HERPES

What are herpes infections?

There are eight known human herpes viruses, classified into three groups. Cold sores, which affect the majority of us, are caused by Herpes simplex (HSV) Type 1 (Figure 1); and genital herpes, one of the most common sexually transmitted diseases, is usually the result of infection by HSV-2 (although some cases are due to HSV 1), and chicken pox and shingles are manifestations of Varicella zoster infection. Following primary infection, the herpes viruses persist in one or more body cells (nerve cells in the case of HSV-1, -2 and -3) in a dormant form and may be reactivated, either spontaneously or when the immune system is depressed, possibly with more severe consequences than during the primary infection (e.g. shingles). Herpes viruses of the gamma type have been implicated in the development of various cancers, such as Kaposi's sarcoma.

Who does herpes affect?

Most children are exposed to HSV-1 and those who have a cold sore often become carriers and have recurrences. Cold sores are usually trivial, but in people undergoing immunosuppressive therapy, or who have cancer or AIDS, they can be life-threatening. Similarly, in a new-born baby, infection arising from a vaginal sore can be very serious. Until vaccines against Varicella became available, chickenpox was a common childhood infection and shingles, frequent in older people, is often accompanied by severe, long-lasting pain.

Present treatments and shortcomings

When it is latent, herpes virus is concealed inside cells, where it is invisible to the immune system. In cold sores, the cells concerned are nerves in the neck, while in genital herpes the virus lodges in the nerves in the lower spine. Varicella zoster, which causes chickenpox, hides in clusters of nerves alongside the spine.

Medical treatment deals with the symptoms, but does not eradicate the concealed virus infection. Milder outbreaks of oral or genital herpes are often treated with non-prescription topical preparations, but more serious or frequently recurring cases require other forms of medication.

Anti-herpes preparations which are available include aciclovir (Zovirax) and valaciclovir (Valtrex) from GlaxoSmithKline, famciclovir (Famvir) from Novartis, inosine probanex (Immunovir, Ardern), and the topical preparations idoxuridine (Herpid, Astellas) and penciclovir (Vectavir, Novartis). Most of these work by blocking replication of the viral DNA, preventing the formation of infectious particles. Ganciclovir (Cymvene, Roche), foscarnet (Foscavir, AstraZeneca) and cidofovir (Vistide, Pfizer), are used for the treatment of cytomegalovirus infections in AIDS and immunocompromised patients. The drawbacks of all of these anti-herpes preparations are the regularity with which they have to be applied, and the fact that they do not eliminate the latent virus from the body.

Table 1: The human herpes virus and the diseases they cause

What's in the development pipeline?

Development projects for herpes virus infections are mainly aimed at Herpes Simplex, Varicella Zoster and Cytomegalovirus. GlaxoSmithKline has its vaccine, Simplirix, in Phase 3 trial for the prevention of genital herpes and PowderMed has a vaccine in Phase 1 study for treating HSV-2 infections. This vaccine produces a response which may enable the virus to be eliminated, or help prevent the viral reactivation that leads to the recurrence of symptoms. Antigenics also has a therapeutic vaccine in Phase 1 trial that is intended to activate both helper and killer T-cells.

Live, attenuated (weakened) vaccines to protect against primary infection with the Varicella zoster virus (VCV), and so prevent chickenpox, are already available (Varivax, Sanofi Pasteur MSD; Varilrix, GSK), but Merck Sharp & Dohme's Zostavax has recently been made available for the prevention of virus reactivation in those over 60 who are already carriers and thus at risk of shingles. GSK has a VCV vaccine in development for primary prevention, which has now reached Phase 2 trial. Meanwhile, Janus Pharmaceuticals has a cream containing the antiviral sorivudine in Phase 1 study for the treatment of shingles eruptions and GlaxoSmithKline and XenoPort are developing XP13512 for treatment of the painful post-herpetic neuralgia (nerve pain) that often follows shingles. It is in Phase 2 study.

Cytomegalovirus (CMV) infections are mainly a problem in those with an impaired immune system. Vical is researching a DNA-based vaccine against CMV for the prevention of infections after blood cell transplants and this has reached Phase 2. Sanofiaventis also has a CMV vaccine in Phase 2 study for prevention of maternal-foetal transmission. Lastly, Viropharma is developing maribavir, a new type of antiviral for the prevention of reactivation of CMV following bone marrow transplantation. It too has reached Phase 2 trial.