LACTIN-V

Last updated
LACTIN-V
Clinical data
Other namesCTV-05; CTV05; Lactobacillus crispatus CTV-05
Legal status
Legal status
  • Investigational
Identifiers
PubChem SID
DrugBank
UNII

LACTIN-V, also known as CTV-05 or as Lactobacillus crispatus CTV-05, is a live biopharmaceutical medication containing a strain of Lactobacillus crispatus (L. crispatus) which is under development for the treatment of urinary tract infections (UTIs) and bacterial vaginosis (BV). [1] [2] It is administered intravaginally and is described as the first vaginal microbiome (VMB)-based live biotherapeutic product (LBP). [2]

Contents

Depletion of hydrogen peroxide (H2O2)-producing Lactobacillus strains such as Lactobacillus crispatus in the vagina has been strongly associated with BV and UTIs. [2] Most commercially available probiotic Lactobacillus strains are not vaginal strains and do not appear to improve vaginal or urinary health outcomes. [2] The Centers for Disease Control and Prevention (CDC)'s Sexually Transmitted Infections Treatment Guidelines (2021) noted that intravaginal LACTIN-V produced a considerably lower recurrence of BV following initial antibiotic treatment with metronidazole in a randomized controlled trial. [3] [4] However, the guidelines also noted that LACTIN-V is not yet Food and Drug Administration (FDA)-approved or commercially available. [3]

As of December 2021, LACTIN-V is in phase 2/3 clinical trials for the treatment of UTIs and is in phase 2 trials for the treatment of BV. [1] It was originated by GyneLogix and is under development by Osel Inc., the National Institute of Allergy and Infectious Diseases, and other organizations. [1]

See also

Related Research Articles

<span class="mw-page-title-main">Bacterial vaginosis</span> Excessive growth of bacteria in the vagina

Bacterial vaginosis (BV) is an infection of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urination may occur. Itching is uncommon. Occasionally, there may be no symptoms. Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS. It also increases the risk of early delivery among pregnant women.

<i>Lactobacillus</i> Genus of bacteria

Lactobacillus is a genus of gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus Lactobacillus comprised over 260 phylogenetically, ecologically, and metabolically diverse species; a taxonomic revision of the genus assigned lactobacilli to 25 genera.

<i>Gardnerella vaginalis</i> Species of bacterium

Gardnerella vaginalis is a species of Gram-variable-staining facultative anaerobic bacteria. The organisms are small non-spore-forming, nonmotile coccobacilli.

Vaginitis, also known as vulvovaginitis, is inflammation of the vagina and vulva. Symptoms may include itching, burning, pain, discharge, and a bad smell. Certain types of vaginitis may result in complications during pregnancy.

<span class="mw-page-title-main">Vaginal discharge</span> Medical condition

Vaginal discharge is a mixture of liquid, cells, and bacteria that lubricate and protect the vagina. This mixture is constantly produced by the cells of the vagina and cervix, and it exits the body through the vaginal opening. The composition, amount, and quality of discharge varies between individuals and can vary throughout the menstrual cycle and throughout the stages of sexual and reproductive development. Normal vaginal discharge may have a thin, watery consistency or a thick, sticky consistency, and it may be clear or white in color. Normal vaginal discharge may be large in volume but typically does not have a strong odor, nor is it typically associated with itching or pain. While most discharge is considered physiologic or represents normal functioning of the body, some changes in discharge can reflect infection or other pathological processes. Infections that may cause changes in vaginal discharge include vaginal yeast infections, bacterial vaginosis, and sexually transmitted infections. The characteristics of abnormal vaginal discharge vary depending on the cause, but common features include a change in color, a foul odor, and associated symptoms such as itching, burning, pelvic pain, or pain during sexual intercourse.

Levilactobacillus brevis is a gram-positive, rod shaped species of lactic acid bacteria which is heterofermentative, creating CO2, lactic acid and acetic acid or ethanol during fermentation. L. brevis is the type species of the genus Levilactobacillus (previously L. brevis group), which comprises 24 species. It can be found in many different environments, such as fermented foods, and as normal microbiota. L. brevis is found in food such as sauerkraut and pickles. It is also one of the most common causes of beer spoilage. Ingestion has been shown to improve human immune function, and it has been patented several times. Normal gut microbiota L. brevis is found in human intestines, vagina, and feces.

<span class="mw-page-title-main">Vaginal flora</span> Microorganisms present in the vagina

Vaginal flora, vaginal microbiota or vaginal microbiome are the microorganisms that colonize the vagina. They were discovered by the German gynecologist Albert Döderlein in 1892 and are part of the overall human flora. The amount and type of bacteria present have significant implications for an individual's overall health. The primary colonizing bacteria of a healthy individual are of the genus Lactobacillus, such as L. crispatus, and the lactic acid they produce is thought to protect against infection by pathogenic species.

Prevotella is a genus of Gram-negative bacteria.

<span class="mw-page-title-main">Vaginal yeast infection</span> Medical condition

Vaginal yeast infection, also known as candidal vulvovaginitis and vaginal thrush, is excessive growth of yeast in the vagina that results in irritation. The most common symptom is vaginal itching, which may be severe. Other symptoms include burning with urination, a thick, white vaginal discharge that typically does not smell bad, pain during sex, and redness around the vagina. Symptoms often worsen just before a woman's period.

Lactobacillus crispatus is a common, rod-shaped species of genus Lactobacillus and is a lactic acid producing bacterial species located in both the vagina, through vaginal discharge, and the vertebrate gastrointestinal tract. This species commonly found in vaginal microbiome and is thought to be beneficial to health.

The vaginal flora in pregnancy, or vaginal microbiota in pregnancy, is different from the vaginal flora before sexual maturity, during reproductive years, and after menopause. A description of the vaginal flora of pregnant women who are immunocompromised is not covered in this article. The composition of the vaginal flora significantly differs in pregnancy. Bacteria or viruses that are infectious most often have no symptoms.

Lactobacillus jensenii is a lactic acid bacteria species in the genus Lactobacillus.

The Human Microbiome Project (HMP), completed in 2012, laid the foundation for further investigation into the role the microbiome plays in overall health and disease. One area of particular interest is the role which delivery mode plays in the development of the infant/neonate microbiome and what potential implications this may have long term. It has been found that infants born via vaginal delivery have microbiomes closely mirroring that of the mother's vaginal microbiome, whereas those born via cesarean section tend to resemble that of the mother's skin. One notable study from 2010 illustrated an abundance of Lactobacillus and other typical vaginal genera in stool samples of infants born via vaginal delivery and an abundance of Staphylococcus and Corynebacterium, commonly found on the skin surfaces, in stool samples of infants born via cesarean section. From these discoveries came the concept of vaginal seeding, also known as microbirthing, which is a procedure whereby vaginal fluids are applied to a new-born child delivered by caesarean section. The idea of vaginal seeding was explored in 2015 after Maria Gloria Dominguez-Bello discovered that birth by caesarean section significantly altered the newborn child's microbiome compared to that of natural birth. The purpose of the technique is to recreate the natural transfer of bacteria that the baby gets during a vaginal birth. It involves placing swabs in the mother's vagina, and then wiping them onto the baby's face, mouth, eyes and skin. Due to the long-drawn nature of studying the impact of vaginal seeding, there are a limited number of studies available that support or refute its use. The evidence suggests that applying microbes from the mother's vaginal canal to the baby after cesarean section may aid in the partial restoration of the infant's natural gut microbiome with an increased likelihood of pathogenic infection to the child via vertical transmission.

<span class="mw-page-title-main">Lactobacillus vaccine</span> Vaccine using an inactivated strain of Lactobacillus

Lactobacillus vaccines are used in the therapy and prophylaxis of non-specific bacterial vaginitis and trichomoniasis. The vaccines consist of specific inactivated strains of Lactobacilli, called "aberrant" strains in the relevant literature dating from the 1980s. These strains were isolated from the vaginal secretions of patients with acute colpitis. The lactobacilli in question are polymorphic, often shortened or coccoid in shape and do not produce an acidic, anti-pathogenic vaginal environment. A colonization with aberrant lactobacilli has been associated with an increased susceptibility to vaginal infections and a high rate of relapse following antimicrobial treatment. Intramuscular administration of inactivated aberrant lactobacilli provokes a humoral immune response. The production of specific antibodies both in serum and in the vaginal secretion has been demonstrated. As a result of the immune stimulation, the abnormal lactobacilli are inhibited, the population of normal, rod-shaped lactobacilli can grow and exert its defense functions against pathogenic microorganisms.

<span class="mw-page-title-main">TOL-463</span> Combination drug

TOL-463 is an anti-infective medication which is under development for the treatment of bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). It is a boric acid-based vaginal anti-infective enhanced with ethylenediaminetetraacetic acid (EDTA) which was designed to have improved activity against vaginal bacterial and fungal biofilms while sparing protective lactobacilli. EDTA enhances the antimicrobial activity of boric acid and improves its efficacy against relevant biofilms.

Uromune, also known by its developmental code name MV-140, is a polyvalent bacterial vaccine which is used and is being developed for prevention of recurrent urinary tract infections (UTIs). In clinical studies, it has been found to reduce total number of UTIs by about 70%, to increase UTI-free rates from around 25% to 57%, and to increase time to next UTI from about 1.6 months to 9.0 months. It has also been found to reduce subjective UTI symptoms, reduce antibiotic use, and improve quality of life. The effectiveness of the vaccine appears to decrease with time, which might warrant readministration. Uromune is used as a sublingual spray once daily for 3 months.

A UTI vaccine is a vaccine used for prevention of recurrent urinary tract infections (UTIs). A number of UTI vaccines have been developed and/or marketed. These include Uromune, UroVaxom, Solco-Urovac, ExPEC4V, and SEQ-400.

References

  1. 1 2 3 "CTV 05". Adis Insight.
  2. 1 2 3 4 Lagenaur LA, Hemmerling A, Chiu C, Miller S, Lee PP, Cohen CR, Parks TP (June 2021). "Connecting the Dots: Translating the Vaginal Microbiome Into a Drug". J Infect Dis. 223 (12 Suppl 2): S296–S306. doi:10.1093/infdis/jiaa676. PMC   8502429 . PMID   33330916.
  3. 1 2 "Bacterial Vaginosis - STI Treatment Guidelines". www.cdc.gov. July 19, 2021.
  4. Cohen CR, Wierzbicki MR, French AL, Morris S, Newmann S, Reno H, Green L, Miller S, Powell J, Parks T, Hemmerling A (May 2020). "Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis". N Engl J Med. 382 (20): 1906–1915. doi:10.1056/NEJMoa1915254. PMC   7362958 . PMID   32402161.