Nanotoxoid vaccination protects against opportunistic bacterial infections arising from immunodeficiency

Abstract

The rise in nosocomial infections caused by multidrug-resistant pathogens is a major public health concern. Patients taking immunosuppressants or chemotherapeutics are naturally more susceptible to infections. Thus, strategies for protecting immunodeficient individuals from infections are of great importance. Here, we investigate the effectiveness of a biomimetic nanotoxoid vaccine in defending animals with immunodeficiency against Pseudomonas aeruginosa . The nanotoxoids use a macrophage membrane coating to sequester and safely present bacterial virulence factors that would otherwise be too toxic to administer. Vaccination with the nanoformulation results in rapid and long-lasting immunity, protecting against lethal infections despite severe immunodeficiency. The nanovaccine can be administered through multiple routes and is effective in both pneumonia and septicemia models of infection. Mechanistically, protection is mediated by neutrophils and pathogen-specific antibodies. Overall, nanotoxoid vaccination is an attractive strategy to protect vulnerable patients and could help to mitigate the threat posed by antibiotic-resistant superbugs.

Specific interaction based drug loading strategies

“…Previous reports have shown that nanomaterials containing toxin/protein receptors can be used to remove toxins/virus. [64][65][66][67][68][69] For instance, Zhang's group coated neuronal cell membranes to PLGA nanoparticles to construct a nanosponge that specifically neutralized neurotoxins, because the neuronal cell membrane contained large amount of neurotoxin receptors (ion channel proteins). 68 They also used nanosponges rich in ACE2 to neutralize the SARS-CoV-2 virus, significantly reducing the risk of host cells being invaded by the virus.…”

Immunostimulatory DNA Hydrogel Enhances Protective Efficacy of Nanotoxoids against Bacterial Infection

“…For example, the specificity of the nanotoxoid can be altered by using a different membrane coating combined with antigenic material from other pathogens. [45,46] For the hydrogel component, various types of nucleic acid-based structures can be designed with customtailored functionality. [47,48] Continued research along these lines will yield new platforms with unique features that can be used to help address a wide range of important human health conditions.…”

Subunit vaccines for Acinetobacter baumannii

“…A. baumannii bloodstream infection probably causes bacterial endocarditis and produces bacterial valve growth. Although there was no study has examined the pathology of endocarditis, studies indicate that the heart bacterial load in the immunized group was significantly lower than that in the non-immunized group (143,176). Therefore, selection of indicators based on different infection model is of great significance for the comprehensive evaluation of the protective efficacy of the vaccine.…”