vaccination against zoster

Ian A. York york at mbcrr.dfci.harvard.edu
Tue Apr 11 10:27:16 EST 1995


In article <30DE9342E2D at prl.pulmonary.ubc.ca> DANDERSON at PRL.PULMONARY.UBC.CA writes:
>
>An immunization attempt would be interesting but I have 
>a mechanistic question.  Do these patients with zoster have a 
>depressed cellular response in the face of a sufficient humoral 
>response.  Is the mechanism of this selective immunosuppression 
>known?? 

	As far as I know, the situation in zoster is not well understood 
(as is the case with most viral pathogenesis questions, of course).  The 
related virus, herpes simplex virus, has been studied in more detail (and 
I know more about it, note the cunning switch of fields).  With HSV 
reactivation, the virus seems to reactivate in spite of a perfectly 
competent humoral immune response.  There is often a *moderate* 
suppression of the cellular immune response, concurrent with the 
reactivation.  The most probable explanation is that HSV takes advantage 
of this suppression to show overt symptoms, but it is almost equally 
possible that some of this immune suppression is actually mediated by the 
virus itself.  (The timing is not much help.  Immune suppression is seen 
before the clinical onset of cold sores, but a clinically apparent cold 
sore represents probably millions of infected cells, so this may not tell 
much about what's happening when the infection actually begins. 
Furthermore, the cold sore may even represent the host response to the 
virus, since there is an immune infiltrate at that time.)  

I don't find the degree of immune suppression in HSV enough to really 
account for reactivation; for one thing, the many other latent/persistent 
viruses in everyone don't reactivate at the same time.  Certainly, 
someone who has recurrent cold sores is not at greater risk of, say, 
Pneumocytis carnii pneumonia or the other hallmarks of immune 
deficiency.  HSV does have a pretty potent spectrum of immune evasion 
mechanisms; zoster probably does as well (because every herpes virus 
that's been examined in detail does), although not all the ones in HSV 
are reflected in VZV.  

On the third, or fourth, hand, people who have suppressed cellular 
immunity do have problems with recurrent herpes infections, including 
HSV, cytomegalovirus (in AIDS patients, for example), EBV (transplant 
patients eg) and VZV.  So, to summarize the above, it seems very likely 
that humoral immunity is not enough to keep a herpes virus under 
control.  This is not very surprising, of course, because these are the 
paradigms of intracellular viruses, so antibody has little chance to 
impact on them.  (This says nothing about the ability of antibody to 
*prevent and initial infection*, as in vaccines; there you're starting 
with extracellular virus.)   "Selective immunosuppression of cellular 
immune response" is probably not strictly correct - I prefer phrases like 
"immune evasion" - but to an approximation it reflects the situation.  
	
References and reviews for the above statements available on request.

Ian
-- 
Ian York   (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-3921     Fax  (617)-632-2627




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