North­eastern researchers have played a key role in studying how anti­bodies that neu­tralize HIV func­tion are struc­tured, a fur­ther step in ongoing global efforts by sci­en­tists to develop a vac­cine for the pan­demic virus that causes AIDS.

Working under the lead­er­ship of immu­nol­o­gist Ellis Rein­herz of Dana-​​Farber Cancer Insti­tute, Northeastern’s John R. Engen, a pro­fessor of chem­istry and chem­ical biology in the Col­lege of Sci­ence, used mass spec­trom­etry to ana­lyze the 2F5 anti­body, one of sev­eral broadly neu­tral­izing anti-​​HIV anti­bodies that pre­vent the devel­op­ment of AIDS.

Broadly neu­tral­izing anti­bodies are extremely rare when found nat­u­rally. In many cases, anti­bodies raised in the lab may interact but are unable to neutralize.

The researchers, whose results were pub­lished this month in the journal Nature Struc­tural & Mol­e­c­ular Biology, probed this problem.

The recog­ni­tion by this anti­body is com­pli­cated,” said Engen, describing his work to ana­lyze the 2F5 anti­body inter­ac­tion with the HIV pro­tein gp41. “2F5 binds to a por­tion of gp41, a spe­cific pro­tein in the HIV outer lipid wall, then 2F5 phys­i­cally moves. That move­ment is quite impor­tant for the final recog­ni­tion process and to create an arti­fi­cial anti­body that does that move­ment will be quite tricky.”

The paper exam­ines the struc­ture and oper­a­tion of anti­bodies that would play an essen­tial role in an even­tual HIV or AIDS vac­cine. The research was financed and super­vised by the Dana-​​Farber Cancer Insti­tute, the National Insti­tutes of Health and the Col­lab­o­ra­tion for AIDS Vac­cine Dis­covery, which is funded by the Bill and Melinda Gates Foundation.

Engen said the work included some of the most dif­fi­cult and rewarding projects he has been involved in in recent years.

My lab at North­eastern has been doing this mass spec­trom­etry method to look at pro­tein con­for­ma­tion for a long time, and this is one of the more exciting projects because it has to do with looking at dis­eases and how they work,” Engen said.

Engen said Northeastern’s role was part of a larger inter­dis­ci­pli­nary team’s efforts, and it was an impor­tant con­tri­bu­tion that is uniquely suited to North­eastern, given the well estab­lished bio­an­a­lyt­ical exper­tise within the Bar­nett Insti­tute of Chem­ical and Bio­log­ical Analysis and the Depart­ment of Chem­istry and Chem­ical Biology.

We’re really excited to work on col­lab­o­ra­tive projects like this in which dif­ferent exper­tise is brought to bear on a single problem of high impor­tance,” Engen said.