INCORPORATION BY REFERENCE TO THE SEQUENCE LISTING

The content of the text file named 21486-631001WO_ST25″ which was created on Jul. 28, 2017 and is 1.45 kilobytes in size is hereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The invention relates to immune modulation.

BACKGROUND OF THE INVENTION

Among patients with Human Immunodeficiency Virus (HIV),Candida albicansinfections continue to be a problem. Patients are plagued by persistent infections, with the oral cavity being a primary infection site. The fungiC. albicans, a natural colonizer of the human intestine, mouth, and skin, can cause conditions such as thrush: hallmarked by raised, white lesions in the mouth that cause pain. Providing patients with prophylactic antifungal chemotherapy can be suboptimal in the case of a chronic infection such as HIV. With continued prevalence of an antifungal such as fluconazole in the system,C. albicanscan develop resistance, whereby the treatment can become further challenging. Among susceptible patients, persistent infections can lead to drug resistance due to the need for recurrent therapy.

SUMMARY OF THE INVENTION

The methods and compositions of the invention provide a solution to drawbacks of previous approaches to treat and prevent fungal infections. For example, the invention features a method of reducing or preventing an infection of a bodily tissue by a fungal microorganism by contacting the tissue with a composition comprising a purifiedLactobacillus paracaseibacterium. The fungal microorganism can includeCandida albicans. The bacterium or bacterial composition is preferably not substantially disseminated to lower gastrointestinal tissue. For example, theL. paracaseineed not be ingested or is not ingested. For example, theL. paracaseiis ingested less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1% or less by weight). The composition is administered to or is applied to tissues of the oral cavity or adjacent tissues. For example, the tissues include mouth, lips, tongue, throat, or esophageal tissue. The tissue does not substantially comprise stomach or intestinal tissue.

In some examples, the fungal microorganism, e.g., pathogen, comprisesCandida albicans. For example, the fungal microorganism is resistant to fluconazole. A subject to be treated may be immunocompromised, e.g., the subject had or has an HIV infection.

TheLactobacillus paracaseiis purified. By “purified” or “substantially purified” is meant aL. paracaseibacterium that is substantially free of contaminating microorganisms or other macromolecules, e.g., polysaccharides, nucleic acids, or proteins. For example, theL. paracaseicomprises strain 28.4. The bacterium or bacterial composition is in a form suitable for administration to oral cavity tissues, e.g., composition is in the form of a cream, liquid, or ointment for spreading on oral cavity tissues or in the form of a chewing gum, whereby oral cavity tissues are contacted with the bacteria as it is liberated from the gum or dissolvable or chewable tablet as the subject sucks on or chews the composition. Other formulations include a liquid mouth wash/rinse or spray to be applied to oral cavity tissues and associated tissues.

Also within the invention is a composition comprising a purifiedLactobacillus paracaseibacterium and a gellan. For example, the composition is in the form of a cream ointment, or chewing gum or chewable tablet.

The terms “subject,” “individual,” and “patient” are used interchangeably herein to refer to a vertebrate, preferably a mammal, more preferably a human. The mammal can be e.g., a human or appropriate non-human mammal, such as primate, mouse, rat, dog, cat, cow, horse, goat, camel, sheep or a pig. The subject can also be a bird or fowl. Tissues, cells and their progeny of a biological entity obtained in vivo or cultured in vitro are also encompassed. As used herein, a “subject in need thereof” or “a patient” may be a subject having a HIV or a subject who had HIV. Alternatively, a subject may be a subject comprises a fungal pathogen that is resistant to an antifungal agent (other than the composition described herein), such as fluconazole.

As used herein, “treatment” or “treating,” or “palliating” or “ameliorating” or “reducing” are used interchangeably herein. These terms refer to an approach for obtaining beneficial or desired results including but not limited to therapeutic benefit and/or a prophylactic benefit. By therapeutic benefit is meant eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit is achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the patient, notwithstanding that the patient may still be afflicted with the underlying disorder. For prophylactic benefit, the compositions may be administered to a patient at risk of developing a particular disease, or to a patient reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease may not have been made. Treatment includes preventing the disease, that is, causing the clinical symptoms of the disease not to develop by administration of a protective composition prior to the induction of the disease; suppressing the disease, that is, causing the clinical symptoms of the disease not to develop by administration of a protective composition after the inductive event but prior to the clinical appearance or reappearance of the disease; inhibiting the disease, that is, arresting the development of clinical symptoms by administration of a protective composition after their initial appearance; preventing re-occurring of the disease and/or relieving the disease, that is, causing the regression of clinical symptoms by administration of a protective composition after their initial appearance.

The term “lower gastrointestinal tissue” includes the lower gastrointestinal tract such as most of the small intestine and all of the large intestine. The gastrointestinal (GI) tract is conventionally divided into upper (mouth to ileum) and lower (cecum to anus). The lower digestive tract, also known as the bowel, is approximately 25 feet long and encompasses or consists of the small intestine and large intestine. Food from the stomach passes through the pyloric valve into the small intestine, a 20-foot tube with three sections: the duodenum, the jejunum, and the ileum. In some clinical contexts, e.g., gastrointestinal bleeding, the demarcation between the upper and lower GI tract is the duodenojejunal (DJ) junction (ligament of Treitz

All publications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

