DNA-based HIV vaccine produces critical tier-2 neutralizing antibodies in mouse model

Previous attempts at making HIV vaccines elicit an important antibody response have often required long experiments in large animal models. Now, researchers say they've been able to produce the prized tier-2 neutralizing antibodies in mice. 

Tier-2 neutralizing antibodies are the kind needed for the most common strain of the 41-year virus. It had previously taken large animals, including nonhuman primates, to show an HIV vaccine could induce these antibodies, researchers at the Wistar Institute said. 

The scientists were able to deliver a DNA vaccine that led to tier-2 neutralization in mice for the first time. The findings, published this month in Nature Communications, could lead to "more advanced HIV vaccine concepts," said Wister's Daniel Kulp, Ph.D., corresponding author on the research, in a statement

The Wistar team encoded a native-like trimer—proteins that mimic the structure of the spike target for antibodies—into DNA that was delivered into mice. The researchers said this delivery method aims to turn host bodies into "antigen factories." They also tested a standard protein immunization on another set of mice. 

While both groups of mice had strong immune responses, only the mice that were given the DNA-encoded trimer were able to form tier-2 neutralizing antibodies, the researchers said. 

Researchers then isolated monoclonal antibodies from the mice to look at the atomic blueprint of one of the tier-2 neutralizing monoclonal antibodies. The team found that the antibody binds to a segment of the protein, dubbed C3V5, that prompts the immune response. Previous studies have shown antibodies binding to that region are able to protect animals from a close relative of HIV in nonhuman primates, known as SHIV.

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“The structure gives us incredible insight into how this antibody is able to neutralize the virus. For the first time, we can strategize about how to design new vaccines that can generate broadly neutralizing antibody responses to the C3V5 epitope," Kulp said. 

Using DNA vaccines, in which nucleic acids are delivered to help the host produce antigens for an immune response, could also help reduce the cost and time it takes to make and test new HIV vaccines, the researchers said. More than 40 years into the HIV epidemic, there is no approved vaccine, so cost and speed are of increasing interest.

Other recent developments in HIV research include a study showing Merck's blockbuster cancer med Keytruda helped flush dormant parts of the virus out of immune cells. Those findings could lead to new treatment options as current meds for people with HIV require a daily regimen for the remainder of a patient's life. 

On the vaccine side, Moderna is testing its messenger RNA technology, spotlighted during the pandemic, for a vaccine to stave off HIV. 

Excision BioTherapeutics also began testing its CRISPR-based therapy last month after animal studies found it was able to clear the virus from mice.