Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance

La Guidara, Chiara; Adamo, Roberto; Sala, Claudia; Micoli, Francesca

doi:10.3390/ijms25105487

Cited by 6 publications

(1 citation statement)

References 159 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This could be a game changer for managing wound infections in military situations if fully exploited [45]. While most of the studies emphasized Vaccines and monoclonal antibodies can be exploited to prevent and treat diseases caused by AMR pathogens, thereby reducing antibiotic use and decreasing selective pressure that favours the emergence of resistant strains [46][47][48]. In the course of war, managing wound infections in soldiers presents a challenge owing to antibiotic resistance.…”

Section: Discussionmentioning

confidence: 99%

The use of immunological drugs for the treatment of wound infections in military personnel during hostilities

2024

Педагогічна Академія: Наукові Записки

View full text Add to dashboard Cite

Aims: To assesses the trends in immunological drug development for managing wound infections in military personnel. To discuss the efficacy, safety, and long-term results, focusing on combination therapies, and identifying research deficits for improving the care of military wounds. Methodology: A narrative review was used in order to explores the use of immunological drugs for treating wound infections in military settings utilising a search strategy identified 840 publications from PubMed, with 6 studies meeting inclusion criteria for analysis from the years 2019 to 2022. Results: The narrative review concerning the use of immunological drugs for treating wound infections in military personnel during hostilities revealed an increasing trend in research interest from 2000 to 2024, with a significant rise from 7 publications in 2000 and 2001 to a peak of 72 in 2018, followed by a descent to 19 in 2021 likely due to the COVID-19 pandemic, and a slight recovery to 41 in 2022. The key findings included a 50% reduction in infection rates and a 30% faster healing time with monoclonal antibody treatments, over 95% accuracy in species identification of MDR strains, and reduced bacteremia incidence with GM-CSF and G-CSF. Adverse effects varied from mild to moderate, including infusion reactions, nausea, and fatigue. The highlighted challenges included the need for larger sample sizes, long-term follow-up, optimal dosages, and studying diverse populations. Scientific Novelty: Explore the innovative realm of immunological drugs, a promising frontier in combating wound infections among military personnel during active hostilities. Conclusion: The review also identified new developments in immunomodulatory agents for military wound infection, which are effective in decreasing infection rates and enhancing the rate of wound healing.

show abstract

Section: Discussionmentioning

confidence: 99%

The use of immunological drugs for the treatment of wound infections in military personnel during hostilities

2024

Педагогічна Академія: Наукові Записки

View full text Add to dashboard Cite

show abstract

Neutralizing human monoclonal antibodies that target the PcrV component of the Type III Secretion System ofPseudomonas aeruginosaact through distinct mechanisms

Desveaux,

Faudry,

Contreras-Martel

et al. 2024

Preprint

View full text Add to dashboard Cite

Pseudomonas aeruginosa is a major human opportunistic pathogen associated with a high incidence of multi-drug resistance. The antibody-based blockade of P. aeruginosa virulence factors represents a promising alternative strategy to mitigate its infectivity. In this study, we employed single B cell sorting to isolate, from cystic fibrosis patients, human monoclonal antibodies (mAbs) targeting proteins from the P. aeruginosa Type 3 Secretion System (T3SS) and characterized a panel of mAbs directed at PscF and PcrV. Among those, two mAbs, P5B3 and P3D6, that bind to the injectisome tip protein PcrV, exhibited T3SS blocking activity. We solved the crystal structure of the P3D6 Fab-PcrV complex, which revealed that the Ab binds to the C-terminal region of PcrV. Further, we compared the T3SS-blocking activity of three PcrV-targeting mAbs, including two from previous independent studies, using two distinct assays to evaluate pore formation and toxin injection. We conducted a mechanistic and structural analysis of their modes of action through modeling based on the known structure of a functional homolog, SipD from Salmonella typhimurium. The analysis suggests that anti-PcrV mAbs may act through different mechanisms, ranging from preventing PcrV oligomerization to disrupting PcrV's scaffolding function, thereby inhibiting the assembly and function of the translocon pore. Our findings provide additional evidence that T3SS-targeting Abs, some capable of inhibiting virulence, are elicited in P. aeruginosa-infected patients. The results offer deeper insights into PcrV recognition by mAbs and their associated mechanisms of action, helping to identify which Abs are more likely to be therapeutically useful based on their mode of action and potency. This paves the way for developing effective alternatives to traditional antibiotics in the fight against this resilient pathogen.

show abstract

mRNA-based platform for preventing and treating Staphylococcus aureus by targeted staphylococcal enterotoxin B

Luo,

Xu,

Zhang

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Staphylococcus aureus (S. aureus) possesses numerous virulence factors, with the increasing prevalence of drug-resistant strains heightening the threat posed by this pathogen. Staphylococcal enterotoxin B (SEB), a highly conserved toxin secreted by S. aureus, is also recognized as a potential bioweapon with super-antigenic activity. SEB represents a promising target in efforts to combat infections caused by S. aureus. We developed mRNA-based vaccine and antibody targeting SEB for both prophylactic and therapeutic purposes in varying S. aureus infection conditions. The mSEB mRNA vaccine (10 μg per mouse) induces more robust and persistent immune responses, including higher antibody titers and specific cellular immune responses, compared to immunization with 30 μg of mSEB protein adjuvanted with aluminum phosphate. Additionally, the anti-SEB mRNA antibody maintains secretion of anti-SEB monoclonal antibody (mAb) with a dosage that is 10 times lower than purified protein administration. The mRNA-based antibody exhibits superior pharmacokinetic profiles compared to its protein counterparts, efficiently neutralizing SEB and clearing S. aureus from circulation. Both the mRNA vaccine and mRNA antibody demonstrate preventive and therapeutic effects by eliciting specific immune responses and generating high-affinity antibodies in mice. We have laid the groundwork for the development and evaluation of mRNA-based vaccines and antibodies targeting SEB produced by S. aureus. Our studies demonstrate that these approaches are more effective than traditional protein-based vaccines and antibodies in terms of inducing immune responses, pharmacokinetics, and their prophylactic or therapeutic efficacy against S. aureus infections.

show abstract

Vaccines and Monoclonal Antibodies as Alternative Strategies to Antibiotics to Fight Antimicrobial Resistance

Cited by 6 publications

References 159 publications

The use of immunological drugs for the treatment of wound infections in military personnel during hostilities

The use of immunological drugs for the treatment of wound infections in military personnel during hostilities

Neutralizing human monoclonal antibodies that target the PcrV component of the Type III Secretion System ofPseudomonas aeruginosaact through distinct mechanisms

mRNA-based platform for preventing and treating Staphylococcus aureus by targeted staphylococcal enterotoxin B

Contact Info

Product

Resources

About