david_knipe.jpgThe herpes virus must make for interesting small talk at parties...  What first got you interested in this area?
I got interested in viruses in college through genetics and cell biology courses.  And then I had mononucleosis and learned that it was caused by a herpes virus.  I got interested in the herpes viruses through that, but I didn't end up studying Epstein-Barr virus, the herpes virus that causes mono, but instead started working on HSV because it was easier to work with in cell culture in the laboratory.

 

What percentage of people carry HSV?
In the U.S., about 70% of the population has antibodies specific to HSV-1, which causes cold sores or fever blisters.  And about 20% of the U.S. population has antibodies spec for HSV-2, which causes genital herpes.  They may not have known that they had cold sores or genital herpes, but they've been exposed to the virus and potentially have the virus latent in their nerve cells.

 

I understand your lab has developed a vaccine against HSV-2.  Would a vaccine for HSV-2 help someone who is already infected?  Who is the target of the vaccine?
We plan to test the vaccine against both people who are uninfected and people that are already infected.  In animal models, the vaccine has worked to prevent infection in mice and guinea pigs and it has worked in guinea pigs to reduce recurrent infections if the vaccine is given after the animals are already infected.  We plan to test it both against people that are not infected yet and in people that are already infected.

 

Is there any progress to report in the vaccine trials?
The vaccine has been licensed by a company that was called Acambis, now it's part of Sanofi-Pasteur, and they are working on produce the vaccine for clinical trials.  Hopefully the trials will be soon.

 

Now, the vaccine strain is a replication-defective mutant.  You need a lot of viruses to make a vaccine.  How do you grow a big batch of viruses that don't replicate?
The virus is engineered to be defective for two essential viral genes, but it's grown in a special cell line that has the two viral genes introduced into them.  So it will grow in this special cell line that we call a "complimenting cell line", but when it goes into normal cells in the body or in culture, it will only go part way through the replication cycle.

 

HSV-2 is sexually transmitted, but so is the human papilloma virus (HPV), for which we have a vaccine.  The HPV vaccine has been controversial.  Proponents say it's safe and will save lives, but opponents say being vaccinated against HPV, which causes some kinds of cervical cancer, will give vaccinated girls and women the mistaken impression that they're protected from all sorts of sexually transmitted diseases.  Once your vaccine is approved for use, do you expect to see the kind of public fight we've seen over the HPV vaccine?
There may be some of that response, but hopefully the HPV vaccine has paved the way for future acceptance of sexually transmitted disease vaccines.  Genital herpes is an immediate disease, and there are symptoms that people want to alleviate, as opposed to HPV and cervical carcinoma, which is a more long-term concern.  In the studies that some of the social scientists have done, it appears that there is more of an immediate concern about genital herpes, and hopefully that will translate into a more immediate acceptance of the vaccine.

 

What do you think is the most understudied microbial system? 
I used to think it was malaria, but with the increased funding that the Gates Foundation and others have brought for malaria, it may not be any more.  Maybe now it's some of the new herpes viruses that are emerging.  One new herpes virus that we just heard about recently is that there's some evidence that there's a herpes virus of coral that might be a contributor to some of the destruction of the coral reefs.  Finding that herpes virus needs to be done.

 

What is your favorite microbe?
I guess I'll show my prejudice and say that HSV is very intriguing.  But I like viruses in general.

 

What advice would you give students about life as a microbiologist working in academia?
Stay focused on hypothesis-driven science.  If you decide to get into translational applications, clinical applications of the basic science, have that as a side project, because it's a long haul developing things like our vaccine.

 

What is something about you that most people don't know?
I suppose it would be that I grew up in rural Ohio, on a farm.  I'm the first person from my father's family to go to college.


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