Does gender matter for AIDS vaccines?

VaxGen's Phase III results brought attention to the question of whether a vaccine might work differently in different populations. Although inconclusive, the study's data raised questions about different levels of protection in various racial groups and in men and women. Discussions of potential differences between the sexes have led some scientists to re-examine a few previous studies which showed some evidence that vaccines might work differently in men and women.

The first indication of a possible gender gap in vaccine protection came in 2000 from two Phase III trials of a candidate vaccine against a strain of herpes virus (called HSV-2), which causes genital lesions. Among women who did not carry any other herpes viruses, the vaccine was 75% effective in preventing symptomatic disease. But among men, no protection was seen.

However, as with the VaxGen trial, the number of women in the HSV-2 studies was too small for firm conclusions to be drawn. So in November 2002 the vaccine's developer, GlaxoSmithKline, launched a second larger trial in 6,000 women, to find out whether the observation holds up.

If this trial confirms the initial trend, then the world could have its first sexspecific vaccine on its hands.

Historically, there's been no indication of gender or racial differences in how well vaccines work. Globally, millions of men, women, boys and girls of all races have been immunized against diseases, like measles, mumps, polio and tetanus. Yet there has been very little evidence of subgroup-specific effects for any of them.

So why are apparent differences emerging? Perhaps because the vaccines in question are targetting sexually-transmitted diseases (STDs). STDs start in the genital tract, which is the site of the most dramatic differences in men's and women's bodies, including distinct tissue types and immune defenses. These differences have long been linked to men's and women's varying symptoms from and susceptibility to STDs. Vaccines against STDs must protect in these varied environments. This is different from other viruses (for example, polio) that enter the body through the nasal and oral cavities, where men and women are very similar. There is no evidence that polio vaccine offers different types of protection to men and women.

Another example of a sex-specific vaccine for an STD comes from Merck & Co., which in November 2002 launched a large, women-only Phase III trial of a vaccine against human papillomavirus (HPV), a disease causeing genital warts and cervical cancer . The company has conducted its trials almost entirely in women because cervical cancer, the most serious outcome of HPV infection, occurs only in women. (Merck also plans a later test of its vaccine in men, in whom HPV causes warts and anal cancer.)

Will gender prove important for AIDS vaccines? Right now, no one knows. The only way to get an answer is through large-scale trials that enroll enough men and women for genderspecific effects to become apparent.

The content in this issue of VAX is based on articles by Mark Boaz, Patricia Kahn, and Emily Bass, originally appearing in the February-April and May-July 2003 issues of IAVI Report.