Antibody-Based HIV Protection Developed for Macaques

Dennis Burton, PhD

New research has established potentially important criteria that could serve as goal posts as researchers continue to work towards a vaccine for HIV.

Scientists from the Scripps Research Institute, in California, say they have been able to protect rhesus macaques monkeys from infection with simian-human immunodeficiency virus (SHIV) using a developmental vaccine. The protection was only temporary, but the experiment suggests that a vaccine could successfully prevent infection with HIV if it were able to meet and sustain certain conditions.

The research also gives investigators clearer targets of the levels of neutralizing antibodies that would be necessary in order to achieve protection against HIV infection. In the new study, investigators at Scripps built upon earlier research with the goal of inducing the body to create a specific kind of neutralizing antibodies.

"We found that neutralizing antibodies that have been induced by vaccination can protect animals against viruses that look a lot like real-world HIV," said Dennis Burton, PhD, chair of Scripps’ Department of Immunology and Microbiology, in a statement.

The team built their strategy around the idea that HIV could be successfully attacked if antibodies bound themselves to the outer envelope protein trimer of the virus. The goal, then, was to produce such antibodies in the lab, and then train the patient’s body to produce more of the same.

They found that by exposing the patient’s immune system to the trimer, the patient’s immune system would recognize the vulnerability in HIV and respond with appropriate antibody production.

In order to make that happen, the investigators leveraged a technique developed at Scripps back in 2013 to engineer trimers that are highly stable. This was important because HIV protein trimers tend to be unstable, and therefore tend to fall apart when isolated.

Using the five-year-old strategy, the team was able to insert the more stable HIV envelope trimers into a vaccine that had previously been used at the institute.

To study the impact of the new trimers, researchers picked 6 macaques that had responded to a previous round of vaccination by developing low levels of antibodies, and 6 macaques that had developed high levels of antibodies following the earlier round of vaccinations.

The macaques were then exposed to a Tier-2 form of SHIV. Tier 2 was chosen because, like human HIV, it is particularly difficult to neutralize. The animals with low titers quickly became infected with SHIV, but the animal with high titers were protected from infection, though the protection was only temporary.

Matthias Pauthner, PhD, a Scripps research associate, said this finding is an important landmark.

“Since HIV emerged, this is the first evidence we have of antibody-based protection from a Tier 2 virus following vaccination," he said in a statement. However, he noted that this study is essentially a proof of concept study, and many important questions remain.

"One question now is how can we get such high titers into every animal?" he said.

Now, Burton, Pauthner, and colleagues have a sense of the level of titers necessary to protect against HIV, though they still need to figure out how to maintain high-enough levels of titers to provide long-lasting protection from HIV infection.

The study, “Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers,” was published online in the journal Immunity.