Monoclonal Antibodies Against Infectious Microbes: So Long and Too Little!

Abstract

Monoclonal antibodies (mAbs) as alternatives or more often as complementary to the conventional antimicrobials are being developed for the management of infectious conditions for the past two decades. These pharmacotherapeutic strategies are inevitable as the burden of antimicrobial resistance is far-reaching in recent times. MAbs are part of the targeted pharmacotherapy armamentarium with high degree of specificity – hence, exert comparatively superior efficacy and tolerability than the conventional polyclonal antisera. So far, only five mAbs have been approved for the management of infectious states – since, the marketing authorization (1998) given to palivizumab (Synagis®) for the prophylaxis of lower respiratory tract disease caused by respiratory syncytial virus in pediatric patients. Ibalizumab-uiyk (Trogarzo™) used for the management of multidrug resistant HIV-1 infection not yielding to at least 10 antiretroviral drugs previously was approved recently. Among the three antibacterial mAbs, raxibacumab (ABthrax®/ Anthrin®) and obiltoxaximab (Anthim®) are indicated for the treatment and prophylaxis of inhalation anthrax due to Bacillus anthracis; bezlotoxumab (Zinplava®) is used to reduce the recurrence of Clostridium difficile infection. There are also around 30 and 15 mAbs in different phases of development for viral and bacterial conditions. As alternatives to the traditional antivirals and antibacterials, the antimicrobial mAbs are the need of the hour. These mAbs are more relevant in the management of conditions like emerging viral outbreaks wherein there is a lack of prophylactic vaccines. The current cutting-edge engineering technologies revolutionizing the production of mAbs include phage-displayed antibody libraries, cloning from single-memory B cells or single-antibody-secreting plasma B cells, proteomics-directed cloning of mAbs from serum clubbed with high-throughput sequencing techniques. Yet, the cost of manufacture continues to be the main limiting factor.

Monoclonal Antibodies as a Therapeutic Strategy against Multidrug-Resistant Bacterial Infections in a Post-COVID-19 Era

“…Furthermore, highly conserved outer membrane proteins, while suitable as targets, are often masked by bacterial cell surface carbohydrates, making them less accessible to mAbs. Second, the variability in exopolysaccharide structures across serotypes poses a challenge, as a single mAb may not effectively target all variations [75]. For example, Streptococcus pneumoniae, a common cause of pneumonia and meningitis, produces a capsule composed of exopolysaccharides.…”

Immune-based Therapies—What the Emergency Physician Needs to Know

“… 45 Raxibacumab and obiltoxaximab are mAbs approved for the treatment and prophylaxis of inhalational anthrax due to Bacillus anthracis spores, and bezlotoxumab is a mAb used to reduce the recurrence of Clostridium difficile infections. 46 Ranibizumab and aflibercept are 2 vascular endothelial growth factor inhibitors approved for the treatment of diabetic macular edema, among other ocular conditions. 47 Basiliximab is an IL-2 antagonist approved as immunosuppressive therapy after renal transplantation.…”

Development and Research Progress of Anti-Drug Resistant Bacteria Drugs

“…43 The new inhaled anthrax treatment, obiltoxaximab, is a monoclonal antibody against the protective antigen of Bacillus anthracis and is designed to neutralize the toxin produced by B. anthracis to prevent the bacterium from binding to the cellular receptor. 44 Obiltoxaximab alone or in combination with antibiotics remarkably improved the survival rate of rabbits who inhaled a challenge dose of B. anthracis spores without interfering with immune development. 45 The most frequently reported side effects of obiltoxaximab include headache, itching, upper respiratory tract infection, cough, stuffy nose, and hives, as well as bruising, swelling, and pain at the injection site.…”