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Understanding Partial Efficacy

What is a partially effective vaccine?

It is widely thought that receiving a vaccine against a particular disease-causing agent or "pathogen" provides life-long protection against that disease. Many vaccines do indeed provide high levels of long-lasting protection against disease caused by many pathogens. However, there is no such thing as a vaccine that provides 100% protection, 100% of the time. In this sense, all vaccines are "partially effective." It is important to remember that vaccines are still highly beneficial for individuals and communities. They are the most powerful tools we have for preventing disease worldwide. Understanding "partial efficacy" can help to understand current goals for AIDS vaccines.

What could a partially effective AIDS vaccine do?

The phrase "partial efficacy" can be used in two different ways. The first definition describes a vaccine which does not completely prevent infection by a particular pathogen but does help reduce the severity of disease caused by the pathogen. An AIDS vaccine with this type of efficacy would reduce the severity of HIV disease in vaccinated people who later became HIV-infected through blood or sexual exposure.

The second definition of a partially effective vaccine is one that can protect some people in a population but not others. This is possible because a variety of factors affect our immune systems and, by extension, our ability to respond to a vaccine. Most licensed vaccines are actually partially effective, although they may work for 80 or 90% of a population. Others, like oral cholera vaccine and BCG (against tuberculosis) have lower levels of efficacy but are still beneficial.

It is the first type of partial efficacy—protection against disease, but not infection—that is receiving the most attention in the AIDS vaccine field today. This is because most of the candidates being tested in clinical trials are designed to produce cell-mediated immune defenses (see March 2004 Primer on Understanding the Immune System, Part II), which act against HIV only after the virus has entered the body and infected immune cells. Instead of preventing infection from happening at all, these "vaccine-induced" defenses are likely to improve the immune system's ability to fight HIV once infection has occurred. They would do this by helping to slow viral activity and protect immune cells, especially CD4+ T cells, which are targets for HIV infection. These defenses could also help to control the amount of virus circulating in the body (viral load).

Such a vaccine could have several benefits for the individual. First, it could slow the rate of disease progression following HIV infection. By reducing viral load and helping people preserve their CD4+ T cells the vaccine would allow people to live with HIV for longer periods of time without getting sick. It could also prolong the time until a person needed to start antiretroviral therapy (ARVs). ARVs are generally recommended for people with less than 200 CD4+ T cells per mm3 of blood . Each person reaches this point at a different time after infection; an AIDS vaccine could help extend this time period. ARV therapy must be taken every day for life and a vaccine that allowed people to remain healthy and off ARVs could simplify people's lives and avoid the side effects of daily therapy.

A vaccine that reduced the severity of HIV disease could also have positive effects at the community level. Studies have found that people with high viral loads are more likely to transmit the virus to their partners during unprotected sex or to their infants during pregnancy and childbirth. A partially effective vaccine that reduced viral load might reduce the likelihood that an HIV-infected person would pass the virus on. If enough people were vaccinated, this could help to slow the spread of an epidemic in a given country or community.

How do we find a partially effective AIDS vaccine?

Even without a vaccine, people with HIV usually do not get sick for five to seven years after infection. So to directly observe whether an AIDS vaccine affects disease, studies would have to be conducted for ten years or even longer. To get a more rapid answer, vaccine trial sponsors can look at markers of disease progression like viral loads and CD4+ T cell counts in vaccine and placebo recipients who become infected through high risk contact. They can use these data as an early indication of whether or not the vaccine will have a long-term impact on disease progression or infectiousness.

A vaccine that improved health for people who became HIV-infected would be a major breakthrough. It is possible that such a vaccine would be licensed for use outside of a clinical trial. However even after licensure researchers would continue studies to answer open questions including: How long would vaccine-induced protection last? How much of a reduction in viral load is needed to translate into long-term health benefits for the individual? How much of a reduction in viral load is needed to reduce the risk of transmitting to another person?

Part of a comprehensive response

Once an effective AIDS vaccine has been developed, it will not replace or even reduce the need for comprehensive prevention and treatment programs for HIV. This will be particularly true for partially effective vaccines that reduce the severity of HIV disease in vaccinated people who later become HIV-infected. In fact an AIDS vaccine will be most effective when it is promoted as one of several strategies for fighting HIV. This can be compared to family planning methods such as condoms, hormonal contraceptives and diaphragms. No single method is 100% protective, but used in combination, these methods can provide very, very high levels of protection.

This Primer was adapted from the AIDS Vaccine Advocacy Coalitions' forthcoming AIDS Vaccine Handbook; for more information or to order a copy: www.avac.org.