title: Benefits of using heterologous polyclonal antibodies and potential applications to new and undertreated infectious pathogens.
abstract: BACKGROUND
  Passive immunotherapy using polyclonal antibodies (immunoglobulins) has been used for over a century in the treatment and post-exposure prophylaxis of various infections and toxins. Heterologous polyclonal antibodies are obtained from animals hyperimmunised with a pathogen or toxin.
  
  
  OBJECTIVE
  The aims of this review are to examine the history of animal polyclonal antibody therapy use, their development into safe and effective products and the potential application to humans for emerging and neglected infectious diseases.
  
  
  METHODS
  A literature search of OVID Medline and OVID Embase databases was undertaken to identify articles on the safety, efficacy and ongoing development of polyclonal antibodies. The search contained database-specific MeSH and EMTREE terms in combination with pertinent text-words: polyclonal antibodies and rare/neglected diseases, antivenins, immunoglobulins, serum sickness, anaphylaxis, drug safety, post marketing surveillance, rabies, human influenza, Dengue, West Nile, Nipah, Hendra, Marburg, MERS, Hemorrhagic Fever Virus, and Crimean-Congo. No language limits were applied. The final search was completed on 20.06.2015. Of 1960 articles, title searches excluded many irrelevant articles, yielding 303 articles read in full. Of these, 179 are referenced in this study.
  
  
  RESULTS
  Serum therapy was first used in the 1890s against diphtheria. Early preparation techniques yielded products contaminated with reactogenic animal proteins. The introduction of enzymatic digestion, and purification techniques substantially improved their safety profile. The removal of the Fc fragment of antibodies further reduces hypersensitivity reactions. Clinical studies have demonstrated the efficacy of polyclonal antibodies against various infections, toxins and venoms. Products are being developed against infections for which prophylactic and therapeutic options are currently limited, such as avian influenza, Ebola and other zoonotic viruses.
  
  
  CONCLUSIONS
  Polyclonal antibodies have been successfully applied to rabies, envenomation and intoxication. Polyclonal production provides an exciting opportunity to revolutionise the prognosis of both longstanding neglected tropical diseases as well as emerging infectious threats to humans.
authors.affiliation: The Children's Hospital, Westmead, Sydney, Australia. Electronic address: rushmi7@gmail.com.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Dixit
authors.affiliation: Biointelect, Sydney, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: Herz
authors.affiliation: University of Southampton, Southampton, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Dalton
authors.affiliation: The Children's Hospital, Westmead, Sydney, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Booy
mesh_terms: D000707:Anaphylaxis / Q000517:prevention & control; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000627:therapeutic use*; D000992:Antitoxins / Q000627:therapeutic use; D000997:Antivenins / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003141:Communicable Diseases / Q000628:therapy*; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007116:Immunization, Passive / Q000266:history*; D056990:Post-Exposure Prophylaxis
chemical_list: D000906:Antibodies; D000992:Antitoxins; D000997:Antivenins
keywords: Antitoxin; Antivenin; Arboviruses; Immunotherapy; Influenza