Standard vaccines to prevent infectious diseases consist of killed or weakened pathogens or proteins from those microorganisms. Vaccines that treat cancer also rely on proteins. In contrast, a new kind of vaccine, which is poised to make major inroads in medicine, consists of genes. Genomic vaccines promise to offer many advantages, including fast manufacture when a virus, such as Zika or Ebola, suddenly becomes more virulent or widespread. They have been decades in the making, but dozens have now entered clinical trials.
Most vaccines work by teaching the immune system to recognize a foe. They accomplish this trick by delivering a dead or weakened pathogen; the immune system recognizes that certain bits of protein, called antigens, on the surface of the pathogen are foreign and prepares to pounce the next time it encounters them. (Many modern vaccines deliver only the antigens, leaving out the pathogens.) To treat cancer, doctors may deliver other proteins that enhance immune responses. These proteins can include the immune systems own guided missilesantibodies.
Genomic vaccines take the form of DNA or RNA that encodes desired proteins. On injection, the genes enter cells, which then churn out the selected proteins. Compared with manufacturing proteins in cell cultures or eggs, producing the genetic material should be simpler and less expensive. Further, a single vaccine can include the coding sequences for multiple proteins, and it can be changed readily if a pathogen mutates or properties need to be added. Public health experts, for instance, revise the flu vaccine annually, but sometimes the vaccine they choose does not match the viral strains that circulate when flu season comes. In the future, investigators could sequence the genomes of the circulating strains and produce a better-matched vaccine in weeks. Genomics also enables a new twist on a vaccination approach known as passive immune transfer, in which antibodies are delivered instead of antigens. Scientists can now identify people who are resistant to a pathogen, isolate the antibodies that provide that protection and design a gene sequence that will induce a persons cells to produce those antibodies.
With such goals in mind, the U.S. government, academic labs and companies large and small are pursuing the technology. A range of clinical trials to test safety and immunogenicity are under way, including for avian influenza, Ebola, hepatitis C, HIV, and breast, lung, prostate, pancreatic and other cancers. And at least one trial is looking at efficacy: the National Institutes of Health has begun a multisite clinical trial to see if a DNA vaccine can protect against Zika.
Meanwhile researchers are working to improve the technologyfor example, by finding more efficient ways to get the genes into cells and by improving the stability of the vaccines in heat. Oral delivery, which would be valuable where medical personnel are scarce, is not likely to be feasible anytime soon, but nasal administration is being studied as an alternative and is under study. Optimism is highthat any remaining obstacles can be solved.
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Genomic Vaccines – Scientific American
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