With all the progress that has been made in the fight against HIV/AIDS, including the identification of the virus and its modes of transmission; a reliable test; and, widespread prevention campaigns, one crucial element to stopping its spread remains elusive: a preventive vaccine. In 2004, an estimated 40 million people worldwide were living with HIV, and an estimated 14,000 became infected with HIV every day. If discovered, a preventive vaccine (for use in HIV-uninfected people) could halt new HIV infections and eventually stop the virus from spreading so rapidly. However, an HIV vaccine of any kind remains one of the biggest medical puzzles in history, with many years and many millions of dollars of research producing no effective vaccine.

Vaccines 101

We all have painful memories of getting our shots as kids; all of those were vaccines against different diseases such as tetanus, measles, mumps, and other once-common illnesses. Anyone who has traveled extensively may have also received vaccines to prevent picking up any diseases that are common overseas.

Vaccines are safe and effective ways to prevent illnesses that would otherwise kill or debilitate millions of people. Not only that, but preventing a disease with a vaccine can save millions of dollars compared to treating a disease once it has occurred. The invention of the vaccine has been one of the greatest human accomplishments in the last 100 years.

Preventative vs. Therapeutic Vaccines

A preventive HIV vaccine is different from a therapeutic vaccine. A preventive vaccine would be used by HIV-uninfected individuals to prevent infection, while a therapeutic vaccine would be used by HIV-infected individuals to help boost the immune system.

In the most general scenario, a preventive vaccine introduces a foreign substance into a person’s body so that the body learns how to respond to and fight a specific invader. That way, if the person were exposed to a real threat later on, the body would fight it immediately.

In the case of HIV vaccines currently in development, scientists may take small parts of the HIV virus, change them in a laboratory, and create synthetic copies. The experimental vaccines do not use whole or live HIV, so the vaccines cannot infect a person with HIV or AIDS.

How Vaccines are Developed and Tested

In order for a new vaccine to be approved for use, it must be proven effective by going through a rigorous process of study. Generally, study of an experimental vaccine is done in phases:

• Phase I trials test the vaccine in a small number of humans, usually including less than 50 participants. This is the first time the vaccine will be tried in humans after extensive animal studies. The main goal of a Phase I trial is to test that the vaccine is safe, to see what the side effects might be, and to see—on a preliminary basis—whether it might actually provoke the immune response needed to fight the virus. If the vaccine is proven to be safe, it moves on to Phase II.
• Phase II trials test the vaccine on more people than the Phase I trial—in some cases up to several hundred people. In Phase II trials, the vaccine is further tested for safety/side effects. The immune response to the vaccine is also studied in greater detail. Different doses and administration schedules of the vaccine are also studied in Phase II trials. If the vaccine continues to seem safe and seems effective, it will advance to Phase III testing.
• Phase III trials look at the most promising of the experimental vaccines. In this phase, a preventive vaccine would be studied to see whether it would prevent infection in non-infected people, or perhaps delay, prevent, or diminish illness after infection. Thousands of people are enrolled in this phase and the trial may last several years. If there is sufficient evidence that the vaccine works, and if its safety profile looks good, the vaccine can be approved for widespread use.

The entire process can take up to 10 years and requires many types of participants so that it can be shown that the vaccine works in different groups of people. It is an enormously expensive endeavor. After the U.S. Food and Drug Administration (FDA) approves a vaccine, the vaccine will continued to be monitored for safety and effectiveness in widespread use (sometimes referred to as Phase IV).

While this process sounds straightforward, HIV vaccines have proven to be more complicated. Preventive HIV vaccine trials are conducted in people who are not infected with HIV. However, if they have received the vaccine and it produces an immune response, they may actually “test positive” for HIV on the standard HIV (ELISA) test, even though they aren’t actually infected with the virus.

What the test is picking up and reading as “positive” is actually the presence of HIV antibodies. Antibodies are the body’s customized alarm system for identifying different infections. The body makes specific antibodies for each kind of infection. A different HIV test, called the Western Blot test, can distinguish whether a person is truly HIV infected (due to standard HIV transmission routes) or just testing positive because the vaccine is causing his or her immune system to create antibodies.

HIV Vaccine Progress

HIV vaccine trials are taking place all over the world and are being conducted by many agencies. Most are in Phase I or II trials. Of the few Phase III trials that have been completed, none have come up with an effective vaccine. What they have shown, however, is that Phase III trials can be successfully completed, meaning that more Phase III trials are on the way. There are a few Phase III trials taking place right now.

A Clever Foe

There are a few reasons directly related to the HIV virus as to why discovering an effective HIV vaccine has been difficult.

First, HIV targets the immune system. The body needs a functioning immune system to mount a response to any foreign invaders. The main idea behind a vaccine is to prepare the immune system for an attack, but HIV comes in and begins to destroy the immune system’s ability to function. A vaccine would have to be very effective and create a very strong, lasting immune response to potentially overcome an HIV infection.

Another challenge is that HIV has the ability to change and mutate into different strains, making it resistant to drugs and altogether hard to predict. This means that finding a vaccine that would prevent all strains of the virus would be very difficult indeed.

Essentially, HIV continues to outmaneuver scientists. Until we can find a way to outsmart the virus, it will continue to find ways to change, hide, and spread.

Is There Hope?

There is hope, but it seems like an effective preventive HIV vaccine is still many years away at best. Perhaps the current Phase III studies will succeed. If not, perhaps they will provide a better understanding of how to create an effective vaccine. In addition, by studying those who appear to be more resistant to HIV than others, and those who are infected with HIV but are able to keep the virus at low or non-detectable loads for longer periods of time than average, researchers may be able to tap into clues about HIV immunity and resistance.

Finally, despite the fact that there is no vaccine at present, HIV is still a preventable disease. With proper precautions (such as safe sex, not sharing needles and getting tested regularly), we all can help prevent the spread of HIV.