NIAID To Advance B-Cell Approach To HIV Vaccines

Armen Hareyan's picture


In the immune system, B cells recognize key parts of microbes, called antigens. Then, in cooperation with T cells, a reaction is triggered that leads B cells to produce antibodies, which can lock onto antigens and sweep them out of the body. HIV is devilishly good at fooling B cells and shielding itself from antibodies or changing its antigenic parts, so antibodies can rarely rid the body of the virus. The new NIAID research program aims to uncover mechanisms that will enable scientists to outwit HIV and stimulate the B-cell production of long-lasting antibodies that can neutralize many strains of the virus.

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"This program reflects our commitment to probe the fundamental science underlying HIV vaccine development," says NIAID Director Anthony S. Fauci, M.D. "The study of B cells and broadly neutralizing antibodies to HIV will answer pressing, basic scientific questions and bring greater balance to our portfolio of HIV vaccine discovery research."

In recent years, investigator-initiated grants supported by NIAID have focused more heavily on T-cell based approaches to preventive HIV vaccines than on B-cell based ones. While B cells make antibodies that target and remove dangerous microbes, T cells kill cells infected by pathogens. Many experts believe a successful HIV vaccine will probably need to activate both T cells and B cells; consequently, NIAID's creation of the new B-cell research program is an important stimulus for HIV vaccine discovery.

Some evidence suggests that the program's goal of eliciting broadly neutralizing antibodies to HIV, although extremely difficult, may be feasible. Scientists have discovered that some HIV-infected individuals naturally but rarely produce broadly neutralizing antibodies to HIV. Giving these antibodies experimentally to nonhuman primates protected the animals from HIV infection after exposure to the virus. Scientists now face the challenge of how to stimulate the human immune system to predictably produce broadly neutralizing antibodies to HIV through vaccination.

Combining experience with innovation, NIAID is awarding the B-cell program grants to four investigators who already have established a body of research on B cells and antibodies in the context of HIV, and to six investigators with less experience in this area who have exceptionally creative ideas. Each grantee's combined expertise in basic immunology and HIV pathogenesis reflects the program's roots in a collaboration between NIAID's Division of AIDS and its Division of Allergy, Immunology and Transplantation. The joint awards by the two NIAID divisions culminate a 14-month planning and implementation process that began in March 2007. Scientific discussions a year later, during the NIAID HIV Vaccine Summit in March 2008, underscored the importance of broadly neutralizing antibodies as a promising approach that merits further investigation.