Some of the most important medical breakthroughs of the past century involved the development of vaccines to protect against viruses such as:

  • smallpox
  • polio
  • hepatitis
  • human papillomavirus (HPV)
  • chickenpox

But one virus still thwarts those who want to create a vaccine to guard against it: HIV.

HIV was first identified in 1984. The U.S. Department of Health and Human Services announced at the time that they hoped to have a vaccine ready within two years. Despite many trials of possible vaccines, though, a truly effective vaccine is still not available. Why is it so difficult to conquer this disease? And where are we in the process?

Obstacles to an HIV vaccine

It’s so hard to develop a vaccine for HIV because it’s different from other types of viruses. HIV doesn’t fit typical vaccine approaches in several ways:

1. The immune systems of almost all people are “blind” to HIV. Your immune system, which fights disease, doesn’t respond to the HIV virus. It produces HIV antibodies, but they only slow the disease — they don’t stop it.

2. Vaccines are typically made to mimic the immune reaction of recovered people. However, almost no people have recovered from HIV infection. As a result, there’s no immune reaction that vaccines can mimic.

3. Vaccines protect against disease, not infection. HIV is an infection until it progresses to the disease AIDS. With most infections, vaccines buy the body more time to clear the infection on its own before disease occurs. However, HIV has a long dormant period before AIDS sets in. During this period, the virus hides itself in the DNA of the infected person. The body can’t find and destroy all of the hidden copies of the virus to cure itself. So, a vaccine to buy more time won’t work with HIV.

4. Killed or weakened HIV viruses can’t be used in a vaccine. Most vaccines are made with killed or weakened viruses. Killed HIV doesn’t work well to produce an immune response in your body, though, and any live form of the virus is too dangerous to use.

5. Vaccines are typically effective against diseases that are rarely encountered. These include diphtheria and hepatitis B. But people in high-risk groups for HIV might be exposed to HIV daily. This means there’s more chance for infection that a vaccine can’t prevent.

6. Most vaccines protect against viruses that enter the body through the respiratory or gastrointestinal systems. More viruses enter the body these ways, so we have more experience addressing them. But HIV enters the body most often through genital surfaces or the blood. We have less experience protecting against viruses that enter the body in these ways.

7. Most vaccines are tested thoroughly on animal models. This helps ensure that they’re likely safe and effective before they’re tried on humans. However, no good animal model for HIV is available. Any testing that has been done on animals has not shown how humans would react to the tested vaccine.

8. The HIV virus mutates quickly. A vaccine targets a virus in a particular form. If the virus changes, the vaccine may not work on it anymore. HIV mutates quickly, so it’s hard to create a vaccine to work against it.

Prophylactic vs. therapeutic vaccines

There are two main types of vaccines: prophylactic and therapeutic. Most vaccines are prophylactic, meaning they prevent a person from getting a disease. On the other hand, therapeutic vaccines are used to increase your body’s immune response to fight disease that you already have. They're also considered treatments.

Therapeutic vaccines can help fight:

  • cancerous tumors
  • hepatitis B
  • tuberculosis
  • malaria
  • the bacteria that cause gastric ulcers

An HIV vaccine would theoretically have two goals. First, it could be given to healthy people to protect them from HIV infection. This would make it a prophylactic vaccine. But HIV is also a good candidate for a therapeutic vaccine. Researchers hope that a therapeutic HIV vaccine could reduce a person’s viral load.

Types of experimental vaccines

Researchers are trying many different approaches to develop an HIV vaccine. Possible vaccines are being explored for both prophylactic and therapeutic uses.

Currently, researchers are working with the following types of vaccines:

  • peptide vaccines, which use small proteins from HIV to trigger an immune response
  • recombinant subunit protein vaccines, which use larger pieces of proteins from HIV
  • live vector vaccines, which use non-HIV viruses to carry HIV genes into the body to trigger an immune response (The smallpox vaccine also uses this method.)
  • vaccine combinations, or “prime-boost” combinations, which use two vaccines one after another to create a stronger immune response
  • virus-like particle vaccines, which use a non-infectious HIV lookalike that has some, but not all, HIV proteins
  • DNA-based vaccines, which use DNA from HIV to trigger an immune response

Clinical trial stumble

A recent HIV vaccine study, known as the HVTN-505 study, was ended in April of 2013. It studied a prophylactic approach that used a live vector vaccine. A weakened cold virus called Ad5 was used to trigger the immune system to recognize (and thus be able to fight) HIV proteins. About 2,500 people were recruited to be part of the study.

The study was stopped when researchers found that the vaccine did not prevent HIV infection or reduce the viral load. In fact, 41 people on the vaccine became infected with HIV, while only 30 people on a placebo became infected.

There’s no proof that the vaccine made people more likely to get infected with HIV. However, with the previous failure in 2007 of Ad5 in a study called STEP, researchers grew concerned that anything that caused immune cells to attack HIV might increase the risk of HIV infection.

Hope from Thailand and South Africa

One of the most successful clinical trials to date was a U.S. Military HIV research trial in Thailand in 2009. The trial, known as the RV144 trial, used a prophylactic vaccine combination. It used a “prime” (the ALVAC vaccine) and a “boost” (the AIDSVAX B/E vaccine).

This combination vaccine was found to be safe and somewhat effective. The combination lowered the rate of infection by 31 percent compared to a placebo shot. A 31 percent reduction is not enough to prompt wide use of this vaccine combination. However, this success allows researchers to study why there was any protective effect at all.

A follow-up study called HVTN 100 is now underway in South Africa. It’s testing a modified version of the RV144 regimen. And an exciting larger study, called HVTN 702, will also follow up on RV144. That study will also take place in South Africa and involve about 5,400 people. It’s the first major HIV vaccine trial in seven years. Many people are hopeful that it will lead to our first HIV vaccine. Results are expected in 2021.

Other current trials

A current vaccine trial that started in 2015 involves the International AIDS Vaccine Initiative (IAVI). This trial of a prophylactic vaccine studies people in:

  • United States
  • Rwanda
  • Uganda
  • Thailand
  • South Africa

The trial uses a live vector vaccine strategy, using the Sendai virus to carry HIV genes. It also uses a combination strategy, with a second vaccine to boost the body’s immune response. Data collection from this study is complete, and results are expected in 2019.

Another important approach currently being studied is the use of vectored immunoprophylaxis. With this approach, a non-HIV virus is sent into the body to enter cells and produce what’s called broadly neutralizing antibodies. This means the immune response would target all HIV strains. Most other vaccines only target one strain. The IAVI is currently running a study like this called IAVI A003 the United Kingdom. Results are expected in late 2017.

The future of HIV vaccines

According to a 2015 report, $841 million was spent on AIDS vaccine research in 2014. And to date, more than 40 potential vaccines have been tested. There’s been slow progress toward a workable vaccine. But with each failure, more is learned that can be used in new attempts.

If you have questions about an HIV vaccine or would like to take part in a clinical trial, talk to your doctor. They can answer your questions and let you know about any clinical trials that might be a good fit for you.