Understanding Routes of Transmission

Why do vaccines need to be tested in different populations?

Instead of conducting one large trial to see if an AIDS vaccine is successful, most vaccine developers plan on multiple trials of vaccines. One important reason for this strategy is that there are several different ways that people can become infected with HIV. HIV is passed or 'transmitted' from one person to another through close contact with body fluids that contain the virus (blood, semen, vaginal secretions or breast milk). Only certain types of contact with these fluids can lead to infection. These include unprotected vaginal or anal sex (sex without a condom); breastfeeding; and the use of a needle that has been contaminated with HIV-infected blood, as can happen when illegal drugs, such as heroin, are injected into the blood. This is called 'intravenous' (IV) drug use. The particular way that HIV enters and infects the body is known as the 'route of transmission.'

A route of transmission can be thought of as a pathway that the virus takes from one place in the body (the site of exposure) to another (the bloodstream that then carries HIV throughout the body). Each pathway has immune defenses that try to act against HIV and other infections. These can be thought of as border checkpoints and patrols designed to protect against foreign invaders.

Each route of HIV transmission has a different set of physical barriers and immune defenses, including immune cells and antibodies. These are tailored to different locations in our body. We can see and feel the differences in the physical barriers. The lining of our mouth, for example, is different from the skin on our arm. The differences we can't see with the naked eye include variations in the type and amount of immune defenses located at different sites in the body. There are also variations in the immune defenses found in women and men, and adults and children. By themselves, these defenses are not enough to prevent HIV infection every time a person is exposed to the virus. This is why there is an urgent need for an effective, preventive AIDS vaccine.

Implications for vaccines

The ultimate goal is to develop an AIDS vaccine that prevents HIV infection no matter how someone is exposed to HIV. This is a challenging task since it is possible that the route of transmission will have an effect on how well a vaccine protects against HIV infection and disease.

A comparison of sexual versus IV routes of transmission shows why this is possible. Sexual transmission occurs across 'mucosal surfaces.' These mucosal surfaces are the boundaries between the outside world and the inside of the body, and include the inside of the mouth and nose, the lungs, the lining of the stomach, the vagina and the rectum. For infection to happen during sex, HIV must pass the physical barrier of the mucosal surface as well as the immune cells and antibodies that patrol that surface. Breastfeeding transmission of HIV also happens across mucosal surfaces—the lining of the baby's mouth and stomach.

A syringe that pierces the skin bypasses the physical barrier and immune defenses designed to keep out foreign invaders. When intravenous drug users (IDUs) share syringes that contain HIV-infected blood, a small amount of the virus is injected directly into their bloodstream. Once the virus is in the bloodstream it can spread rapidly throughout the body.

"We cannot assume that vaccines which prevent or reduce sexual transmission will necessarily work as well against spread through IV drug use," says Chris Beyrer, a researcher on vaccines and IDUs at Johns Hopkins University (US). This is not because IDUs will make different immune responses from other people. Most people who are vaccinated with an effective AIDS vaccine will make similar types of immune defenses. But these defenses may be more or less able to block HIV infection depending on the route of transmission of the virus.

There may also be variations in vaccine effects with different types of sexual exposure, such as anal and vaginal sex. The only way to find out how routes of transmission affect vaccines is to test AIDS vaccines in communities where HIV-negative people are likely to be exposed to HIV through different routes, such as gay men exposed through anal sex and IDUs exposed through drug use. This strategy was used in the two large-scale 'Phase III' trials of an AIDS vaccine called AIDSVAX. In the US, Canada and Europe the trial tested the vaccine in just over 5400 people: 5108 HIV-negative men who have sex with men, and 309 HIV-negative women who were at high risk of heterosexual exposure. In Thailand the trial tested a closely-related version of the vaccine in roughly 2500 HIV-negative intravenous drug users. (The vaccine provided no overall protection in the North AmericanEuropean trial; data from the Thai trial was not available as of October 2003.)

Today the need for vaccines that protect against sexual and IV transmission is greater than ever. There is a serious epidemic underway in intravenous drug users in Eastern Europe and Central Asia and the rate of new infections remains high in sub-Saharan Africa, where heterosexual contact is the most common route of transmission. It is crucial to conduct trials in people at risk for infection either via sexual contact or IV drug use. To do this, trial sponsors, governments and communities will have to work together to create research environments that are safe and welcoming to all people, including individuals who are discriminated against because of their behaviors, such as drug users and commercial sex workers. These trials will bring the world closer to the ultimate goal of a universal AIDS vaccine.