Some of the most important breakthroughs of the past century involved the development of vaccines to protect against viruses: smallpox, polio, hepatitis, human papillomavirus (HPV), and even chickenpox. But one virus remains elusive to those seeking to create a vaccine to guard against it: HIV.
The HIV virus was first isolated in 1985, and it was announced at the time by HHS that, “We hope to have a vaccine ready for testing in about two years.”
Unfortunately, there have been many trials and many roads taken trying to develop a vaccine and there still isn’t a truly effective vaccine available. Why is it so difficult to conquer this disease?
An HIV/AIDS vaccine would theoretically have two goals. It could be administered to healthy individuals to protect them from being infected with the HIV virus. This is what is called a prophylactic vaccine. Most of the many vaccines developed have been for this public health purpose.
Lately, however, vaccines have also become therapeutic tools. Therapeutic vaccines can be used to increase the immune response to fight cancerous tumors, hepatitis B, tuberculosis, malaria, and even the bacteria that cause gastric ulcers.
HIV/AIDS is a good candidate for the use of a therapeutic vaccine. Researchers hope that a vaccine could reduce the viral load. Viral load is the amount of HIV virus in a patient, which often corresponds to the severity of the illness.
Due to the difficulty in developing an HIV vaccine, there are many different strategies being tried:
- Peptide vaccines use small proteins from HIV to trigger an immune response.
- Recombinant subunit protein vaccines use larger pieces of proteins from HIV.
- Live vector vaccines use non-HIV viruses to carry HIV genes into the body to trigger immune response. Smallpox is an example of this method.
- Vaccine combinations use two vaccines, one after another to create a stronger immune response. This is referred to as a “prime-boost” combination.
- Virus-like particle vaccine uses a non-infectious HIV look-alike that has some, but not all, HIV proteins.
It is very difficult to develop a vaccine for HIV, because HIV is a very different virus.
According to Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases, there are several ways that HIV doesn’t fit normal vaccine paradigms:
- The immune system of almost everyone is “blind” to HIV. Effective antibodies to the virus are rare.
- Vaccines typically mimic the immune reaction of recovered patients – there are almost no patients who have recovered from HIV.
- Vaccines protect against disease, not infection, and HIV has a long latent period before disease—AIDS—sets in.
- Most vaccines are killed or weakened viruses: killed HIV is not effective at producing immune response, and any live form of the virus is too dangerous to use.
- Vaccines are usually effective against diseases that are rarely encountered (diphtheria, hepatitis B). People in high-risk groups might be exposed to HIV daily.
- A majority of vaccines protect from exposure through the respiratory or gastrointestinal system. HIV enters most often through genital surfaces or blood sharing.
- Whereas most vaccines are tested thoroughly on animal models, there are no really good animal models for HIV/AIDS available.
In April 2013, one of the latest HIV vaccine studies, known as the HVTN-505 study, was ended. 2,500 people were recruited to be part of the study. A weakened cold virus called Ad5 was used to trigger the immune system to recognize HIV proteins.
The study was stopped when it was determined that the vaccine did not prevent HIV infection or reduce the viral load. In fact, 30 people on a placebo became infected with HIV, but 41 people on the vaccine became infected.
Although there’s no proof the vaccine made people more susceptible to HIV infection, earlier failure of Ad5 in the 2007 STEP study led some researchers to worry that anything that stimulated immune cells to attack HIV may increase the risk of HIV infection, due to the unique way HIV infection targets immune cells.
One of the most successful clinical trials to date has been a US Military HIV Research trial in Thailand in 2009. Known as the RV144 trial, two vaccines were used together: 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 sufficient for wide use of this vaccine combination. But, this success allows researchers to study why there was any protective effect at all. People who were protected had developed antibodies to a target on the HIV envelope protein, called the V1/V2 area. There is research underway that is investigating this development.
A July 2012 report suggests that $845 million was spent on AIDS vaccine research in 2011, and more is being allocated every year. Since 1985, more than 30 candidate vaccines have been tested in 80 clinical trials. There’s been only slow progress toward a workable vaccine. But with each failure, more is being learned that can be incorporated into new attempts.
The latest major vaccine trial involves the International AIDS Vaccine Initiative. Patients are being recruited in London, England and Kigali, Rwanda. This trial uses a live vector vaccine strategy, with the Sendai virus carrying HIV surface proteins. It also uses a combination strategy, with a second vaccine boosting immune response. This trial will take two years to complete and carries the hope of many.