A Vaccine and Monoclonal Antibodies That Enhance Mouse Resistance toCandida albicansVaginal Infection

Abstract

We previously reported that a vaccine composed of liposome-mannan complexes of Candida albicans (L-mann) stimulates mice to produce protective antibodies against disseminated candidiasis. An immunoglobulin M (IgM) monoclonal antibody (MAb), B6.1, specific for a β-1,2-mannotriose in the complexes protects against the disease, whereas MAb B6 does not. In the present study, the vaccine and MAbs B6.1 and B6 were tested for the ability to protect againstCandida vaginal infection, established by intravaginal (i.vg.) inoculation of yeast cells in mice maintained in pseudoestrus. Fungal CFU in each vagina was determined to assess the severity of infection. Mice vaccinated before infection developed about 62% fewer vaginal CFU than nonimmunized controls. Naive mice that received polyclonal antiserum (from vaccinated mice) i.vg. before infection had 60% fewer CFU than controls. The serum protective factor was stable at 56°C, but C. albicans cells absorbed this factor. Mice given MAb B6.1 i.vg. after infection was established had fewerCandida CFU in vaginal tissue than control mice given buffer instead of antibody. MAbs B6.1 and B6 given intraperitoneally before infection protected mice, but MAbs preabsorbed with yeast cells did not. MAb B6.1 also protected against C. tropicalisvaginal infection, but MAb B6 did not. The protective activities of MAbs B6.1 and B6 appeared to be specific because an irrelevant IgM carbohydrate-specific MAb and an irrelevant IgG protein-specific MAb were not protective; also, MAb B6.1 did not affect development of vaginal chlamydial infection. These studies show that an appropriate antibody response, or administration of protective antibodies, can help the host to resist Candida vaginal infection.

Mannose‐binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis

“…*Student's t test: normal women versus study subjects, P , 0.001. and none of which leading to clinical applications at this time. 26,27 Despite the accumulation of knowledge we have of underlying risk factors, we are still not able to cure or improve most women with RVC. During the last years, it has become increasingly clear that responses of different individuals to any given microorganism show considerable variability.…”

Existence of novel β‐1,2 linkage‐containing side chain in the mannan of Candida lusitaniae, antigenically related to Candida albicans serotype A

“…We have reported the presence of three kinds of b-1,2 linkage-containing side chains in the mannans from Candida species [11][12][13][14][15][16][17]. Because the b-1,2-linked mannose unit is present among the pathogenic fungi only in the mannan of the genus Candida and the b-1,2 linkage-containing side chains behave as strong antigens, many workers [18][19][20][21][22][23][24][25] have produced monoclonal antibodies to b-1,2-linked mannose units to protect against candidiasis, for the serodiagnosis of candidiasis, or for the identification of mechanisms of Candida infection. Furthermore, studies have indicated the b-1,2-linked mannose units participate in the adherence of Candida cells to mammalian cells as the first step in infection [26][27][28].…”

Emerging drugs and vaccines for Candidemia

“…111 MAb B6.1 MAb B6.1 was a prophylactic and therapeutic IgMmonoclonal antibody that specifically targeted (1?2)b-mannotriose; it was formerly under development by LigoCyte Pharmaceuticals (Deerfield, IL, USA). [117][118][119][120][121][122] (1?2)-b-mannotriose is an acid-labile component of the phospholipomannan complex, expressed uniformly on the surface of C. albicans and other pathogenic nonalbicans Candida species, which displays adhesion. 117,118,120,121,123,124 The vaccine facilitates opsonophagocytic killing via the classical pathway of the complement system.…”