POINTS OF VIEW APRIL 2015
Title - Vaccines in our Genes
By - Ray Spier, ISV Fellow
It has taken 35 years to arrive at a point which I envisaged when I was working on the production of Foot-and-Mouth Disease (FMD) vaccines at the, then, Animal Virus Research Institute at Pirbright, U.K.. Just following the publication of the papers showing that genetic engineering was practicable, it becomes obvious that to genetically engineer a cow to systemically produce its own vaccine to FMD was on the cards. The open option was to produce 7 vaccines (one for each type of virus) from 7 antibody genes that had been introduced into the genome. Later this approach would be better defined by discovering a single gene that would produce a cross-protective (broadly neutralising) antibody that would neutralise all 7 virus types.
A publication in this area in 1996 (1) evidenced the practicability of immunoprophylaxis by genetic immunisation. Since then the method (CRISPR-Cas9) for inserting foreign genes into specific loci in the genome have been developed (2) and numerous targets for this technique have been assayed in animal models (mice and monkeys) with many successful immunisations. At the time of this writing the targeted human diseases are HIV, Malaria, Influenza, Ebola and Hepatitis where some safety testing in humans is under way. (Carl Zimmer: Redesigning the body to fend off disease. International New York Times, 10/03/15, page 1). Additionally the technique has been defined as “Immunoprophylaxis by Gene Transfer” (IGT). To fully develop the potential of this technique the genes to be transferred should code for antibody molecules that can cross-neutralise the neutralisation epitopes of all the disease causing organisms, their types and subtypes.
The problems with the application of this technique may not be in the area of successful immunizations but rather in the area of regulation and ethics. Various conventions have been promulgated that forbid the genetic transformation of the human genome. This has been relaxed in some cases (the single gene disease of Cystic Fibrosis) but the regulations do not allow a genetic transformation that might be incorporated into the germ cells and become part of the germ line of the individual. This regulation may also be relaxed for some hereditary diseases such a Huntington’s Chorea.
There are several other issues connected to IGT such as the effect of having a number of different antibody molecules secreted into the blood stream without any control mechanism preventing overproduction and self-reactions to the influx of the additional components of the phenotype. A second possible scenario is how might we respond to a mistake in a gene insert. If the new gene interacts with other elements in the genome with harmful consequences how would we deal with the person and then that person as a potential progenitor of other disadvantaged persons in the future?
IGT is a powerful tool. As with all tools they can be used to bring benefits and to cause harms. Our job is to examine what we can do with this new tool, proceeding carefully and cautiously - but proceeding nonetheless.
(1) Immunoprophylaxis of allergen−induced immunoglobulin E synthesis and airway hyperresponsiveness in vivo by genetic immunization; Ching-Hsiang Hsu¬, Kaw-Yan Chua¬, Mi-Hua Tao, Yih-Loong Lai, Heuy-Dong Wu, Shau-Ku Huang & Kue-Hsiung Hsieh; Nature Medicine 2, 540 - 544 (1996) doi:10.1038/nm0596-540
(2) The new frontier of genome engineering with CRISPR-Cas9; Jennifer A Doudna and Emanuelle Charpentier; Science 346 No6213 13pp 2014 DOI 10.1126/science 1258096