20-291) which is designed for Exploratory and Developmental
Research Grant Program for NIAID K-award Recipients. It will provide career development for the PI to
transition to research independence with a highly feasible and valuable clinical research project focused on the
vaginal microbiome and women's health.
Terms: <16S gene sequencing><16S rRNA amplicon sequencing><16S rRNA gene amplicon sequencing><16S rRNA gene sequencing><16S rRNA genomic profiling><16S rRNA sequencing><16S ribosomal RNA gene sequencing><16S ribosomal RNA sequencing><16S sequencing><3-10C><A vaginae><A. vaginae><AIDS Virus><AMCF-I><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Affect><Age><American><Anaerobic Bacteria><Antibiotic Therapy><Antibiotic Treatment><Area><Atopobium vaginae><Automobile Driving><B-Cell Differentiation Factor Gene><B-Cell Stimulatory Factor 2 Gene><BSF-2 Gene><BSF2 Gene><Bacteria><Bacterial Vaginitis><Bacterial Vaginosis><Behavioral><Beta Proprotein Interleukin 1><Beta-2 Gene Interferon><Biogenic Amines><Biological Response Modifier Therapy><Biological Therapy><Black><Black race><CXCL8><Career Development Awards><Career Development Awards and Programs><Career Development Programs K-Series><Chlamydia><Clinical Research><Clinical Study><Clinical Treatment><Cohort Studies><Concurrent Studies><Data><Data Bases><Data Sources><Databases><Development><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology><Epidemiology Research><Female Health><Feminine><Funding><Future><GCP1><General Taxonomy><Grant><Guidelines><HIV><HIV risk><HIV-1><HIV-I><HIV1><HSF Gene><Hepatocyte Stimulatory Factor Gene><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human immunodeficiency virus 1><Hybridoma Growth Factor Gene><Hygiene><IFN-Gamma><IFN-g><IFN-γ><IFNB2 Gene><IFNG><IFNγ><IL-1 beta><IL-1 β><IL-1-b><IL-1β><IL-6 Gene><IL-8><IL1-Beta><IL1-β><IL1B Protein><IL1F2><IL1β><IL6><IL6 gene><IL8><IL8 gene><Immune Interferon><Immunochemical Immunologic><Immunologic><Immunologic Factors><Immunological><Immunological Factors><Immunologically><Immunologics><Inflammation><Inflammation Mediators><Inflammatory><Interferon Gamma><Interferon Type II><Interleukin 1beta><Interleukin 6 (Interferon, Beta 2) Gene><Interleukin-1 beta><Interleukin-1β><Interleukin-6 Gene><Isomerism><K-Awards><K-Series Research Career Programs><K60><LAV-HTLV-III><Lactic acid><Lactobacillus><Lavage><Lead><Longitudinal Studies><Lymphadenopathy-Associated Virus><Mediating><Methods><Miyagawanella><NIAID><NIH><NIH Program Announcements><National Institute of Allergy and Infectious Disease><National Institutes of Health><Nonspecific Vaginitis><Output><Pathogenesis><Patients><Pb element><Perception><Pilot Projects><Predisposition><Preinterleukin 1 Beta><Program Announcement><Publishing><R-Series Research Projects><R01 Mechanism><R01 Program><Randomization trial><Recommendation><Recurrence><Recurrent><Reproductive Health><Research><Research Career Program><Research Grants><Research Project Grants><Research Projects><Ribosomal RNA Genes><Risk><SCYB8><Sampling><Sexually Transmitted Diseases><Sexually Transmitted Disorder><Sexually Transmitted Infection><Smoking><Susceptibility><Symptoms><TSG-1><Taxonomy><Testing><Uncertainty><United States National Institutes of Health><Vagina><Venereal Diseases><Venereal Disorders><Venereal Infections><Virus-HIV><Woman><Women's Health><adverse consequence><adverse outcome><ages><anaerobe><b-ENAP><bacterial disease treatment><bacterial infectious disease treatment><bedsonia><biobehavior><biobehavioral><biological therapeutic><biological treatment><biologically based therapeutics><biotherapeutics><biotherapy><career development><cervicovaginal><condoms><cytokine><data base><design><designing><developmental><doubt><driving><dysbacteriosis><dysbiosis><dysbiotic><effective therapy><effective treatment><epidemiologic><epidemiologic investigation><epidemiological><epidemiology study><heavy metal Pb><heavy metal lead><hormonal contraception><hormonal contraceptive><immunologic substance><immunological substance><improved><infection risk><inflammatory mediator><isomer><lFN-Gamma><lavage therapy><long-term study><longitudinal outcome studies><longterm study><metabolism measurement><metabolome><metabolomics><metabonome><metabonomics><microbial consortia><microbial flora><microbial imbalance><microbiota><microflora><multispecies consortia><non-specific vaginitis><novel><perceived stress><perception of stress><pilot study><prevent><preventing><programs><rRNA Genes><randomized trial><reproductive><response><secondary analysis><self-reported stress><sexually acquired infection><stress perception><symptom treatment><symptomatic treatment><symptomatology><treat symptom><trial regimen><trial treatment><vagina microbiota><vaginal biome><vaginal flora><vaginal microbial community><vaginal microbiome><vaginal microbiota><vaginal microflora>