On Monday morning at the Microbicides 2002 meeting in Antwerp, Dr Peggy Johnston of the US National Institute for Allergy and Infectious Diseases (NIAID), a co-sponsor of the meeting, reviewed similarities and differences between microbicides and mucosal vaccines. She defined the latter as vaccines that are directed at preventing mucosal transmission of HIV, regardless of how they are given to people. She stressed that both are needed and identified a number of common issues, which will be especially relevant when it comes to securing regulatory approval for partially-effective products that may be of greater use in some parts of the world than in others.
On Tuesday morning Dr Rupert Kaul – now at the University of Toronto, but previously at Oxford University and working in Nairobi, Kenya – reviewed what is known about mucosal immunity and its possible relevance to microbicide development.
Most HIV transmission happens across mucosal surfaces, and the properties of those surfaces account for why some kinds of sex, in particular, are riskier than others. In particular, the different structures and populations of cells of the immune system in the vagina, cervix and rectum account for why receptive anal sex is so much riskier than vaginal sex, which is riskier than insertive sex, whether heterosexual or homosexual, and oral sex.
Looking at how HIV is shed and acquired, viral load in semen was generally lower than in blood, but there were exceptions. Factors such as sexually transmitted infections increased viral load in semen, and antiretroviral treatment could reduce it.
In HIV positive women, HIV was detectable in vaginal fluids at least two thirds of the time, and could be elevated by sexually transmitted infections.
Gonorrhoea infection, although limited to mucosal areas, could increase the blood levels of HIV. A variety of possible reasons had been identified; it seemed that one of them is that the ability of CD8 cells (‘killer T-cells’) to control HIV is temporarily inhibited by gonorrhoea.
A key question is whether mucosal CD8 cells play any role in control of HIV shedding by positive people. If they do, then in theory a microbicide which interfered with this could have the effect of increasing HIV exposure rather than reducing it.
Antibodies against HIV have not yet been induced by vaccines, to the level where they could be protective against the virus. However, it has been possible to protect monkeys from mucosal exposure by injecting high levels of monoclonal antibodies into their bloodstream. The emergence of low-cost methods of mass-producing such antibodies could open the way to microbicides based on antibodies. If these reduced the dose of HIV to which people were exposed, this might be enough to enable people to mount protective immune responses to HIV rather than immune responses which enabled HIV to invade their bodies more efficiently.
In conclusion, he thought it would be very important to look for immune responses to HIV, and changes in other immune responses that could boost or inhibit the risk of infection, in people who were using microbicides. This would become even more important, as and when the use of microbicides can be combined with the use of vaccines.