Efungumab and caspofungin: pre-clinical data supporting synergy.

Objectives: Heat shock protein 90 (hsp90) is targeted by the humoral response in invasive candidiasis. This paper tests for synergy between caspofungin and efungumab--a human antibody fragment against hsp90.

Methods: The MIC-0, MIC-2 values and FICI were determined for a range of yeasts against efungumab and caspofungin.

Fungal heat-shock proteins in human disease.

Heat-shock proteins (hsps) have been identified as molecular chaperones conserved between microbes and man and grouped by their molecular mass and high degree of amino acid homology. This article reviews the major hsps of Saccharomyces cerevisiae, their interactions with trehalose, the effect of fermentation and the role of the heat-shock factor. Information derived from this model, as well as from Neurospora crassa and Achlya ambisexualis, helps in understanding the importance of hsps in the pathogenic fungi, Candida albicans, Cryptococcus neoformans, Aspergillus spp.

Preclinical assessment of the efficacy of mycograb, a human recombinant antibody against fungal HSP90.

Mycograb (NeuTec Pharma plc) is a human genetically recombinant antibody against fungal heat shock protein 90 (HSP90). Antibody to HSP90 is closely associated with recovery in patients with invasive candidiasis who are receiving amphotericin B (AMB). Using in vitro assays developed for efficacy assessment of chemotherapeutic antifungal drugs, Mycograb showed activity against a wide range of yeast species (MICs against Candida albicans [fluconazole [FLC]-sensitive and FLC-resistant strains], Candida krusei, Candida tropicalis, Candida glabrata, and Candida parapsilosis, 128 to 256 microg/ml).

Neutralising human recombinant antibodies to human cytomegalovirus glycoproteins gB and gH.

A phage antibody display library of single chain fragment variable (scFv) was applied to develop anti-HCMV glycoprotein B (gB) and glycoprotein H (gH) neutralising libraries. To enrich for specific scFvs, the phage antibody was panned against cytomegalovirus epitopes derived from the N-terminal part of gB, the C-terminal part of gB and the N-terminal part of gH (NETIYNTTLKYGDV, VTSGSTKD and AASEALDPHAFHLLLNTYGR). A number of clones were differentiated by Bst N1 fingerprinting.

Identification of ABC transporters in vancomycin-resistant Enterococcus faecium as potential targets for antibody therapy.

The occurrence of an outbreak of septicaemias due to vancomycin-resistant Enterococcus faecium (VRE), in Manchester, UK, provided an opportunity to examine the antibody responses in patients infected by the same strain. Immunoblotting sera from 24 cases, six of whom died, showed an immunodominant cluster of antigens at 34, 54 and 97 kDa, with a statistically significant correlate between survival and immunoglobulin G to the 34 and 97 kDa bands (P<0.05).