Antibodies targeted to fungal cell wall polysaccharides

Abstract

A compound comprising one or more polysaccharide moieties each independently represented by the formula β(1→4)-[GlcNH—R]n-2,5-anhydromannose, wherein n is a positive integer from 3 to 500, and R is H or an acyl group, is described. The compound can be manufactured by (a) reacting chitosan with an acylating agent sufficient to partially N-acylate the chitosan, yielding a modified chitin / chitosan mixed polymer; and (b) reacting the modified chitin / chitosan mixed polymer with a deaminating agent to cleave the mixed polymer at the unacylated chitosan moieties. The compound can be used to immunize against fungal infection. Antibodies specific to the compound, and the use of such antibodies to protect against fungal infection are also described.

Description

BACKGROUND OF THE INVENTION[0001]A dramatic rise in the incidence of invasive fungal disease in recent years, as well as the emergence of drug resistant and previously rare fungal species, has highlighted the need for broadly effective new therapeutic and prophylactic antifungal treatment strategies (3-5). The increased incidence of invasive fungal infection is partly attributable to an increase in the immunocompromised patient population, owing to the growing number of patients with disease associated acquired immunodeficiencies, those in critical care units, patients undergoing surgery or immunosuppressive treatment, and those receiving organ or cellular transplant therapies. Importantly, the risk factors that predispose individuals to invasive fungal disease do not preclude the possibility of mounting an effective immune response and responding favorably to immunotherapy (6, 7), giving promise to the development of effective vaccine or immunotherapy based approaches to meet this ...

AI Technical Summary

Benefits of technology

The invention provides a new compound that can be used to treat fungal infections or diseases. This compound has multiple polysaccharide moieties that are joined together in a specific way. The invention also describes a process for making the compound and a method of using it to immunize mammals against fungal infections or pathogens. The compound can be administered to mammals in a safe and effective way. Additionally, the invention provides an antibody specific to the compound, which can also be used to protect mammals from fungal infections.

Problems solved by technology

Candida species are the fourth leading cause of nosocomial sepsis cases in the US and the rising incidence of invasive fungal disease from all pathogenic fungi represents a significant healthcare burden worldwide.

A global problem, worldwide, approximately 1 million new cases of cryptococcal meningitis occur each year, resulting in 625,000 deaths.

Although the widespread availability of antiretroviral therapy (ART) in developed countries has helped reduce cryptococcal infections in these areas, it is still a major problem in developing countries where access to healthcare is limited.

Nevertheless, the production of effective vaccine responses requires careful consideration of the fine structure of the target antigens, as there is mounting evidence that one mechanism of immune evasion employed by fungal pathogens is the expression of immunodominant epitopes that induce non-protective or inhibitory antibody responses.

Methods available in the art for degrading chitin into soluble fragments are not stoichiometrically controlled and it is thus difficult to modulate the degree of depolymerization.

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