A study has revealed that understanding the method of how antibodies work as a vaccine to deactivate a pathogen may have implications for future efforts to design an HIV vaccine.
"This study is part of the effort to understand how protection against HIV occurs," says Dennis Burton, a professor at The Scripps Research Institute. "If we really understand this, then we can design tailor-made vaccines in a way that has never been done before," he added.
The study has been done by Scripps Research scientists and was published on September 6, 2007, in the journal Nature. Keeping this in mind, Burton and his fellow scientists created a mutated version of b12 antibody, which is one of the rare antibodies that protects against the HIV virus, to see the effect of changes that occur in the antibody's effectiveness.
Burton, Scripps Research Professor Carlos Barbas III, and their colleagues first identified b12 antibody in 1992. It originally came from the bone marrow of a 31-year-old male who had been HIV positive without symptoms for six years. "Hopefully, we can work backwards towards a vaccine, using b12 and the very few other really great, broadly neutralizing antibodies against HIV that have been found," says Scripps Research Senior Research Associate Ann Hessell.
The new study revealed that antibodies are extremely significant for effective protection against both infected cells and free virus as the protection depends upon the ability of antibodies to interact with immune cell Fc receptors. Fc receptors helps in the functioning of antibodies against other diseases and are found on the surface of immune cells, such as natural killer cells.
The Fc receptor combines itself with the Fc region of an antibody after an antibody combines with a pathogen, so that the immune system can attack the pathogen. The team of scientists observed the capacity of the two antibodies mutated from b12, named KA and LALA, to prevent infection using the SHIV/macaque model.
In this model, macaques are challenged with a hybrid human-simian virus that infects the model but is recognized by human antibodies. The KA antibody contained a change that prevented it from interacting with the complement cascade, which is a major element of the immune system for destruction of attacking pathogens. The LALA antibody contained a change that rendered it unable to interact with either the complement pathway or the Fc receptor.
In both changes, the place where the antibody combines with free-floating virus was unchanged, allowing the researchers specially to examine the importance of the complement cascade and Fc receptor system for prevention of the infection. "We saw that the KA antibody, which could still bind to the Fc receptors on the immune cells but not to the complement cascade, protected the animals from becoming infected just as the wild type b12 antibody," says Hessell.
"In contrast, the LALA group became infected much like the controls," he added. The results of the examinations proved that Fc receptor plays a key role in preventing HIV infection, not the complement cascade.
In addition to this, In vitro experiments proved that the wild type and KA antibodies blocked the spread of infection more effectively in the presence of other effector cells of the immune system not the LALA antibody.
"Our results are fully consistent with the antibody doing two jobs," says Burton. "Job one, stick to the virus; job two, recruit immune cells to come and kill infected cells," he added.