Since HIV was identified as the virus causing AIDS 30 years ago, treatments employing combinations of anti-viral drugs have made living with AIDS possible. Still the ultimate goal, which is AIDS prevention, is unmet, and HIV remains extremely difficult to target with a vaccine.


Left untreated, the HIV virus promotes immunodeficiency by killing T cells and is almost always fatal; however, over the last decades scientists have discovered rare individuals who when infected mount an effective anti-HIV response, meaning that the human immune system can at least recognize the virus. LJI scientist Shane Crotty, Ph.D., believes that by studying immune responses of those rare individuals, he might be able to instill this capacity in the vast majority of us that lack it by vaccination.

A discovery Crotty made several years ago encouraged his optimism: namely, he found that the subgroup of patients that produced potent, high-affinity antibodies to the HIV virus also exhibited very high levels of a rare type of “helper” T cells, called follicular helpers (Tfh). Crotty suspected this was not a coincidence, and time proved him right. He has since defined the molecular basis for why Tfh cells are critical to trigger such a strong antibody response against HIV.

B cells are the body’s antibody-producing cells. Crotty found that before they launch a full-blown antibody response, B cells must undergo a maturation process guided by interaction with Tfh cells. That process not only creates an abundance of B cells generating the effective high-affinity antibodies, but at the same time weeds out B cells that produce suboptimal ones.

Crotty’s research holds great promise because it reveals a variable that may have been overlooked in previous attempts to engineer an HIV vaccine. His work suggests that, to be potent enough to eradicate HIV virus, a vaccine must elicit not only a B cell-dependent antibody response, but also include features that maximize Tfh power. Crotty thinks this principle may be applicable to vaccines targeting other pathogens or even tumor cells.


Shane Crotty, Ph.D.
Klaus Ley, M.D.

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