On antiserum and Ebola virus

In 1925, dogsledders raced through the frozen Alaskan bush to bring antiserum to the isolated village of Nome.  The antiserum arrived in time, saved the lives of many villagers from the horrors of diphtheria, and inspired the Iditarod, a famous race in celebration of the dog sledders' heroic feat.

ResearchBlogging.orgWest Africa could use a similar effort today.  Richard Harris's blog at NPR has a good story about doctors' efforts to develop and use antiserum to treat Ebola.  According to ABC news, Dr. Kent Brantly, who is being seen at Emory University Hospital was treated with antiserum as was the other aid worker, Nancy Writebol.

Antiserum is the liquid portion of blood that contains the antibody proteins.  Antibodies are present in your blood all the time, but special cells, the B cells, produce more of them when your body is trying to fight off some kind of disease.  The problem is that it takes time for your body to make these proteins and even then, the proteins you make might not work very well.

When immediate protection is needed, antiserum can act much more quickly.  That's why we use antiserum to treat cases of snake bite, hepatitis exposure, and to protect people from tetanus. And that's why it was important for stopping diphtheria and saving the children in Nome.

I thought you might like to see a close up view of what these kinds of antibodies look like.

This image is from a structure I downloaded from the NCBI, 3CSY, and viewed in Molecule World.  It shows a portion of an antibody, called the Fab fragment, bound to two of the glycoproteins from the outside of the Ebola virus.  The antibodies were derived from someone who was infected with Ebola in the 1995 Kikwit outbreak and survived (1).

Ebola_glycoproteins_abs

 

Zooming in lets me see how tightly the antibody and the viral proteins fit together.

antibody zoom

We can see where the antibody binds to the viral protein, right near some of the sugar residues. Knowing the amino acid sequence at the antibody binding site can help scientists engineer protective antibodies and produce them in E. coli or other other organisms.  These kinds of treatments aren't perfect, but they can help Ebola victims.

I made all the pictures from images saved in Molecule World.

Reference:
Lee JE, Fusco ML, Hessell AJ, Oswald WB, Burton DR, & Saphire EO (2008). Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor. Nature, 454 (7201), 177-82 PMID: 18615077

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So If the serum is effective why aren't they using it more?

By jada sarfate (not verified) on 03 Aug 2014 #permalink

Great question! Maybe if there were larger amounts available they would.

Isn't there also a non-zero danger of transmitting other diseases through serum? I mean, it's a heck of a thing to save someone from Ebola only to give them HIV, or syphilis, or HepC. So you have to screen donors that are known to have survived Ebola *and* are free of serious bloodborne pathogens. And that might be a pretty small pool of people, and then you have to find the willing ones.

Also, are there risks of immune response to other material in the serum, or is it clean enough you don't have to worry about blood type and MHC matching?

By JustaTech (not verified) on 12 Aug 2014 #permalink

@JustaTech: you're absolutely right. Other diseases like HIV and hepatitis B can certainly be transmitted through serum.

A better way to deliver passive immunity is probably to purify the antibodies from the serum. We can also make antibodies in other animals, like horses, and use those antibodies to provide passive immunity. This is done in the case of snake bite anti-toxin and I think tetanus anti-toxin, too.

Providing passive immunity through antibodies isn't a perfect treatment. As you noted, people can develop an immune response to antibodies and this can have severe consequences. However, the technology for engineering antibodies has improved greatly over the past years and I think people have been able to change the sequences and make them less likely to trigger an immune response.

Interestingly, I learned just recently about a biotech company that's manufacturing antibodies in tobacco plants. This seems pretty promising. Now, the challenge is to figure out how best to resolve the questions of safety and access.

It's not easy to choose between the prospects of conducting experiments on desperate people or letting the disease follow it's natural course.

Viruses are usually intracellular and antibodies are ineffective. A cell mediated response is necessary to kill the infected cell. They might bind circulating virus and reduce total load, but won't be able to kill intracellular virus.

By Brian Slade (not verified) on 19 Aug 2014 #permalink

Cellular immunity is an important mechanism for defense, but antibodies can be important, too.

In the image that I posted above, the antibodies are binding to a protein that would be found on the outside of a viral particle. These kinds of antibodies can help in the immune response by blocking viruses from entering a cell.

Here's a great article on this and it's open access:

Antibody-mediated Neutralization of Ebola Virus Can Occur by Two Distinct Mechanisms
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351102/