Antibody-Based Immunotherapies as a Tool for Tackling Multidrug-Resistant Bacterial Infections

Abstract

The discovery of antimicrobials is an outstanding achievement of mankind that led to the development of modern medicine. However, increasing antimicrobial resistance observed worldwide is rendering commercially available antimicrobials ineffective. This problem results from the bacterial ability to adapt to selective pressure, leading to the development or acquisition of multiple types of resistance mechanisms that can severely affect the efficacy of antimicrobials. The misuse, over-prescription, and poor treatment adherence by patients are factors strongly aggravating this issue, with an epidemic of infections untreatable by first-line therapies occurring over decades. Alternatives are required to tackle this problem, and immunotherapies are emerging as pathogen-specific and nonresistance-generating alternatives to antimicrobials. In this work, four types of antibody formats and their potential for the development of antibody-based immunotherapies against bacteria are discussed. These antibody isotypes include conventional mammalian polyclonal antibodies that are used for the neutralization of toxins; conventional mammalian monoclonal antibodies that currently have 100 IgG mAbs approved for therapeutic use; immunoglobulin Y found in birds and an excellent source of high-quality polyclonal antibodies able to be purified noninvasively from egg yolks; and single domain antibodies (also known as nanobodies), a recently discovered antibody format (found in camelids and nurse sharks) that allows for a low-cost synthesis in microbial systems, access to hidden or hard-to-reach epitopes, and exhibits a high modularity for the development of complex structures.

A Polyclonal Antibody against a Burkholderia cenocepacia OmpA-like Protein Strongly Impairs Pseudomonas aeruginosa and B. multivorans Virulence

“…The exploitation of immunogenic surface-exposed proteins of pathogens to raise antibodies has the potential to generate novel therapeutics to surpass the growing inefficacy of antibiotics. Research on pathogen-specific antibodies is a fast-developing area, with large interest for infections caused by antimicrobial resistant bacteria [ 19 ]. Some studies using antibodies against P. aeruginosa have exhibited significant potential in preclinical infection models, although none are currently available [ 20 ].…”

“…However, the major drawback of these aggressive antibiotic therapies is a faster development of antimicrobial resistance and the lack of efficient therapies during exacerbation periods [ 17 ], highlighting the urgent need for new alternatives to fight these infections. Antibody-based immunotherapies allow a very specific activity without the risk of developing resistance in bacteria [ 19 ]. These strategies act by an assortment of mechanisms, including binding to antigens and preventing adherence and inhibiting other important steps of infection, or by mechanisms dependent on mediators, like antibody-mediated cellular cytotoxicity, complement-dependent cytotoxicity, or opsonization [ 19 ].…”

“…Antibody-based immunotherapies allow a very specific activity without the risk of developing resistance in bacteria [ 19 ]. These strategies act by an assortment of mechanisms, including binding to antigens and preventing adherence and inhibiting other important steps of infection, or by mechanisms dependent on mediators, like antibody-mediated cellular cytotoxicity, complement-dependent cytotoxicity, or opsonization [ 19 ]. Several studies are currently being performed with potential new targets for the development of these new strategies [ 20 ].…”

IgY Antibodies from Birds: A Review on Affinity and Avidity

“…IgY antibodies are molecules of great interest for immunotherapy, immunodiagnosis, and basic research [19][20][21][22][23][24]. The production of IgY antibodies fulfils the current need for reducing, replacing, and improving the use of animals, since IgY antibodies can be produced in laying hens instead of using mammals, leading to less exposure to suffering and a significant reduction in the number of animals used [25].…”

Effects of High-Biotin Sample Interference on Antibody Concentrations in Sandwich Immunoassays

“…Vaccines 2023, 11, 1627 2 of 12 IgY antibodies can be obtained in larger quantities from the egg yolks of immunized laying hens compared to those obtained from other traditional sources, such as serum from rats, rabbits, goats, and sheep [10]. Unlike traditional mammalian antibody production, which could involve blood collection that can be stressful, other invasive procedures, and even sacrificing the animal [11], this non-invasive egg collection and IgY extraction from egg yolk is cost-effective and ethical and is a sustainable source of antibodies [12]. Furthermore, egg yolk antibodies do not interact with rheumatoid factors in the serum of mammals and do not bind to proteins A and G, mammalian Fc receptors, or mammalian complements [13].…”