This illustration shows how the envelope proteins covering the surface of an HIV virion (1, 2) bind to a host cell (3, 4). The trimeric MPER region of gp41 is shown in red and can be disabled by antibodies, shown in light blue

Duke scientists have taken aim at what may be an Achilles' heel of the HIV virus.
Combining expertise in biochemistry, immunology and advanced computation, researchers at Duke University have determined the structure of a key part of the HIV envelope protein, the gp41 membrane proximal external region (MPER), which previously eluded detailed structural description.
The research will help focus HIV vaccine development efforts, which have tried for decades to slow the spread of a virus that currently infects more than 33 million people and has killed 30 million more. The team reported the findings online in the Jan. 13 early edition of Proceedings of the National Academy of Sciences.
"One reason vaccine development is such a difficult problem is that HIV is exceptionally good at evading the immune system," said Bruce Donald, an author and professor in Duke's computer science and biochemistry departments. "The virus has all these devious strategies to hide from the immune system."
One of those strategies is a dramatic structural transformation that the virus undergoes when it fuses to a host cell. The envelope protein complex is a structure that protrudes from HIV's membrane and carries out the infection of healthy host cells. Scientists have long targeted this complex for vaccine development, specifically its three copies of a protein called gp41 and closely associated partner protein gp120.
The authors said they think about a particular region of gp41, called MPER, as an Achilles' heel of vulnerability.
"The attractiveness of this region is that, number one, it is relatively conserved," said Leonard Spicer, senior author and a professor of biochemistry and radiology. In a virus as genetically variable as HIV, a successful vaccine must act on a region that will be conserved, or similar across subtypes of the virus.
"Second, this region has two particular sequences of amino acids that code for the binding of important broadly neutralizing antibodies," said Spicer. The HIV envelope region near the virus membrane is the spot where some of the most effective antibodies found in HIV patients bind and disable the virus.

When the virus fuses to a host cell, the HIV envelope protein transitions through at least three separate stages. Its pre- and post-fusion states are stable and have been well studied, but the intermediate step—when the protein actually makes contact with the host cell—is dynamic. The instability of this interaction has made it very difficult to visualize using traditional structure determination techniques, such as x-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy.
That's where Duke's interdisciplinary team stepped in, solving the structure using protein engineering, sophisticated NMR and software specifically designed to run on limited data.
First author Patrick Reardon spent years engineering a protein that incorporated the HIV MPER, associated with a membrane and behaved just like gp41 in the tricky intermediate step, but was stable enough to study. Reardon, then a PhD student under Spicer, is now a Wiley postdoctoral fellow at the Environmental Molecular Sciences Laboratory, a scientific facility in the Department of Energy's Pacific Northwest National Laboratory.
The result captured the shape of the three-parted MPER in its near-native state, but the protein needed to be more than structurally accurate—it had to bind the broadly neutralizing antibodies.
"One of the most important aspects of the project was ensuring that this construct interacted with the desirable antibodies, and indeed, it did so strongly," Reardon said.
The team validated the initial structure using an independent method of data analysis developed by Donald's lab, which showed alternate structures were not consistent with the data.
"The software took advantage of sparse data in a clever way that gave us confidence about the computed structure," Donald said. It used advanced geometric algorithms to determine the structure of large, symmetric, or membrane-bound proteins—varieties that are very difficult to reconstruct from NMR data.
Donald's lab has been perfecting the method for a nearly decade, and Donald said its application in this paper represents a culmination of that work, demonstrating how the two-pronged approach can illuminate the structure of complex protein systems.
The next steps of this research have already begun. In December, Duke received a grant of up to $2.9 million from the Bill & Melinda Gates Foundation to fund the development of an HIV vaccine that will build on these findings.

The world's first vaccine against smoking has been developed by the company "Selecta (RUS)." Expected in 2018 they arrived at pharmacies, said the site "newsru."

According to Russian scientists, a subsidiary of the large U.S. holding company, it is a means of stimulating the production of antibodies that block nicotine in the blood. To provoke an immune response against the tobacco.

As a result, a person stops experiencing a pleasant sensation of smoking (nicotine can affect the brain).

Thus no point in smoking and it is easy to grips with the psychological addiction.

According to statistics from the World Health Organization (WHO) each year smoking kills about 4 million people.

People do not quit smoking despite injury information on nicotine for smoking bans in public places in many countries and tax increases.

Same group of Russian scientists now developing vaccines against diabetes, hepatitis B and skin cancer.

Meanwhile, a new study of New Zealand scientists shows that smokers are switching to electronic cigarettes to quit the habit have the same chance of success as those using nicotine patches , reported the Associated Press and Reuters .

The first-ever study comparing the efficacy of electronic cigarettes with nicotine patches as standard therapy for smoking.

Scientists from the University of Auckland found that the achievement levels are similar, it is more likely that electronic cigarettes to help their users do to reduce the amount of tobacco you smoke. Moreover, people go to much greater willingness of electronic cigarettes than nicotine patches .

Nicotine degradation before reaching the heart and brain, innovative vaccine greatly reduces dependence on nicotine products, taking away the pleasant effects of their use.

Smoking is a difficult habit to quit. It has been shown that the pharmacological and behavioral aspects of this, there is still a form of legal drugs, are similar to those of addiction to cocaine and heroin. But if you did not initially develop an addiction?

Researchers from the Medical College of Cornell University, New York, have developed a drug that inhibits the effects of nicotine intoxication. Although it is only 0.6 to 3% by dry weight of most tobacco, nicotine is a very potent drug. Once entered in the blood, it needs 10 to 20 seconds to pass the blood-brain barrier. Despite this his speed, nicotine is powerless before the new detergent. The vaccine stimulates the liver to produce significant quantities of antibodies that destroy the nicotine molecule almost as soon as it enters the bloodstream. So totally disappears relaxing and calming effect of a cigarette.

Similar mechanism therapies have long existed, but have a huge disadvantage - including regular, weekly administration of a cocktail of drugs that have very adverse effects and should be combined with immunosuppressants. The new product is applied only once and ensure sustainable long-term effects. The tool can be used both for prevention in young people at risk who would succumb to the habit, and in heavy smokers, have exhausted all other alternatives to combat addiction.

Braasch Biotech announced that they have received the first patent for anti-somatostatin vaccine for the treatment of obesity in dogs and cats. This is the first patent granted for the treatment of obesity by the vaccine.

Happily curious prevalence of obesity among farmers move in parallel with their pets. In the U.S., 52.5% of dogs and 58.3% of the cats are overweight. U.S. veterinarians warn that 80 million dogs at risk of arthritis, diabetes, hypertension and a number of cancers.

Just like in humans, obesity in pets reached epidemic dimensions. Once reached the pathological condition, the animal needs the intervention of the holder in order to revert to a healthy weight. The vaccine is one of the few alternatives other than additional walks in the park. Yet its registration in the European Union, Brazil, Mexico, Canada, the USA and Japan.

Braasch Biotech have an extensive portfolio of anti-somatostatin products for the treatment of a number of metabolic diseases.

In an approach with the potential to aid therapeutic vaccine development, Whitehead Institute scientists have shown that enzymatically modified antibodies can be used to generate highly targeted, potent responses from cells of the immune system.

The approach, referred to as "sortagging," relies on the bacterial enzyme sortase A to modify antibodies to carry various payloads, such as peptides, fluorophores, lipids, fluorophores, and proteins. In this case, the scientists, whose findings are reported online this week in theProceedings of the National Academy of Sciences, attached a variety of small antigens to an antibody directed at the surface of key immune cells. Through sortagging, the scientists were quickly able to prepare various antibody-antigen fusions and to deliver the antigens to their intended targets and track them as the immune cells mounted their intricate responses.

"Sortagging is remarkably specific and efficient," says Lee Kim Swee, a researcher in the lab of Whitehead Member Hidde Ploegh. "We were able to create 50 different constructs (antibody-protein attachments), which wouldn't have been feasible if we had relied on the more traditional approach of genetic fusion."

Swee and colleagues tested the approach in a mouse model of herpes virus, sortagging 19 known viral epitopes to a cell-specific antibody. They created a vaccine cocktail and immunized a group of mice. Upon subsequent re-exposure to the virus, vaccinated mice showed a 10-fold reduction in the amount of circulating virus.

"This is proof of principle that one could in fact use sortagging on antibodies to easily attach a tailored set of antigens, toward which the immune system can be educated," Swee says. "This technique also helps us understand how to design better antibody-based vaccines."

For paper co-author Carla Guimaraes, sortagging's value is bolstered by its flexibility. She likens it to "playing with Legos," because it allows "you to mix and match" proteins of diverse shapes, sizes, and functions. The process can be used, for example, to attach the relatively large green fluorescent protein (GFP) to antibodies without hindering GFP's desirable fluorescing activity or the binding of the conveying antibody to its intended target.

"Imagination is really your only limitation," says Guimaraes, who is also a postdoctoral researcher in the Ploegh lab. "You could for example, use sortase to attach a toxin to an antibody and use that antibody to deliver the toxin to specific cells." Such an approach, she notes, would be an appealing strategy for developing better-tolerated cancer therapies.

Hidde Ploegh's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.