HIV Poses as E. Coli to Confuse Immune Defenders

Progress toward an HIV vaccine continues to chug slowly down two separate tracks.

Researchers published recent findings on incremental progress toward a vaccine in two academic journals. In a paper appearing today in Cell Host & Microbe, a team led by Dr. Barton Haynes at the Duke Human Vaccine Institute shows how gut flora influences the way a person's immune system responds to HIV.

It explains why antibodies that rise up to fight HIV don’t stand a chance against the virus. Researchers know that when HIV sets up shop in the body it begins reproducing in the gut. The body usually fights new infections by releasing a type of B-cell that takes a sort of mental snapshot of the intruder so it knows how to fight it the next time it appears.

But when HIV arrives in the gut, a group of B-cells that have already been programmed to fight bacterial infections like E. coli respond instead. The reason? The so-called gp41 region of the HIV virus’ outer envelope appears to mimic a bacterial infection like E. coli. The immune system uses the wrong weapon against HIV because the crafty virus has disguised itself as something else.

“It’s the host’s interaction with the virus that defines the outcome,” Haynes told Healthline. “The virus has learned all the host’s secrets and gets around them.” 

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Immune Responses Differ Person to Person

Research at Duke, part of the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), had focused on creating a vaccine using broadly neutralizing antibodies. This has proven elusive, as Haynes recently wrote in a paper published in Science.

CHAVI-ID has received $426.6 million from the National Institutes of Health. CHAVI-ID research also is taking place at the Scripps Research Institute. Its most promising result has come in the form of a vaccine called RV144, which has shown modest success (31 percent efficacy) in a clinical trial of 16,000 adults in Thailand.

The research at Duke is now focused on the lineage of B-cells. But work continues elsewhere building on the hopes raised by RV144.

Research published Aug. 8 in the Journal of Clinical Investigation shows that a person’s genes influence their response to HIV vaccination. The authors, from the Fred Hutchinson Cancer Research Center, showed that only individuals with a specific form of the FCGR2C gene were protected by the RV144 vaccine.

Differing immune responses against a virus that is a master of disguise has made it extremely difficult for researchers to develop a universal vaccine.

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“The reason we haven’t been successful is that for 20 years we’ve had a structural problem,” Haynes said. “All these antibodies we are trying to induce are unusual. All have traits specially controlled by the host immune system.”

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Haynes compares the work of CHAVI-ID to the Manhattan Project, the Human Genome Project, or the CERN supercollider. “With those three, you had the enabling technology. It was a technological feat but we knew how to do it,” he said.

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CHAVI-ID, Haynes said, was a project for which there was no enabling technology. “Could you do a big science project and do discovery to learn the enabling technology? That is what CHAVI provided. It taught us exactly what the vaccine needed to do,” he said.

Some have questioned whether all the money funneled toward vaccine research is worth it. But others counter that we never will treat our way out of HIV. The antiretroviral drugs that keep people alive are expensive and can be toxic over long periods of time.

Though we are still years away from a vaccine, the new Duke research gives scientists like Haynes important information about how the virus operates.

“Is the glass half empty or half full?" Haynes asked. "I tend to be an optimist.”

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