LACTIN-V

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LACTIN-V
Clinical data
Other namesCTV-05
Lactobacillus crispatus CTV-05
Legal status
Legal status
  • Investigational
Identifiers
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] 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]

Related Research Articles

Bacterial vaginosis Excessive growth of bacteria in the vagina

Bacterial vaginosis (BV) is a disease 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.

Urinary tract infection Infection that affects part of the urinary tract

A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidney infection (pyelonephritis). Symptoms from a lower urinary tract infection include pain with urination, frequent urination, and feeling the need to urinate despite having an empty bladder. Symptoms of a kidney infection include fever and flank pain usually in addition to the symptoms of a lower UTI. Rarely the urine may appear bloody. In the very old and the very young, symptoms may be vague or non-specific.

Human microbiome Microorganisms in or on human skin and biofluids

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.

<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.

Probiotic Microorganisms said to provide health benefits when consumed

Probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut flora. Probiotics are considered generally safe to consume, but may cause bacteria-host interactions and unwanted side effects in rare cases. There is some evidence that probiotics are beneficial for some conditions, but there is little evidence for many of the health benefits claimed for them.

<i>Lactobacillus acidophilus</i> Species of bacterium

Lactobacillus acidophilus is a species of Gram-positive bacteria in the genus Lactobacillus. L. acidophilus is a homofermentative, microaerophilic species, fermenting sugars into lactic acid, and grows readily at rather low pH values and has an optimum growth temperature of around 37 °C (99 °F). L. acidophilus is found in the human and animal gastrointestinal tract and mouth. Some strains of L. acidophilus may be considered to have probiotic characteristics. These strains are commercially used in many dairy products, sometimes together with Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus in the production of acidophilus-type yogurt, or acidophiline. Its genome has been sequenced.

<i>Lacticaseibacillus rhamnosus</i> Species of bacterium

Lacticaseibacillus rhamnosus is a bacterium that originally was considered to be a subspecies of L. casei, but genetic research found it to be a separate species in the L. casei clade, which also includes L. paracasei and L. zeae. It is a short Gram-positive homofermentative facultative anaerobic non-spore-forming rod that often appears in chains. Some strains of L. rhamnosus bacteria are being used as probiotics, and are particularly useful in treating infections of the female urogenital tract, most particularly very difficult to treat cases of bacterial vaginosis. The species Lacticaseibacillus rhamnosus and Limosilactobacillus reuteri are commonly found in the healthy female genito-urinary tract and are helpful to regain control of dysbiotic bacterial overgrowth during an active infection. L. rhamnosus sometimes is used in dairy products such as fermented milk and as non-starter-lactic acid bacterium (NSLAB) in long-ripened cheese. While frequently considered a beneficial organism, L. rhamnosus may not be as beneficial to certain subsets of the population; in rare circumstances, especially those primarily involving weakened immune system or infants, it may cause endocarditis. Despite the rare infections caused by L. rhamnosus, the species is included in the list of bacterial species with qualified presumed safety (QPS) status of the European Food Safety Agency.

Vaginal discharge 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 (http://www.lactobacillus.ualberta.ca/, http://www.lactobacillus.uantwerpen.be/). 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.

Vaginal flora

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.

Vaginal yeast infection 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 hydrogen peroxide (H2O2) producing beneficial microbiota species located in both the vagina, through vaginal discharge, and the vertebrate gastrointestinal tract. The strain CTV-05 is used as a probiotic that can be used by premenopausal and postmenopausal women that experience recurrent urinary tract infections. It is being evaluated specifically for the prevention and treatment of bacterial vaginosis, which is characterized by the absence of Lactobacillus flora necessary to protect the host from infection.

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 normal inhabitant of the lower reproductive tract in healthy women. L. jensenii makes up 23% of vaginal microflora that is naturally occurring. It is also found on the skins of grapes at the time of their harvest. L. jensenii is sometimes used in producing fermented foods.

Lactobacillus vaccine 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.

TOL-463

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. In a small phase 2 randomized controlled trial, TOL-463 as an insert or gel achieved clinical cure rates of 50–59% against BV and 81–92% against VVC in women who had one or both conditions. It was effective and safe in the study, though it was without indication of superiority over other antifungal medications for VVC. The cure rates against BV with TOL-463 were said to be comparable to those with recently approved antibiotic treatments like single-dose oral secnidazole (58%) and single-dose metronidazole vaginal gel (41%). As of May 2019, TOL-463 is in phase 2 clinical trials for the treatment of BV and VVC. It was originated by Toltec Pharmaceuticals and is under development by the National Institute of Allergy and Infectious Diseases.

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.