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Fruit of Recent Retreat

Nabel Outlines Plans for Vaccine Center

By Rich McManus

On the Front Page...

Dr. Gary Nabel, new director of the Vaccine Research Center, compared the VRC organizational structure — a recent invention of his — to both a company with a board of directors and to University of Michigan football at an hour-long presentation before NIH's AIDS vaccine research committee (AVRC) on May 5.

Continued...

A professor of internal medicine and biological chemistry at Michigan before his arrival here in mid-April, Nabel spoke on the third and final day of an AVRC workshop titled, "New Concepts in HIV Vaccine Development" that drew hundreds of scientists from around the world to the Natcher center; sessions were devoted to vaccine modalities, immunity, use of animal models in vaccine development, new assays to develop and test HIV vaccine candidates, and other topics.

Nabel's role on the agenda was to relate what went on at a retreat he held in mid-April where 30 or so authorities in the field brainstormed for a day and a half on how best to craft an effective VRC. His "offensive line," and the people with whom he has worked most closely during his brief tenure so far, is an executive committee consisting of NIH director Dr. Harold Varmus, the directors of the two VRC-sponsoring entities — NCI (Dr. Richard Klausner) and NIAID (Dr. Anthony Fauci), Office of AIDS Research director Dr. Neal Nathanson, and NIH deputy director for intramural research Dr. Michael Gottesman. "They have been delightful to work with," Nabel noted.

Below this leadership group on the organizational chart is an external advisory committee ("the coaches"— not yet formally linked to the AVRC, chaired by Dr. David Baltimore), a board of scientific counselors, then Nabel in the director's office. He envisions four groups reporting to him: basic sciences (further subdivided into immunology, primate models and virology), translation (assay development, vector optimization), clinical sciences (human immunology, clinical virology), and core laboratories (a biosafety level-3 lab, a GLP [good laboratory practices, a certification standard] lab, and a lab specializing in immune assays). And the good news for those hungry to do AIDS vaccine research is that Nabel is anxious to fill this structure with about 100 people who are "scientifically outstanding, highly collaborative, and have a passion for creating vaccines.

"There are many places that emphasize just scientific excellence," said Nabel, "but the VRC wants people with all three characteristics. The chemistry of everyone involved is really going to be key. I'm really looking forward to putting people and approaches together."

Nabel said he's had some fun designing not only the organizational blocks of the VRC, but also the building itself. Recalling the pleasure of combining meals with scientific chats during his postdoctoral training at the Whitehead Institute, he described a "cyber café" to be built on the first floor that will combine library resources with a café; the eating area will be connected via a spiral staircase to a balcony where journals and Internet-ready computers will be available. Showing architectural drawings of a typical lab floor, he cited such embellishments as high, arched windows, conference space and open labs that "should make the VRC a fun place to work."

Offering a synopsis of the Apr. 16-17 retreat, which included seven sessions and "represents the collective effort of many people," Nabel said the VRC mission is to "facilitate development of effective vaccines for human disease, mainly AIDS." He described three goals: to conduct basic research on vaccines offering long-lasting, protective immunity, to prepare vaccine candidates, and to do laboratory analysis, animal testing and, ultimately, clinical trials of candidate products.

Nabel said he hopes to attract industrial partners to the VRC, and mentioned three activities to occupy the VRC in coming months: survey scientific opportunities, formulate (with the help of the Food and Drug Administration) appropriate regulatory guidelines in the areas of pharmacology and toxicology, and foment the involvement of biotechnology and drug companies in VRC pursuits. "We would be delighted if an industrial partner did the GLP lab for us," he said.

Within the "scientific opportunities" rubric, Nabel mentioned three categories: immunology (developing methods to enhance the immunogenicity of specific HIV peptides, exploring the still mysterious area of adjuvants, attracting primate virologists and immunologists); translation (generating novel vectors for sustained expression and immunogenicity, and developing assays of immune function that are both robust and high-throughput, though he warned, "The consensus is that we don't want to become simply an assay lab.") and clinical investigation. "A major priority for the center would be to promote clinical investigation and evaluation of candidate vaccines in humans," Nabel emphasized. "Clearly, a number of vaccine candidates are ready for human trials."

Given that there are five major HIV strains in the world, Nabel said he "would be very surprised if the ultimate composition of an HIV vaccine is monovalent."

Another retreat theme was "complementary NIH intramural programs," a feature that Nabel said "will make the VRC much more than it can be on its own." Intramural science deputy Gottesman reviewed existing vaccine programs on campus, the Intramural AIDS Targeted Antiviral Program, the NCI-Frederick program in vaccine development, the proximity of FDA's Center for Biologics Evaluation and Research on campus, plus a variety of resources such as NIAMS' Protein Expression Laboratory.

"About 100 (NIH intramural) principal investigators work on AIDS-related projects," Nabel said. "Ten percent of the intramural budget is now spent on AIDS-related studies."

Nabel suggested creating an HIV Vaccine Special Interest Group on campus, and concluded his remarks urging attendees at the workshop to apply for VRC positions.

He was followed on the program by a scientist who made all too clear the urgency of the VRC's mission. Dr. Jose Esparza of the Geneva office of UNAIDS reported that, 18 years into the AIDS epidemic, more than 40 million people are infected, more than 12 million are already dead, and that some 90 percent of new cases are arising in developing countries. "Sixteen-thousand people are infected with HIV every day," he said.

Nabel assured a questioner that "our perspective is global...clearly it is a global pandemic."


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