Nanoparticle‐Based Antivirulence Vaccine for the Management of Methicillin‐Resistant Staphylococcus aureus Skin Infection

Abstract

With the rising threat of antibiotic-resistant bacteria, vaccination is becoming an increasingly important strategy to prevent and manage bacterial infections. Made from deactivated bacterial toxins, toxoid vaccines are widely used in the clinic as they help to combat the virulence mechanisms employed by different pathogens. Herein, the efficacy of a biomimetic nanoparticle-based anti-virulence vaccine is examined in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) skin infection. Vaccination with nanoparticle-detained staphylococcal α-hemolysin (Hla) effectively triggers the formation of germinal centers and induces high anti-Hla titers. Compared to mice vaccinated with control samples, those vaccinated with the nanoparticle toxoid 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. Overall, this biomimetic nanoparticle-based toxin detainment strategy is a promising method for the design of potent anti-virulence vaccines for managing bacterial infections.

Cell membrane-derived nanomaterials for biomedical applications

“…A notable example involves the use of nanosponges to first neutralize bacterial toxins, enabling subsequent administration with the resulting nanoparticle-toxin complex, termed a nanotoxoid, as a safe and effective means of antivirulence vaccination [251]. This strategy has demonstrated the ability to elicit potent humoral responses against bacterial toxins, protecting mice when infected with the secreting pathogen [252]. For cancers, cell membrane-coated nanoparticles have been proposed as a platform for co-delivering multivalent tumor antigen material along with immunological adjuvants, helping to overcome some of the fundamental issues currently facing anticancer vaccine development [223].…”

Improving Vaccine and Immunotherapy Design Using Biomaterials

“…Other infectious diseases being targeted by biomaterial-based approaches include methicillin-resistant Staphylococcus aureus , where PLGA NPs are being tested to combat antibiotic resistance [48]. One candidate vaccine against Chlamydia trachomatis – a common sexually transmitted disease with no vaccine – involves pH-responsive polymers and TLRas linked to UV-inactivated C. trachomatis [49].…”

In Situ Capture of Bacterial Toxins for Antivirulence Vaccination

“…[10,11] Neutralization of these bacterial virulence factors can have a marked impact on bacteria survivability. [12] One major advantage of employing antivirulence therapy is that, unlike with antibiotics, the treatment itself doesn't exert direct selective pressure on individual bacterium; by focusing instead on blocking pathogen-to-host interactions, this strategy can ultimately translate into a reduced likelihood of developing resistance. [13] Implementation of this strategy has varied, ranging from traditional antibody neutralization [14,15] to novel nanotechnology-based complexation.…”

“…While previous versions of nanotoxoids have worked with individual, purified toxins, [12,36] the advantage of the present approach is its ability to entrap and neutralize pathogen-specific virulence factors from a protein preparation with unknown composition. To validate this concept, we probed the nanotoxoid(hSP) formulation for the presence of known virulence factors by immunoblotting (Figure 2E).…”