Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response.

The in vitro assessment of the synergistic effects of antibiotics and wound dressings on biofilms from diabetic foot pathogens

The impact of biofilm in the effective control of wound microbiome is an ongoing dilemma which has seen the use of different treatment strategies. The effects of wound dressings and antibiotics on both planktonic bacteria and biofilms have been separately evaluated in previous studies. In this current study, the combined antimicrobial effects of some selected wound dressings (silver-impregnated: Acticoat and Silvercel; and honey-impregnated: Medihoney™ Apinate) and antibiotics (ceftazdime and levofloxacin) on Klebsiella pneumoniae and Proteus mirabilis in their quasi-biofilm state were assessed using zone of inhibition (ZOI) test. Before the addition of the wound dressings, bacterial suspension of 108 colony forming units per mL and different concentrations of ceftazidime and levofloxacin (256, 512, 1024 and 5120µg/mL) of a final volume of 1mL were inoculated on Mueller Hinton agar and allowed to dry. Wound dressings cut into circular shapes (2cm diameter) were aseptically placed on the agar plates and incubated at 35 – 37°C for 24 hours. ZOIs associated with Acticoat, Silvercel and Medihoney™ Apinate dressings were compared with that of Atrauman (non-medicated control) dressing. All three dressings showed significant (p < 0.05) biofilm-inhibiting activity against both bacteria at antibiotic concentrations of 1024 and 5120µg/mL with ZOI between 17.5 and 35mm.