Three recent studies funded by the National Institutes of Health have shed more light on widely neutralizing antibodies that may play a role in the development of an effective HIV vaccine. The studies demonstrated techniques to stimulate immune cells to produce the antibodies that could stop HIV from infecting human cells in the laboratory, or had the potential to evolve to these antibodies, according to the National Institute of Allergy and Infectious Diseases Press release.
In the first study, Posted in 18 June advance edition of ScienceJoseph 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 of Weill Medical College and colleagues have shown that the recombinant glycoprotein of the complex HIV "trimer" envelope can stimulate production of "camxate" neutralizing antibodies in rabbits and monkeys.
Finally, a study by Pia Dosenovic and Michel Nussenzweig of the Rockefeller University and colleagues, published in the On June cell 2015 demonstrated that a "two step" sequential approach vaccine - using the proteins described in the Sciense reports - may be able to stimulate the production and maturation of the 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 release Describing the last study in more detail:
Robotic immunizations may be the key to HIV vaccine
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 long thought that multiple immunizations, each adapted to the specific stages of the immune response, can be used to generate a special class of HIV, a special class of antibodies, called largely neutralizing antibodies. The findings, published June 18 at Cell and the result of a collaborative effort from Rockefeller, Scripps Research Institute, Weill Cornell Medical College, and other institutions, provide the first evidence supporting this approach.
"Because HIV mutates in a patient, the immune system continually adapts to these mutations. In some patients, this process produces broadly neutralizing antibodies, which are abnormal antibodies that can bind to and neutralize a broad range of HIV variants, which occur globally. These are the antibodies we want to try to motivate with a vaccine, "says co-author Pia Dosenovic, a postdoctoral fellow at 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 perverse virus precisely because its continuous mutations make it a difficult target for antibodies, foreign immune proteins, that recognize molecules called antigens. But a part of the virus can not mutate: the binding link of the spike protein, with which the virus attacks immune cells known as CD4 T cells. This part of the virus can not change because without it, HIV would not be able to bind and infect T cells. As a result, it is a key part of the target antigen by some broadly neutralizing antibodies, which have outpaced attempts by the virus to protect is vulnerable.
A small number of HIV-infected patients develops broadly neutralizing antibodies naturally as a result of the infection itself. Like all other "autoantibodies," they are produced by a type of immune cell, known as a B cell, that undergoes mutation cycles that refine their ability to generate antibodies with exact accuracy for a given antigen. Compared with antibodies against other pathogens, such as influenza (influenza) virus, these broadly neutralizing antibodies are very distinct, in part because they have been subjected to a large amount of mutations. Researchers have been working to find a shortcut that triggers the process, but so far, these largely neutralizing antibodies have proven difficult to be motivated with a vaccine.
But when a vaccine fails, maybe two or more can be successful. O Rockefeller Research Team tested how two variations of the crucial HIV antigen have affected the B cell response when given early in immune system evolution, in the initial response to HIV infection, or later during the established infection process. The work was conducted on mice genetically modified to produce antibodies similar to those of humans.
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 tested two types of antigens. The first, an antigen was designed to make the crucial envelope of CD4 cells easily accessible, was made by William Schief and colleagues of Scripps. The second, created by John Moore and Rogier Sanders at Weill Cornell, similar to the natural versions, found in HIV-positive people.
For 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 (Note from the translator: After some research I realized that the entry defines "type of infection." In this case the method works with typing of HIV infection that, it is known, takes different directions in different carriers), through the development process of neutralizing antibodies in general.
"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 published articles 18 of June in Science, the researchers who generated the antigens used in the present study tested them individually for potential use in vaccines. This team found that it could induce the production of "precursor" antibodies with some of the characteristics necessary to recognize and block HIV infection. This study suggests that the projected antigen could be a good candidate, as the first in a series of HIV vaccines. Similarly, in a separate 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 in Studies Advance Broadly Neutralizing Antibodies of Understanding Against HIV on Thursday, 09 July 2015 by Rockefeller University.
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, MJ van Gils, R Derking, JP Moore, et al. HIV-1 neutralizing antibodies induced by 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.
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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