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Biologics in Healthcare: Debridement, Antibodies, Vaccines and Adjuvants

• Debridement is the process of removing foreign material and dead tissue from wounds to facilitate healing.
• Proteolytic enzymes are used to aid in debridement, and can be applied topically in creams, ointments, or sprays.
• Common microbial enzymes used for debridement include collagenase, trypsin, and papain.
• Maggot saliva containing proteases can also be used to clean wounds.
• Antibodies, vaccines, and adjuvants are collectively known as biologics and have had a significant impact on healthcare management.
• Polyclonal antibody preparations have been used for passive immunization against infectious diseases and toxins for several decades.
• Antisera are antibody preparations obtained from animal sources, while immunoglobulin preparations are obtained from humans.
• Polyclonal antibody preparations can induce unwanted side effects, including hypersensitivity reactions.
• Monoclonal antibodies (mAbs) were first developed in the 1970s and are now widely used in diagnostic imaging and therapeutically for cancer, transplantation, and cardiovascular disease.
• mAbs can be conjugated to a radioisotope, drug, or toxin to deliver targeted treatment to specific cells in the body.
• Over 70 antibody-based products have gained FDA approval, including Remicade and Herceptin.
• Remicade is a chimeric mAb used to treat Crohn's disease, while Herceptin is a humanized antibody used for metastatic breast cancer.

Chimeric and Humanized Antibodies

• Simulect is a chimeric monoclonal antibody used for prophylaxis against acute organ rejection in allogeneic renal transplantation.
• Over half of all monoclonal antibodies are used for cancer detection/treatment.
• Murine monoclonal antibodies have limited therapeutic efficacy due to immunogenicity and HAMA response.
• Human antibody-producing lymphocytes can be rendered immortal by transformation or fusion with murine monoclonals or human lymphoblastoid cell lines, but these approaches are inefficient.
• Chimeric antibodies consist of mouse variable regions and human constant regions and are less immunogenic and display a prolonged serum half-life compared to murine antibodies.
• Clinical trials with chimeric antibodies have shown them to be generally safe and non-toxic, but repeated administration eventually raises the immune response in most recipients.
• Chimerization increases serum half-life by 5-fold and allows activation of Fc-mediated functions.
• Humanized antibodies transfer the nucleotide sequences coding for the CDR regions of the murine antibody into a human antibody gene, resulting in a hybrid antibody that is entirely human in nature except for the CDRs.
• Several humanized antibodies have gained market acceptance, such as Avastin, a recombinant humanized monoclonal IgG1 antibody used for first-line treatment of metastatic colorectal cancer.
• Avastin acts by inhibiting angiogenesis by binding to human vascular endothelial growth factor, preventing it from binding to its cell surface receptor.
• Antibody fragments such as F(ab), F(ab)2, and Fv are generated by recombinant DNA technology and are effective as therapeutics, but display greatly reduced half-lives and cannot initiate effector functions.
• Radiolabeled fragments may be better suited for diagnostic imaging purposes.

Overview of Traditional and Modern Vaccine Preparations

• Traditional vaccine preparations can be categorized into 6 groups, including live attenuated bacteria, dead or inactivated bacteria, inactivated virus, live attenuated viruses, toxoids, and pathogen-derived antigens.
• Recombinant DNA technology has enabled large-scale production of polypeptides from any pathogen, which can be used as subunit vaccines.
• Advantages of genetic engineering in vaccine production include clinically safe products produced by non-pathogenic hosts, unlimited supply, and consistent production of a defined product with fewer side effects.
• The first FDA-approved recombinant subunit vaccine was recombinant hepatitis B surface antigen (rHBsAg) in 1986, providing a clinically safe and unlimited supply of the vaccine.
• Prior to rHBsAg approval, hepatitis B vaccines were produced from infected human plasma, which had two major disadvantages: restricted vaccine supply and potential contamination with intact viable hepatitis B viral particles.
• In 1998, GSK secured FDA approval for Engerix B, a subunit vaccine containing purified rHBsAg, which is indicated for active immunization against all known serotypes of hepatitis B virus.
• Recombinant vaccines represent the largest group of biopharmaceuticals approved for animal use, with Porcilis PESTI and Bayovac CSF E2 targeting pigs.
• Peptide vaccines can be directly chemically synthesized and have been shown to confer immunological protection against viral and bacterial toxins.
• RNA vaccines elicit both humoral and cellular immune responses and were first approved for use against COVID-19 in December 2020.
• Advantages of RNA vaccines include easy design based on genetic sequencing, quick updates for emerging variants, inexpensive cell-free manufacture, non-infectious mRNA fragments, and flexibility to encode multiple viral proteins in a single vaccine.
• Two main categories of mRNA vaccines are conventional and self-amplifying mRNA (saRNA), with saRNA vaccines exhibiting enhanced antigen expression at lower doses compared to conventional mRNA.
• In vivo RNA vaccine delivery methods include lipid nanoparticles, electroporation, and needle-free jet injection.