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Breaking away from traditional vaccines

Will the global demand for fast, effective vaccines transform the vaccine space?

Historically vaccines have been made from modified pathogenic agents employed to produce active immunity.  These include whole, inactivated pathogens such as the Salk poliovirus vaccine; immunity-producing fractions of the pathogen such as the hepatitis B vaccine; toxoids such as tetanus vaccine and attenuated infectious vaccines which remain infectious but do not produce clinical diseases, such as measles, mumps, and rubella vaccine.1  

Anti-Idiotypic Vaccines

A group of non-traditional vaccines is anti-idiotypic vaccines. In this case, an antibody that acts as a mimetic to the original antigen is injected into an animal which elicits an antibody response to the binding site of the mimetic antibody. When used as a vaccine, this approach elicits an antibody response that will also recognize the original antigen.  This non-traditional vaccine overcomes the obstacles of some conventional vaccines which include difficulty in culturing large quantities of some pathogens in vitro or poor humoral response to certain non-protein antigens such as polysaccharides or lipids.2  

Idiotype vaccines have the advantages of being non-infectious, can be raised against an antigen that is difficult to isolate, and may mimic challenging targets such as carbohydrates or lipids.3

Currently, one anti-idiotype vaccine, Racotumomab (Vaxira™), is approved for use in Argentina and Cuba for the treatment of solid tumors. Racotumumab triggers an immune response against the tumor antigen N-glycolyl GM3, a type of ganglioside present on the cell surface of malignant cells from lung and breast cancers and melanoma.4 In 2019 it was reported that anti-idiotype antibodies can specifically recognize and expand rare B cells that express a class of antibodies that are broadly neutralizing against HIV-1 in a mouse model.  An impendent to vaccine development against HIV-1 is that immunization with recombinant enveloped proteins elicit antibody responses that are type-specific but show little or no neutralization breadth against viral variants.5  Anti-idiotype antibody vaccines present a possibility to create vaccines that produce broadly neutralizing antibodies against HIV and other rapidly mutating viruses. 

The COVID19 pandemic led to the use of a novel vaccine design and perhaps this will result in more aggressive out-of-the-box approaches being considered for future vaccination efforts that may be needed when we are confronted with our next pandemic.

REFERENCES:
  1. National Research Council (US) Division of Health Promotion and Disease Prevention. Vaccine Supply and Innovation. Washington (DC): National Academies Press (US); 1985. 2, Vaccines: Past, Present, and Future. Available from: https://www.ncbi.nlm.nih.gov/books/NBK216821/
  2. Warren R.Q., Kennedy R.C. (1991) Anti-Idiotypic Antibodies as Potential Viral Vaccines. In: Cazenave PA. (eds) Anti-Idiotypic Vaccines. Progress in Vaccinology, vol 3. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-2992-6_7
  3. 1997 Elsevier Science B.V. All rights reserved. Idiotypes in Medicine: Autoimmunity, Infection and Cancer Y. Shoenfeld, R.C. Kennedy and S. Ferrone, editors.
  4. Alfonso M., Diaz, A., Hernandez AM, Perez A., Rodriguez, E. Bitton, R., et al. (March 2002) Journal of Immunology. 168 (5) 2523 – 9. .doi:10.4049/jimmunol.168.5.2523
  5. McGuire A., et al. Journal of Experimental Medicine, 216 (10), 2316-2330.
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