Developing Vaccines Against Infectious Diseases
Human antibodies, isolated from HIV-1-infected people, can neutralize the AIDS virus (HIV-1), and protect non-human primates from infection with HIV-1-like viruses. Canada Research Chair Dr. Jamie K. Scott is working to develop vaccines that will stimulate the immune system to selectively produce these neutralizing and protective antibodies.
The scientists in Dr. Scott's lab use a peptide library technology that she developed to identify certain peptides (small protein fragments that bind specifically to the protective antibodies). Their goal is to find peptides that specifically target each neutralizing antibody, and then use the peptides as immunogens that induce the production of each of the targeted antibodies.
Dr. Scott is also working to identify new neutralizing antibodies that are produced early in the immune response against HIV-1 infection, as these antibodies may be easier to target by her procedure.
When individuals are infected with HIV-1, they typically elicit a strong antibody response that neutralizes the virus. These neutralizing antibodies, however, cannot clear the virus and stop the infection once it has begun. Since HIV-1 is highly mutable, it produces variants that can escape the neutralizing antibodies. The immune system then produces a new antibody response, but again, viral mutants arise that escape it. Thus, neutralizing antibodies may help to suppress the virus (until the immune system fails), but cannot clear infection. Broadly neutralizing antibodies, which neutralize most HIV-1 variants, have been isolated from infected people, and these, when administered to non-human primates, protect against infection by viruses that bear the HIV-1 envelope and cause an AIDS-like disease. Passive immunization with these antibodies is the only procedure tested so far that produces sterilizing protection from infection with HIV-1.
Thus, Dr. Scott and her colleagues are working to produce vaccines that target the production of antibodies similar or identical to the protective ones found so far. Their approach to making "designer" immunogens that bind specifically to the protective antibodies has promising implications for the development of vaccines against AIDS, and for other emerging infectious diseases.