Antibody treatment used by researchers to protect humanized mice from HIV

[Cosmicdancer]

This news was posted in the Treatment News section of Poz, but I figured I'd link to the news in Science Daily.

http://www.sciencedaily.com/releases/2014/02/140211141105.htm

Antibody treatment used by researchers to protect humanized mice from HIV

February 11, 2014

Source: NIH/National Institute of Allergy and Infectious Diseases

Summary:  Scientists have shown that boosting the production of certain broadly neutralizing antibodies can protect humanized mice from both intravenous and vaginal infection with HIV. Humanized mice have immune systems genetically modified to resemble those of humans, making it possible for them to become HIV-infected.

NIH-funded scientists have shown that boosting the production of certain broadly neutralizing antibodies can protect humanized mice from both intravenous and vaginal infection with HIV. Humanized mice have immune systems genetically modified to resemble those of humans, making it possible for them to become HIV-infected.

Led by David Baltimore, Ph.D., of the California Institute of Technology, the investigators inserted the genes encoding the NIH-discovered broadly HIV neutralizing antibody VRC01 into a vector, a virus that infects mice but does not cause disease. In a unique technique known as vectored immunoprophylaxis (VIP), the researchers infected laboratory mice with this altered virus, enabling certain of their cells to produce the antibodies for extended periods. To test the applicability of this approach to human infections, the researchers used a novel method of repeatedly exposing these mice to low doses of HIV in a manner that mimics human sexual intercourse. In two separate experiments, the investigators assessed protection from infection with two strains of HIV: a standard laboratory strain as well as one that is commonly transmitted among humans.

Two of the 10 mice expressing VRC01 antibodies became infected with the laboratory strain of HIV after 13 to 15 exposures to the virus. In contrast, all nine mice without the antibodies were infected with HIV within six exposures. In the second experiment, researchers used a modified form of the VRC01 antibody, known as VRC07, and challenged the mice with an HIV strain known to be heterosexually transmitted among people. The mice expressing the VRC07 antibody were completely resistant to infection during repeated intravaginal challenge. Taken together, these results indicate that VIP can protect mice from infection with strains of HIV that cause human disease and suggest that a similar strategy could be developed to reduce transmission in people, the authors write.

Story Source:

The above story is based on materials provided by NIH/National Institute of Allergy and Infectious Diseases. Note: Materials may be edited for content and length.

Journal Reference:
Alejandro B Balazs, Yong Ouyang, Christin M Hong, Joyce Chen, Steven M Nguyen, Dinesh S Rao, Dong Sung An, David Baltimore. Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission. Nature Medicine, 2014; DOI: 10.1038/nm.3471

[geobee]

Another (short) article.  Dr. Baltimore does the video. 

http://medicalxpress.com/news/2014-02-method-hiv-fighting-antibodies.html

The video is a few years old.  They inject this modified virus into muscle, you start producing antibodies and boom! you're resistant to infection.  It works in mice, at any rate.  Dr. B is careful to say that what often works in mice doesn't work in humans.

I think Dr. Picker's CMV or Dr. B's VIP is going to be what does it.  We're going to need something always producing antibodies.  Trying to clear all the reservoirs -- that seems really tough.  But having soldiers always at the ready seems easier.  I'm a computer programmer, not a scientist, tho!

[Cosmicdancer]

I'm not sure what new findings they've made between the research on mice in 2011 and this more recent news.  It's not clear if they were working on mice with humanized immune systems in 2011 or not, but that's clearly the case in the more recent research.  While the article focuses on the effectiveness of the VIP technique in preventing infection, it seems like it would also have therapeutic potential, perhaps even clearing the reservoir.   

[Dr.Strangelove]

I'm not sure either. Maybe this bit:

We recently demonstrated the ability of vectored immunoprophylaxis (VIP) to prevent intravenous transmission of HIV in humanized mice using broadly neutralizing antibodies10. Here we demonstrate that VIP is capable of protecting humanized mice from intravenous as well as vaginal challenge with diverse HIV strains despite repeated exposures.

So, this time they let humanized female mice get raped by HIV-positive males to see if the immunoprophylaxis protects them from getting infected via vaginal sex?! Those sick scientists... disgusting! 


Seriously though, I find this very promising. What I wonder, though, is why they seem to focus on exploring the potential of this strategy as a immunoprophylaxis first. Wouldn't it be just as useful as a therapeutic vaccine? After all, those exact broadly neutralizing antibodies enable elite controllers to keep their infection in check for many years. Therefore, to me it seems, an application for therapeutic use would be the most straightforward approach to explore first. Or am I missing something?

[Jmarksto]

I'm not sure either. Maybe this bit:So, this time they let humanized female mice get raped by HIV-positive males to see if the immunoprophylaxis protects them from getting infected via vaginal sex?! Those sick scientists... disgusting! 


Seriously though, I find this very promising. What I wonder, though, is why they seem to focus on exploring the potential of this strategy as a immunoprophylaxis first. Wouldn't it be just as useful as a therapeutic vaccine? After all, those exact broadly neutralizing antibodies enable elite controllers to keep their infection in check for many years. Therefore, to me it seems, an application for therapeutic use would be the most straightforward approach to explore first. Or am I missing something?

I wondered the same thing - perhaps it is that funding is more available for prophylactic vaccines as opposed to therapeutic?  I have to imagine that if this does work in humans the therapeutic vaccine would be quick to follow - not to mention that many people would try to take the prophylactic off label.

In another article (I can't remember which publication) on this study the author suggested that this work could earn Dr. Baltimore another Nobel prize - if this works  prophylacticly and therapeuticly he will certainly deserve it.

[Matts]

http://medicalxpress.com/news/2014-08-scientists-boost-potential-passive-immunization.html

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13612.html

Scientists boost potential of passive immunization against HIV

Scientists are pursuing injections or intravenous infusions of broadly neutralizing HIV antibodies (bNAbs) as a strategy for preventing HIV infection. This technique, called passive immunization, has been shown to protect monkeys from a monkey form of HIV called simian human immunodeficiency virus, or SHIV. To make passive immunization a widely feasible HIV prevention option for people, scientists want to modify bNAbs such that a modest amount of them is needed only once every few months.


     

To that end, an NIH-led team of scientists has mutated the powerful anti-HIV bNAb called VRC01 so that, once infused into monkeys, it lasts three times longer in blood than unmutated VRC01, collects in rectal mucosal tissue, and persists there more than twice as long as unmutated VRC01. Concentrating anti-HIV bNAbs at mucosal surfaces of the rectum and vagina, the subject of additional study, is critical for blocking sexual transmission of HIV.

In addition, the scientists found, a low-dose infusion of mutated VRC01 protected monkeys against SHIV infection more effectively than a low-dose infusion of unmutated VRC01.

The mutation works by enhancing VRC01's ability to bind to a cellular protein that prevents the antibody from degrading inside cells and influences how frequently the antibody reaches mucosal surfaces and stays there, the researchers report. This finding may inform antibody-based prevention strategies against not only HIV but also other viruses that invade the body at mucosal surfaces, including rotavirus, poliovirus, norovirus and influenza virus.

Next, the researchers will test infusions of mutated VRC01 in people to learn if it concentrates in mucosal tissues and persists there and in blood for an extended period.


 Explore further: Researchers use antibody treatment to protect humanized mice from HIV

More information: S-Y Ko, et al. Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature, DOI: 10.1038/nature13612 (2014).

[Jeff G]

I have never heard the term humanized mice . I rarely read these threads but I did this one and its very interesting even though I had a squeaky mouse voice in my head saying oh no you didn't just inject me with aids .   

[OneTampa]

Interesting.  I wonder what Mighty Mouse would say about this?

 

[xman]

It works in mice, at any rate.  Dr. B is careful to say that what often works in mice doesn't work in humans.

this is why we waste years of research on animal testing. to see finally that it doesn't work on humans. i understand brief testing for safety issues but even toxicities can differ from animals to humans. sometimes i imagine how an alien intelligence may see our species desperately and quite inefficiently trying to fight terrestrial diseases. 

[tryingtostay]

Dang I should of been a research scientist!