Live attenuated HSV-2 vaccine: One step closer to reality

Hey, remember back in 2008, when I wrote a post on a neat idea in herpes vaccine design?

That paper was all ideas. Well, they just published a paper where they test some of the science of those ideas:

Herpes Simplex Virus 2 ICP0â Mutant Viruses Are Avirulent and Immunogenic: Implications for a Genital Herpes Vaccine

When most people think of 'herpes', they think of a 'social' disease. Yeah, the sores (wherever they crop up) are embarrassing, and its embarrassing telling your boyfriend/girlfriend about it, but its not like herpes kills anyone... right?

Well, no. Though its rare, babies born to HSV(+) mothers can get herpes encephalitis. Adults can get it too. Herpes is the leading cause of blindness in the US. And as Ive written about before, there is a connection between herpes and Alzheimers. Herpes isnt just a 'social' disease.

Scientists have been trying to make a HSV vaccine for years and years and years... its kinda like HIV-1 vaccine design. Everything they have tried has failed.

But HSV researchers have an option HIV researchers dont have: live attenuated vaccines.

(Previous post for more background)

Halford at al took a clever approach to 'deleting' the gene of interest, IPC0. When you are making a live attenuated virus for a vaccine, its not just a matter of 'Eh, we deleted the gene, lets go!'-- they 'deleted' IPC0 several ways, trying to minimize virulence, and maximize immunogenecity. In other words, they want to make a virus that is safe, but still have it annoy your immune system enough that you are protected from a real challenge.

One variant, HSV-2 0ÎNLS, where just a specific tiny region of the IPC0 gene was deleted, replicated just fine in cell lines but still had the phenotype they wanted (susceptibility to interferon).

What does this mean?

Well, if you take regular ol HSV-2 and put it in the eyes of mice, they die. In about a week. :-/

But if you take this attenuated strain, HSV-2 0ÎNLS, and put it in the eyes of mice... Theyre fine and dandy. And they were fine and dandy till the end of this portion of the experiment (60 days).

And I guess technically, they were better than fine and dandy. Because when mice vaccinated with the attenuated HSV-2 0ÎNLS were challenged with lethal doses of wild-type HSV-2 70-80 days post vaccination... they all survived.

100% dead, to 100% alive with vaccination.

Furthermore, one of the problems with HSV is that it moves. It travels up your neurons, and causes all kinds of trouble along the way. Well, the HSV-2 0ÎNLS used in these vaccines also had a fluorescent reporter built in. Cells infected with the attenuated virus glow green. So they could watch, to see what cells got infected with the vaccine virus, and where that virus went. Look at the poor little moosey mice (last figure) that got a wild-type+GFP virus. The infection starts at their eyes, and travels down their little faces, and their little eyes get all swollen :(

But the vaccine strain mice? Little glow in the eyes (where they were inoculated). Thats it.

There are many, many, many more questions to ask and answer before this would ever be available to humans. But I think this is a super neato step in a right direction!

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HSV goes latent. So someone will have to consider what long-term problems that may cause if the vaccine virus can go latent (maybe cancer).
I'm sure the vaccine would also be treated the way the HPV vaccine has been treated, or maybe even worse. No one thinks that their innocent child will be involved in activities or with people that could give them HSV, and some will claim that the vaccine will just encourage promiscuity.

This is a great result, and thanks for telling us. Is it a balancing act of making the immune system decide its worth reacting to the vaccine versus the vaccine being actually dangerous?

I think the picture you want is number 8, which has g008 at the end of the url it's here I hate scripted pages that make bookmarks, open in new tab, etc. malfunction.

Joe, the vaccine virus is shown not to spread beyong the innoculation site. That's what picture number 8 is showing. Normal HSV infections travel, and go dormant in places the virus has travelled to. If the vaccine does not replicate beyond the innoculation site then there is no dormant infection hidded up nerve fibres etc to re-activate.

Activities that can spread Oral herpes include having an infected parent (well done my mother, not giving it to any of her kids despite a recurrent infection on the lips), kissing (probably how my mother got it), having a cup of coffee from a cup in a shared kitchen or the kitchen of a friend with an infection (lower likelyhood, but still a risk).

A hypothetical complication that I don't think popped up (disclaimer: I only skimmed the paper) is the possibility that with high rates of vaccination, the virulence of HSV might increase to compensate. I bring this up because the principle of vaccination with a non-pathogenic type of herpesvirus is has been widely used in chickens to ward off Marek's disease, and there's been a recent trend where MDV has been becoming more virulent to increase its transmission.

Wait, do you refer to mice as "moose" too?

Interesting report Erv. The different live-virus approaches to HSV-2 vaccination being developed by William Halford and David Knipe look quite promising.

I'm still a little concened that these viruses persist at very low levels for some time, but as Halford et al. point out the experience with the VSV vaccine that works in a similar way is reassuring. Any risks associated with the possibility that the vaccine might mutate or recombine to produce a virulant virus are likely to be a lot lower than those associated with what is a very common infection. Still, perhaps longer term (2+ years?) animal studies should be undertaken to assess this risk before the vaccine is taken to clinical trials.

I have seen a perfectly healthy full term newborn die within a week because of herpes infection picked up at birth because mom's outbreak was undiagnosed. Let's hope this research pans out.

Wait, do you refer to mice as "moose" too?

Since the plural of both 'mice' and 'moose' is 'meese', there's obviously great potential for linguistic drift.

Meanwhile, how about encouraging young people to be very particular about who they slip with. It is best to only sleep with your wife or husband, who has only slept with you.

By William Wallace (not verified) on 19 Aug 2010 #permalink

Ahh. Freude a in sleep off their tongue, Wallarse? Ease orff.