Potential for HSV-1 vaccination to reduce risk of HSV-1 encephalitis and/or Alzheimer's disease?

Abstract

Professor Itzhaki and her team report an interesting experiment in which vaccination of mice with mixed HSV-1 glycoproteins significantly reduced detectable latent HSV-1 in brain (from 41% to 7%) 5 months after subsequent challenge by ear scarification with a non-lethal dose of HSV-1 [18]. This work follows the earlier demonstration by other groups [6 – 8,11,21] that similar vaccines can prevent infection of, and establishment of latency in, the peripheral nervous system in mice. Peripheral infection with HSV-1 is extremely common in humans and may be associated with painful and tiresome, but not life-threatening, recurrent cold sores. Of much greater potential hazard is infection of the brain with HSV-1 since this occasionally causes severe, sometimes fatal, acute HSV-1 encephalitis. If Professor Itzhaki’s work is correct, it may also frequently establish latent CNS infection that increases the risk of developing Alzheimer’s disease (AD). Both these putative consequences of CNS infection with HSV-1 are serious and merit careful consideration of whether vaccination against HSV-1 can prevent them. Despite much consideration over many decades and quite a number of experimental studies in animals, the pathogenesis of acute HSV-1 encephalitis in humans remains a mystery [15]. It can arise at almost any age and without clear disposing factors. It is described in the immunocompromised but usually occurs in the apparently immunocompetent. It does not seem to represent a primary infection with the virus because it is common for those with the disease to possess serum antibodies at the start of the illness. There is usually no evidence of recent peripheral infection, in particular, cold sores. Its pathology offers some tantalizing clues in that the distribution of the acute necrotizing process is mainly confined to the temporal lobes and areas of the limbic system and prefrontal orbital cortex connected anatomically to medial temporal lobes and amygdala. Temporal lobes are often asymmetrically affected [9]. The virus is known from experimental studies to travel along neural pathways and this pattern of damage would fit with the acute infection having arisen in one anterior temporal lobe or closely adjacent structure. This might result from reactivation of latent infection at such a site given Itzhaki’s and others [3] evidence that latent infection occurs in the brain in a sizable proportion of adults. In experimental animals reactivation of HSV-1 infection in brain can be triggered by immunosuppression or hormonal changes provoked by stress [16]. It is conceivable that such factors could operate to give rise to apparently spontaneous reactivation in humans.