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Studies advance the understanding of broadly neutralizing antibodies

Antibody (antigen) in ac '~ against harmful to the body element

Antikörper und VirenThree recent studies funded by the National Institutes of Health, just throw more light on broadly neutralizing antibodies, which may play a role in developing an effective vaccine against HIV. Studies have demonstrated techniques to stimulate immune cells to produce antibodies that could stop HIV to infect human cells in laboratory or had the potential to develop into these antibodies, according to the National Institute of Allergy and Infectious DiseasesPress release.

Mers VirusIn the first study,Published in early June 18 editionScienceJoseph Jardine, William Schief, and David Nemazee the Scripps Research Institute and his colleagues created a projected imunógena protein that stimulates B-cells to produce precursors CRP01 antibodies in mice.

In the second study,Also published in Science, Rogier Sanders and John Moore Weill Medical College and colleagues showed that recombinant envelope glycoprotein "trimer" HIV complex can stimulate production of neutralizing antibodies "camxate" in rabbits and monkeys.

Finally, a study by Pia Dosenovic and Michel Nussenzweig of Rockefeller University and colleagues, published in theOn June cell 2015 emission, showed that a sequential approach vaccine "two steps" - using the proteins described in the reports of Sciense - may be able to stimulate the production and maturation of broadly neutralizing antibodies that could work effectively AGAINST HIV.

"Together, the 3 roles represent an important starting point to develop HIV vaccines that can elicit a wide production of neutralizing antibodies in people," the statement said "the NIAID.

Below is an edited excerpt Rockefeller University press releaseDescribing the latest study in more detail:

Robotic immunizations may be the key to HIV vaccine

Robot and shield

18 2015 OF JUNE - the secret to prevent HIV infection lies within the human immune system, but "More-of-25-years-of-search-worm" They have not been able, up to now, to produce a vaccine capable of forming the body to neutralize the virus changing. New research from Rockefeller University, in collaboration with other institutions, suggest a single shot will never do the job. Instead, they found that a series of immunizations can be the most promising route for a vaccine against HIV.

Scientists have thought for some time that several immunizations, each tailored to specific phases of the immune response can be used to generate a special class of combating HIV, a special class of antibodies, called broadly neutralizing antibodies. The findings, published in Cell 18 June and the result of a collaborative effort of Rockefeller, the Scripps Research Institute, Weill Cornell Medical College, and other institutions, provide the first evidence supporting this approach.

"As HIV mutates in a patient, the immune system continuously adapts to these changes. In some patients, this process produces broadly neutralizing antibodies, which are abnormal antibodies that can bind and neutralize a range of HIV variants occurring globally. These are antibodies that we try to motivate with a vaccine, "says co-first author Pia Dosenovic, a post-doctorate in Michel Nussenzweig, Molecular Immunology Laboratory at Rockefeller.

"Our experiments suggest that stimulation of the immune response to specific vaccines at specific times, it may be possible that could mimic this process," says co-first author Lotta von Boehmer, an instructor in clinical investigation Nussenzweig also in the laboratory.

HIV is a virus evil precisely because its continuous mutations make it a difficult target for antibodies, immune foreign proteins that recognize molecules called antigens. But part of the virus can not mutate: the link of the spike protein with the virus which attacks immune cells known as T cells CD4. This part of the virus can not change because, without it, HIV would not be able to attach and infect T cells As a result, it is a key target antigen for a few broadly neutralizing antibodies, which overcome attempts by the virus to protect is vulnerable.

Human blood cell LymphocyteA small number of patients infected with HIV develop broadly neutralizing antibodies naturally as a result of the infection itself. Like all other "autoantibodies", which are produced by one type of immune cell, known as a B cell that undergoes cycles of mutations that refine its ability to generate antibodies with exact precision for a given antigen. In comparison with antibodies against other pathogens such as the influenza virus (flu), these broadly neutralizing antibodies are very different, in part because they have undergone a large number of mutations. Researchers have been working to find a shortcut that triggers the process, but so far, these broadly neutralizing antibodies have been shown to be difficult to be motivated by a vaccine.

But when a fault vaccine, perhaps two or more can be successful. O Rockefeller Research Team tested as two critical variations the HIV antigen has affected the response of B cells when administered early in the course of the immune system, the initial response to infection by HIV, or later during the infection process already established. The study was conducted in mice genetically engineered to produce similar antibodies to human beings.

A group of infected mice had antibodies with specific mutations for HIV spike protein; these represented a specific response of a B cell, active during the early stages of infection. Antibodies were expressed by the other mice containing mutations associated with the development of broadly neutralizing antibodies and therefore stood for a later phase of the infection.

For each scenario, they have tested two types of antigens. First, an antigen was designed to make the critical cell envelope CD4 easily accessible, it was made by William Schief and colleagues Scripps. The second, created by John Moore and Rogier Sanders at Weill Cornell, similar to the natural versions, found in HIV.

Test tube with blood cells, plasma, buffy coat and red blood celFor the first stage, the setting designed showed promise for raising production of the antibody produced by B cells which proliferate and produce antibodies with the main features which represent a preliminary step for the production of broadly neutralizing antibodies. However, the most natural was a more effective antigen, prompting the mice to produce antibodies capable of neutralizing a number of different strains of HIV.

"Antigenic reengineering made it possible for mice with the hybrid immune system to obtain the necessary immune response and yet, the most natural antigen is better when it comes to fine tuning of antibodies," says Von Boehmer.

The implication is that by offering specific antigens at specific times, the immune response can be guided by the stepwise method (translator's note:. After some research I gathered that the entry defines "type of infection" If the method works with the characterization HIV infection which, as known, take different paths in different carriers), through the general process of developing neutralizing antibodies.

"While our results suggest that robotic immunizations can make it possible vaccination against HIV, only now beginning to understand how this sequence works," says Dosenovic. "We know about the beginning and the end, but we know nothing about what should happen in between."

The research was led by Nussenzweig, Zanvil A. Cohn and Ralph M. Steinman Professor, a senior physician, the Rockefeller University Hospital and a Howard Hughes Medical Institute researcher and Schief, a professor at Scripps Research Institute and director of the Initiative vaccines Project International for an AIDS vaccine and the Scripps Center for studies of neutralizing antibody broad spectrum.

In two papers published in June 18Science, researchers who generated the antigens used in this study individually tested us for potential use in vaccines. This team found that could induce the production of antibodies "precursors" with some of the necessary characteristics to recognize and block HIV infection. This study suggests that the antigen could be designed a good candidate as the first of a series of vaccines against HIV. Likewise, in aseparate surveyIn Weill Cornell and colleagues describe the use of native antigens to induce the production of antibodies against a single strain of the virus an important first step in a vaccine.

Originally published inStudies Advance Broadly Neutralizing Antibodies of Understanding Against HIV on Thursday, July 09 2015 by Rockefeller University.

Translated by Claudio Souza and reviewed by Mara Macedo between 13 and 14 July 2015

References

JG Jardine, Ota T, D Sok, WR Schief, Nemazee D, et al. Priming the broadly neutralizing antibody response to HIV-targeting germline using the immunogen. Science. June 18, 2015 (Epub ahead of print).

RW Sanders, M. van Gils, R Derking JP Moore, et al. HIV-neutralizing antibodies induced by 1 native-like envelope trimers. Science. June 18, 2015 (Epub ahead of print).

P Dosenovic, L von Boehmer, The Escolano, Nussenzweig MC, et al. Immunization for broadly neutralizing HIV-1 antibodies in human Ig knockin mice. Cell 161 (7): 1505-1515. June 2015.

Other Sources

National Institute of Allergy and Infectious Diseases. NIAID-Funded HIV Vaccine Research Generates Key Antibodies in Animal Models. Press release. June 18, 2015.

Rockefeller University. Sequential Immunizations Could Be the Key to HIV Vaccine. Press release. June 18, 2015.

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