Methicillin-Resistant Staphylococcus aureus (MRSA) is an antibiotic-resistant pathogen that represents a significant threat to public health. It is listed as a “High” priority pathogen on the WHO’s first ever list of antibiotic-resistant pathogens published in February, 2017. MRSA can cause severe skin lesions and can ultimately be life-threatening upon systemic invasion. The pace of resistance exhibited by MRSA has severely limited treatment options at present.
Conventional vaccine preparation methods involve antigen denaturation to minimize toxicity, but the denaturation techniques unavoidably compromise the antigenic information, causing a tradeoff between vaccine safety and efficacy. Using the unique red blood cell membrane coated nanosponge technology, Cellics is developing safer and more effective vaccines for prevention of infectious diseases caused by MRSA. In this strategy, nanosponges are first used to sequester membrane-active toxins without altering the antigenic characteristics of the toxins. Upon interaction with the nanosponges, toxins become detained and lose their toxicity as they are precluded from interacting with cellular targets. The resulting nanosponge-toxin complex (namely ‘nanotoxoid’) adopts a nanoparticulate morphology that facilitates antigen presentation to the immune system. This sequestration approach using biomimetic nanotoxoids has immense immunological implications owing to its ability in enabling structurally preserved toxins for immune processing. The biomimetic nanotoxoid vaccines also retain faithful antigenic presentation while removing toxin virulence for enhanced immunity.
In mice, vaccination with nanosponge-detained staphylococcal α-hemolysin (Hla) effectively triggers MRSA-specific immune response. Compared to mice vaccinated with control samples, those vaccinated with the nanotoxoid show superior protective immunity against MRSA skin infection. The vaccination not only inhibits lesion formation at the site of bacterial challenge but also reduces the invasiveness of MRSA, preventing dissemination into other organs.
Schematic preparation of ‘nanotoxoid’ from ‘nanosponges’. The nanotoxoid consists of substrate-supported cell membranes into which various threat agents can spontaneously incorporate.