Question: Herpes II Treatment -- Vaccination?

Ian A. York york at mbcrr.dfci.harvard.edu
Tue Aug 8 08:55:44 EST 1995


In article <406qbv$ft4 at saba.info.ucla.edu> jonathan at IME.UCLA.EDU (Jonathan E. Katz) writes:
>
>  Wouldnt an effective vaccination vs. HSV II also be, essentially, a
>cure?  As far as I understand, HSV comes out of latency perioically and
>is "forced" back into hiding by an increased response from the immune
>system.  If an infected person were to be vaccinated, it would keep
>that person's immune system at a higher state vs. the virus, possibly
>reducing shedding and outbreaks.  

Maybe.  However, the major flaw in this argument is that HSV normally 
reactivates in spite of a pretty potent immune response.  The trigger for 
reactivation is not really clear, and one hypothesis is that immune 
suppression is one.  Clearly profound immune suppression is one, but it 
isn't clear at all that HSV normally requires mild or moderate immune 
suppression to reactivate.  

A number of groups have found a mild or moderate immune suppression 
during reactivation.  I'm not completely convinced that this is a cause 
of the reactivation; it might be an effect, since HSV (as with many other 
viruses) can probably cause mild immune suppression itself.  The finding 
that immune suppression precedes detectable infection is not definitivce 
either, since detectable infection presumably means that there are 
several million cells infected already.  

Finally, it depends on the vaccine.  If it's a pure antibody generator, 
it very likely will have little effect on reactivation.  Normally HSV can 
reactivate in spite of high and constant antibody titers.  Cellular 
immunity is likely more important for clearing (and perhaps preventing) 
recurrent infection; so this would likely require a live (modified live) 
vaccine.  

Note that HSV has many methods of evading the immune system, both humoral 
and cellular.  Antibody will (probably) prevent the initial infection, 
but the clearance of existing virus, or prevention of recurrent 
infection, is *much* more complicated.  

Having said that, there is still a reasonable chance that vaccines will 
at the least reduce the frequency of recurrent infection, and that is 
indeed one of the aims of the vaccine.  
>
>  Additional thoughts:  Over time, the virus would possibly be removed
>from the system as infected neurons go active and become destroyed
>without productivly affecting other neurons.  

There's a lot of debate in the field as to whether HSV infected neurons 
are actually killed, either by the immune system or by the direct 
infection.  For a view against, check out some of Anthony Simmons' papers 
(try on in J Exp Med around 1992 or so).  However, it is possible (but 
far from certain) that the virus might be cleared this way. 

It's a very complicated situation.

Ian


-- 
Ian York (york at mbcrr.harvard.edu) 
"As things are, most Usenet postings are of no interest to socially 
well-adjusted people over the age of twelve." -Nature 376:200 (1995)



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