HIV Vaccine Development

Scanning electron micrograph of HIV-1 budding from cultured lymphocyte. Photo Courtesy of the Public Health Image Library; C. Goldsmith

Developing an HIV vaccine has been plagued by difficulties. When the HIV-1 virus was discovered in 1984, scientists thought that it would be only a few years before one was developed, but it turns out that they were far too optimistic. HIV is incredibly effective at evading the mechanisms targeted by most vaccines. It took over 25 years for HIV vaccine development to see its first hopeful results in a 2009 HIV vaccine Thailand trial.

Most vaccines work by stimulating an antibody response against the disease of interest. These antibodies then allow an individual's immune system to fight off an infection. Normally, the immune system only makes large amounts of antibodies after an infection has taken place. Vaccination allows the antibodies to be made before a person has even been exposed to the disease, so the body will be ready to protect itself when it is actually exposed.

This was the tactic initially used to try to develop a vaccine for HIV. Unfortunately, there was a setback in 1994 when it was discovered that although certain antibodies could protect against "tame" strains of HIV made in the laboratory, they were less effective against strains isolated from people. At this point, a lot of AIDS vaccine research shifted toward stimulating a different form of immunity -- cellular, as opposed to antibody-based, immunity.

In Depth:

Cellular immunity is an important component of vaccine protection. Specifically, vaccines can help the body form populations of cells called cytotoxic T lymphocytes, which are cells that can recognize other cells that have been invaded by a virus and kill them.

These cells also produce chemicals that help fight viruses. Once created, they can be easily resurrected from special memory T cells that are capable of reproducing quickly during an actual infection.

Unfortunately, HIV has evolved many characteristics that make it very difficult to target with an HIV vaccine. It mutates constantly, making it very difficult to target specific viral proteins (because they vary so much). It also infects and kills the very T-cells that are so useful in responding to other viral infections.

HIV also turns down the volume on the system the body uses to tell the immune system it has been infected. Normally when a virus enters a cell, the cell "displays" viral proteins on its surface to let the immune system know there is a problem. HIV reduces production of the MHC molecules that bring the viral proteins to the surface.

Finally, HIV hides out in the body by actually copying its genes into the cells of the immune system. HIV can lurk in inactive lymphocytes or lymph tissue, where it is invisible to antibodies and the other potential attack systems produced by an HIV vaccine. It can hide for years until a particular cell is activated and starts producing virus.

This is one of the reasons why HIV is a lifelong infection and, at present, impossible to cure.

There are many scientific and biological reasons why HIV vaccine development has been plagued with failures. Many people believe that there will never be a vaccine for HIV, but there have been some recent developments that give scientists hope. In 2009, not only did scientists discover that some HIV-negative people in long-term relationships with HIV-positive people have antibodies that seem to protect them during oral sex, there appears to be some success seen in an HIV vaccine trial in Thailand.

In Depth:

It's too soon to know how those studies will affect future research, but for the first time in years some people have real hope that an HIV vaccine could someday be a reality. In the meantime, scientists will continue to focus on other means of prevention. Until an AIDS vaccine is found, individuals need to focus on protecting themselves from infection by smart behavioral choices.

Condoms, when used for oral, vaginal and anal sex, do an excellent job of reducing sexual transmission of HIV. Use of clean needles, and providing needle exchange programs, can reduce HIV transmission among injection drug users. Even transmission during pregnancy, labor, and infancy can be reduced through the use of HIV treatment regimens.

With a reasonable amount of effort and common sense, HIV is mostly a preventable disease. Although developing a vaccine for HIV will be enormously helpful for those individuals who can't or won't take behavioral steps to protect themselves from HIV, it is important to never forget that there are things people can and should be doing to reduce their risk now.


Miedema F. "A brief history of HIV vaccine research: stepping back to the drawing board?" AIDS. 2008 Sep 12;22(14):1699-703.

Walker BD, Burton DR. "Toward an AIDS vaccine." Science. 2008 May 9;320(5877):760-4.

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