Understanding the Immune System, Part II

How do AIDS vaccines prepare different parts of the immune system to fight HIV?

The goal of an AIDS vaccine is to produce immune defenses that try to stop HIV infection and disease. There are different ways to try to achieve this goal. This is because the immune system uses several different types of defenses to fight HIV or any other foreign invader or "pathogen" that infects the body. The unique features of these different defenses are helping to guide the design of AIDS vaccines.

Innate and acquired immunity

Our immune system is divided into two broad categories: "innate immunity" and "acquired immunity." Innate immune defenses are the first to respond to any foreign invader that enters the body. These defenses are also called "non-specific" or "non-adaptive" defenses; they are like a security force that patrols the body looking for unusual activity, but not a particular intruder.

Innate defenses can protect the body against some infections, but in many cases additional help is needed from acquired immunity. Acquired immune defenses are activated only after our immune system has "recognized" a particular pathogen. These specific defenses are like police tracking down a known criminal; all of their activities are directed towards a single, specific intruder. There are two branches or "arms" of the acquired immune system: humoral (or antibody-mediated) immunity and cellular (or cell-mediated) immunity (see Immune System Primer, Part 1). These two sets of defenses reinforce each other, and they use different strategies to try to prevent infection or rid the body of foreign invaders.

AIDS vaccines are designed to prepare our immune systems to fight HIV. Since a single vaccine may not be able to stimulate both cellular and antibody defenses, scientists are trying to develop the best possible candidates to stimulate each arm of the acquired immune system.

AIDS vaccines and humoral immunity

Many of today's licensed vaccines, including measles, polio and hepatitis B vaccines, cause the humoral immune system to produce large amounts of antibodies. These defenses are molecules that stick to pathogens and prevent them from infecting cells or doing other damage to the body. It is thought that the antibodies produced by these vaccines play a crucial role in protection from disease.

Humoral defenses are coordinated by B cells which have "receptors" on their surface that allow them to connect with and capture pathogens as they circulate freely in the blood. These receptors also connect B cells to other immune cells, and tell the B cells that there is a new pathogen in the body. The B cell starts to multiply itself and also produce antibodies against the pathogen.

An antibody is shaped so that it attaches perfectly onto a pathogen—the way that a key fits into a lock. There are antibodies that bind to many parts of HIV. Some are called "neutralizing" antibodies because they effectively block the activity of HIV before it infects other cells.

Scientists are now trying to design vaccines that resemble antibody "binding sites" (locks) on HIV. These vaccines aim to teach B cells how to produce HIV-specific neutralizing antibodies that will then be ready to fight HIV if it ever enters the body.

Creating a vaccine that leads to the production of neutralizing antibodies against HIV is a very difficult task. The binding sites on HIV that induce neutralizing antibodies are very well hidden. Some of these sites are exposed briefly, at the moment the virus is infecting a cell; others are masked by an outer protective layer on the surface of the virus. This difficulty is the reason why only a few of the vaccines currently in clinical trials have been designed to stimulate production of neutralizing antibodies.

AIDS vaccines and cellular immunity

Every cell in the body has an outer coating or "membrane." This membrane is studded with small bits of chemical information about the cell, such as what it does or what part of the body it comes from. This information is like a business name on the outside of a building; you can tell what is happening inside the building without entering it.

When a cell has been infected by a pathogen, it puts warning signals on its outer coating—similar to the way a person might lean out of a window and call for help if a building was on fire. Cellular immune defenses respond to these warning signals.

This response starts with CD4+ T cells, which are sometimes called the "generals" of the immune system because they direct many other defenses. CD4+ T cells use chemical messengers called "cytokines" to activate CD8+ "killer" T cells that identify and kill pathogen-infected cells.

Many of the AIDS vaccines in clinical trials today have been designed to prepare cellular immune defenses. Each of these experimental vaccines is designed differently, but all use the same basic strategy: scientists start by manufacturing small molecules that mimic fragments of HIV but cannot cause HIV infection or disease. These fragments are packaged into a vaccine which is delivered into the body (usually via injection). Antigen presenting cells, including dendritic cells (see February 2004 Primer on Understanding the Immune System, Part I), patrol the body and pick up the synthetic fragments and display them on their surfaces, causing CD4+ T cells to respond. The goal is to create cellular defenses that will react quickly and powerfully if HIV ever enters the body.