CRISPR hope for vax-resistant disease treatment


Gene-spliced antibodies show promise in mouse trials. Paul Biegler reports.


Gene-editing technology could find solutions where vaccine fail.

VICTOR HABBICK VISIONS/SCIENCE PHOTO LIBRARY

Scientists have used the gene-splicing technology CRISPR to make virus-busting antibodies for a range of diseases that cannot, to date, be prevented with vaccines.

The researchers, led by Justin Taylor of the Fred Hutchinson Cancer Research Centre in Seattle, US, say the technique could mean new ways to tackle infections including HIV, influenza and Epstein Barr Virus (EBV), which causes glandular fever.

The team used CRISPR to alter the genetic code of human B-cells, coaxing them to make antibodies against those viruses and another wily agent called Respiratory Syncytial Virus or RSV.

RSV is harmless in healthy people but can be deadly for the very young and old. It causes lung disease that, in the US, puts more than 50,000 kids under five in hospital and kills 14,000 adults over 65 every year.

To see if the rejigged B-cells would actually fight off RSV, Taylor’s team put CRISPR-modified mouse B-cells into healthy mice. The critters were then subjected to a largish dose of RSV up the nostrils. Five days later the researchers took lung samples to see if the virus had taken up residence. RSV was nearly undetectable.

It’s an approach that addresses two problems with the current mainstay in stopping infection before it starts: vaccination.

Vaccines challenge the body with a small dose of disease to spike immune cells into action. The cells can then be on war footing should the real illness come knocking down the track, helping them beat down the invader.

But vaccines for some illnesses have been devilishly difficult to make.

The first RSV vaccine trial in 1966 left many infants and toddlers with a severe form of the disease, ultimately killing two. A second trial in 2016 was ineffective.

HIV is another battlefront, with attempts to make a vaccine underway since the late 1980s.

“Our approach could be used to protect people against infections when a vaccine is not an option,” says Taylor.

“HIV is a great example of an infection in which a protective vaccine doesn’t exist.”

There is also a whole bunch of people for whom getting vaccinated is out of the question.

These include the sick, elderly and people getting cancer chemotherapy, whose immune system may be so weakened that a vax would simply overwhelm them. Vaccines are a particular threat for people whose immunity has been wiped out in preparation for a bone marrow transplant.

The team’s research therefore included a study that put engineered B-cells into mice that lacked immune cells altogether, mimicking extreme immunodeficiency. After 82 days the cells were still making enough antibody to protect the mice from RSV infection.

It’s a finding that could, ultimately, shift the odds for bone marrow transplant recipients.

“These people are susceptible to a wide variety of viral, bacterial and fungal infections that we could use this technique to protect against while their immune systems recover,” explains Taylor.

The research is published in the journal Science Immunology.

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Paul Biegler is a philosopher, physician and Adjunct Research Fellow in Bioethics at Monash University. He received the 2012 Australasian Association of Philosophy Media Prize and his book The Ethical Treatment of Depression (MIT Press 2011) won the Australian Museum Eureka Prize for Research in Ethics.
  1. https://www.cdc.gov/rsv/research/us-surveillance.html
  2. https://cvi.asm.org/content/23/3/189
  3. https://www.atsjournals.org/doi/pdf/10.1164/rccm.201901-0233ED
  4. https://www.who.int/immunization/research/development/hiv_vaccdev/en/
  5. http://immunology.sciencemag.org/lookup/doi/10.1126/sciimmunol.aax0644
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