After 40 Years, Still Waiting for an HIV Vaccine

By Iva Fedorka

In 1981, researchers described a pneumonia caused by the Pneumocystis carini fungus in five gay men, two of which had already died. In the June 5, 1981 issue of the CDC Morbidity and Mortality Weekly Report, they described this infection that usually occurs only in people who are severely immunocompromised. Scientists would soon discover that the disease, which would later be known as AIDS, was affecting the men’s immune systems.

Three years later, scientists identified HIV, the human immunodeficiency virus. In an April 1984 news conference, U.S. Secretary of Health and Human Services Margaret Heckler promised that a vaccine against HIV would be ready to test within two years.

Two years have turned into 40 — and counting.

The HIV Pandemic

The HIV virus has caused huge losses. As of 2019, it has infected more than 75 million people worldwide and killed approximately 32.7 million. Advances in antiviral treatments have prevented even more infected people from transmitting or dying from HIV.

But an HIV infection never really ends. Its long-lasting effect is one reason why we still don’t have an HIV vaccine. Other reasons include its many variants and its unusual ability to evade the body’s immune system.

HIV Research

Cost has also been an issue. Funding for HIV research has historically been distributed in five-year installments, which makes it difficult to efficiently allocate funds. However, HIV-funded research has contributed to the rapid development of other vaccines, including the COVID-19 vaccines.

The technology used in the Johnson & Johnson vaccine was first developed for HIV because it stimulates a strong immune response. Like previous HIV vaccine candidates, it uses altered common cold viruses as carriers to deliver instructions to cells to produce the viral proteins that trigger the immune system.

“The absence of a good HIV vaccine is not for lack of trying,” said Mark Feinberg, a viral immunologist who is president and CEO of the International AIDS Vaccine Initiative in New York City. “The work that’s gone into HIV vaccine development has been by far the most sophisticated and creative.”

HIV Complexity

The biology of the virus itself has been a factor, including the genetic diversity of HIV viruses found around the world. The virus replicates its genetic blueprint rapidly and creates tens of thousands of new copies a day in a single person. Since each copy has, on average, at least one mutation, a person’s body may house multiple variants. Not all variants are transmissible, but some have a greater transmissibility.

The virus also deploys tactics to escape detection by the immune system. Mutations may occur in the parts of the virus targeted by the immune system and may escape detection that way. The virus can also cover parts of its surface in a layer of sugar molecules that obscure the prime antibody targets.

“The body recognizes these sugars as ‘self,’” said Barton Haynes, an immunologist at the Human Vaccine Institute at Duke University School of Medicine. “Basically, what the virus is saying to our immune system is ‘Sure, you can make a protective immune response, go for it.’ But if the antibodies attack, they’re seen as turncoats and are eliminated. That means the body can’t fight the virus as effectively.”

The lifelong nature of the infection is also significant. Many viruses disappear from the body after being defeated by the immune system. But HIV can insert genetic material into its host’s DNA, which establishes a reservoir in immune T cells. Since T cells normally fight infections, the virus is less detectable by the immune system and safe from medicines.

HIV Vaccine Candidates

Only a small number of clinical trials have been conducted to test potential HIV vaccines in people. Of the six completed trials, only one vaccine effectively prevented infection. Named RV144, it required six shots per participant — four “prime” and two “boost” injections — and lowered the risk of infection by 31.2 percent for vaccinated vs. unvaccinated individuals.

The results from RV144, published in the New England Journal of Medicine in December 2009, suggested that antibodies were critical for reducing the risk of infection. That changed views about the relative importance of T cells and antibodies for protection.

Producing the Right Immune Response

Since some infected people naturally produce antibodies to multiple HIV variants, some vaccine developers still hope to make a vaccine that provides sterilizing immunity. By identifying neutralizing antibodies in HIV-infected people, they hope to better understand how the body created those immune proteins.

Other groups remain focused on infection-fighting T cells. As reported in Science Immunology (March 2021), researchers developed a vaccine to cause specialized T cells to kill any T cells infected with HIV.

If these vaccine candidates show promise, they will be moved into clinical trials and eventually the vaccines will go into people’s arms. After nearly forty years of trying, scientists still see light at the end of the tunnel.