March for Science ATL: photos

Emory scientists and supporters of science were out in substantial numbers Saturday at the March for Science Atlanta in Candler Park. March organizers, many of whom came from the Emory research community, say they want to continue their advocacy momentum and community-building after the event’s Read more

How race + TBI experience affect views of informed consent

The upcoming HBO movie of The Immortal Life of Henrietta Lacks reminds us that biomedical research has a complex legacy, when it comes to informed consent and people of color. A paper from Emory investigators touches on related issues important for conduct of clinical research Read more

Fecal transplant replants microbial garden

Emory physicians explain how FMT (fecal microbiota transplant) restores microbial balance when someone’s internal garden has been Read more

functional cure

Clues to how anti-integrin antibody suppresses SIV

In October 2016, Emory and NIAID researchers published results in Science that surprised the HIV/AIDS field.

They showed that treatment with an antibody, on top of antiretroviral drugs, could lead to long-term viral suppression in SIV-infected monkeys. A similar antibody is already approved for Crohn’s disease, and a clinical trial has begun at NIAID testing the effects in people living with HIV.

The HIV/AIDS field is still puzzling over a study led by Emory pathologist Tab Ansari.

All that was achieved even though HIV/AIDS experts are still puzzled by how the antibody works. Last week, Christina Guzzo,with NIAID director Anthony Fauci’s lab, presented new data at the Conference on Retroviruses and Opportunistic Infections in Seattle that provide some clues. But the broader issue of “what is the antibody doing?” is still open.

Let’s back up a bit. The antibody used in the Science paper targets a molecule called integrin alpha 4 beta 7, usually described as a “gut homing receptor” for CD4+ T cells, which are ravaged by HIV and SIV infection.  Study leader Aftab Ansari (right) and Fauci have both said their idea was to stop T cells from circulating into the gut, a major site of damage during acute viral infection.

Integrin alpha 4 beta 7 was also known to interact with the HIV envelope protein. Accordingly, it is possible to imagine some possibilities for what an antibody against integrin alpha 4 beta 7 could be doing: it could be driving T cells to different places in the body or affecting the T cells somehow, or it could be interfering with interactions between SIV and the cells it infects.

The new data from NIAID say that integrin alpha 4 beta 7 is found on the virus itself. This finding makes sense, because SIV and HIV are enveloped viruses — they steal the clothes of the cells they infect and emerge from. [Integrin alpha 4 beta 7 also appears to help the virus be more infectious in the gut, Guzzo’s presentation says.]

So a third possibility appears: the anti-alpha 4 beta 7 antibody is mopping up virus. Perhaps it’s acting like a virus-neutralizing antibody or the anti-CD4 antibody ibalizumab — CD4 is the main viral receptor on T cells. It could explain why the anti-integrin antibody’s effect is so durable; HIV/SIV can mutate to escape neutralizing antibodies directed against the viral envelope protein, but it can’t mutate the clothes it steals! Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Access to HIV’s hideouts: T cells that take on their own

Police procedural television shows, such as Law + Order, have introduced many to the Internal Affairs Bureau: police officers that investigate other police officers. This group of unloved cops comes to mind in connection with the HIV/AIDS research published this week by Rama Amara’s lab at Yerkes National Primate Research Center and Emory Vaccine Center.

“Killer” antiviral T cells (red spots) can be found in germinal centers. The green areas are B cell follicles, which HIV researchers have identified as major reservoirs for the virus. Image courtesy of Rama Amara.

HIV infection is hard to get rid of for many reasons, but one is that the virus infects the cells in the immune system that act like police officers. The “helper” CD4 T cells that usually support immune responses become infected themselves. For the immune system to fight HIV effectively, the “killer” CD8 antiviral T cells would need to take on their own CD4 colleagues.

When someone is HIV-positive and is taking antiretroviral drugs, the virus is mostly suppressed but sticks around in a reservoir of inactive infected cells. Those cells hide out in germinal centers, specialized areas of lymph nodes, which most killer antiviral T cells don’t have access to. A 2015 Nature Medicine paper describes B cell follicles, which are part of germinal centers, as “sanctuaries” for persistent viral replication. (Imagine some elite police unit that has become corrupt, and uniformed cops can’t get into the places where the elite ones hang out. The analogy may be imperfect, but might help us visualize these cells.)

Amara’s lab has identified a group of antiviral T cells that do have the access code to germinal centers, a molecule called CXCR5. Knowing how to induce antiviral T cells displaying CXCR5 will be important for designing better therapeutic vaccines, as well as efforts to suppress HIV long-term, Amara says. The paper was published in PNAS this week. Read more

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SIV remission follow-up

The surprising finding that an antibody treatment can push SIV-infected monkeys into prolonged remission, even after antiviral drugs are stopped, continues to rumble across the internet.

siv-a4b7-teaser-copy

Blue circles show how viral levels stayed low even after antiretroviral drugs were stopped.

The Science paper was featured on NIH director Francis Collins’ blog this week. NIAID director Anthony Fauci has been giving presentations on the research, which emerged from a collaboration from his lab and Tab Ansari’s at Emory. Fauci’s talk at the recent HIV prevention meeting in Chicago is viewable here.

At Lab Land, we were pleased to see that the watchdogs at Treatment Action Group had this to say:

“Media coverage of the paper has generally been accurate, but has had to wrestle with the uncertainty that exists among scientists regarding how ART-free control of viral load should be described.”

HIV pioneer Robert Gallo noted in an article accompanying the Science paper that the anti-integrin antibody treatment represents an emerging alternative to the vaunted “shock and kill” strategy, which he termed “soothe and snooze.” Note to reporters: the upcoming “Strategies for an HIV cure” conference at NIH in mid-November might be a good chance to compare the different strategies and put them in perspective.

Read more

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Background links on SIV remission Science paper

This was the first consistent demonstration of post-treatment immune control in monkeys infected with SIV, without previous vaccination. Long-term post-treatment control of HIV has been reported in only a handful of people treated soon after infection. To learn more, check out these links.

Transient SIVmac remission induced by TLR7 agonist, reported at 2016 CROI conference

Immune control of SIVagm, no antiretroviral drugs necessary. Model of “elite controllers.”

Immune clearance of SIVmac; prior CMV-based vaccination necessary.

Post-treatment control of HIV – VISCONTI study. Roundup of HIV remission cases, from Treatment Action Group. Read more

Posted on by Quinn Eastman in Immunology Leave a comment