Vaccines against herpes and HPV on their way

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Vaccines for two of the most common sexually transmitted infections are being developed, the 42nd Interscience Conference on Antimicrobial Agents and Chemeotherapy was told last week in San Diego.

The vaccines closest to availability are ones that protect against the virus that causes genital warts and cervical and anal cancer - the human papilloma virus (HPV).

There are over 100 kinds of HPV, but some subtypes are much more common. Types six and 11 cause 90 per cent of obvious genital warts, but do not cause cancer. Types 16 and 18 do not cause obvious warts, but cause 50% and 14% of cancers respectively.

Glossary

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

herpes simplex virus (HSV)

A viral infection which may cause sores around the mouth or genitals.

cervix

The cervix is the neck of the womb, a tight ‘collar’ of tissue that closes off the womb except during childbirth. Cancerous changes are most likely in the transformation zone where the vaginal epithelium (lining) and the lining of the womb meet.

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

immune response

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

The vaccines furthest along are ones for HPV types 16 and 11, both being developed by Merck. In a phase III trial, the type 16 vaccine was given to 129 HPV-uninfected female university students. During the three year trial, no woman given the vaccine caught HPV-16, whereas 14 women given either a placebo or the HPV-11 vaccine caught it - matching the infection rate among the general population. In another, larger trial, there were no HPV-16 infections among a group of 950 women, compared with 41 in a control group. International trials are underway.

The point of giving some subjects the HPV-11 vaccine was to see if a vaccine against one HPV type protected against another - clearly it didn't. Licensed vaccines will be devised to protect against several HPV types.

HPV vaccines are being studied for therapeutic use as well as preventive use, with the idea that if HPV infection can be eradicated in women (or men) with pre-cancerous lesions (low-grade CIN, including lesions that are too 'early' to be operated on, or which recur after operations to remove them), it may prevent the later development of cancers (cervical or anal). An immune response to an HPV vaccine may also be helpful in treating cancer induced by the virus.

At present, studies of preventive and therapeutic vaccines do not appear to be taking place in HIV-positive populations, despite the high prevalence of HPV and the increased incidence of HPV-related lesions compared with the rest of the population.

Promoting HPV vaccine uptake

HPV is the most common sexually transmitted infection of all. 28 per cent of women acquire HPV before they are 20, and 75 per cent of sexually active adults will eventually get it. Because HPV is so common in adulthood, HPV vaccines would have to be given to adolescents before they had sexual experience.

Researcher Dr Laura Koutsky of Washington State University commented that this may face social resistance, especially in the case of young men, for whom HPV infection is only really dangerous if they are also infected with HIV.

Cervical cancer is common in young women, but other HPV-related cancers only occur in later years - except in people with HIV. HIV positive gay men and women are 70 times more likely to develop anal cancer.

At present pap screening is used to detect the tissue changes caused by HPV that can lead to cervical and anal cancers. But with up to 50 per cent of female university students developing potentially pre-cancerous changes, but only 0.1 per cent going on to develop cancer, pap screening is an expensive method of prevention.

Dr Koutsky commented that vaccines are expensive too, that repeat innoculations might be needed - protection fades after three years - and that there might be social resistance to giving them to prepubescent teenagers. "It's going to be tricky telling a parent that their young daughter needs a genital warts vaccine!" She said.

But she added: "It will be easier if it's sold as an anti-cancer vaccine, or to prevent the need for future pap screening."

Herpes vaccine

The other common STI for which a vaccine is likely is herpes - specifically the genital herpes virus, HSV-2 (HSV-1, the cold sore virus, also causes genital herpes). HSV infection is about one-tenth as common as HPV in the general population, but approaches 50 per cent among gay men, and 60-80 per cent among people with HIV. Only 20 per cent of infected people get the characteristic repeated attacks of herpes sores - but completely asymptomatic people are also infectious at times. Herpes infection also increases the likelihood of both catching and transmitting HIV by 80 per cent.

In one trial, people with neither type of HSV, but whose partners had HSV-2, were given a GlaxoSmithKline HSV-2 vaccine.

The results were unexpected. The vaccine conveyed 32-40 per cent more protection against HSV-2 infection, and 75 per cent more protection against actually developing herpes symptoms (i.e. only a quarter of the rate of symptomatic herpes was observed, compared with the general population).

But it didn't protect people who already had HSV-1: and, more unexpectedly, it only worked for women. Men derived no protection from it at all - in fact a few more of the male vaccine recipients caught herpes than those not given it.

Why? Researcher Lawrence Stanberry commented that women get herpes infections through the mucous membranes lining the cervix and vagina, whereas men tend to get them through broken skin. So the vaccine may be 'armouring' the membrane cells, but is not at high enough concentrations to get into the rest of the body. However, even protecting HSV-1 negative women would be enough to bring down the genital herpes rate among the whole population.

He said that a herpes vaccine was at least five years away from being a clinical reality - but added that scientists had already been looking for one for 60 years.

Researchers are also trying to develop vaccines against gonorrhoea and chlamydia. But the ability of these bacteria to elude immune response, and in gonorroea's case the fact that only humans get it, so animals cannot be tested, means that jabs for these STIs are a much greater development challenge and are much further away.

References

Koutsky LA. Vaccines for the prevention of STDs: HPV vaccines (presentation, Vaccines for the prevention of STDs symposium). 42nd ICAAC, San Diego, 2002.

Stanberry LR. Vaccines for the prevention of STDs: HSV vaccines (presentation, Vaccines for the prevention of STDs symposium). 42nd ICAAC, San Diego, 2002.