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Vol. LXIII, No. 9
April 29, 2011
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'A Light for the World'
Vaccine Research Center Celebrates First Decade

On the front page...

Dr. Gary Nabel
VRC director Dr. Gary Nabel has led the center for all of its history and credited its people as its main strength.

When NIH director Dr. Francis Collins called the Vaccine Research Center “not only a light for NIH and the United States, but also a light for the world” on the occasion of its 10th anniversary celebration Mar. 31 at Natcher Bldg., he could have been anticipating the breadth of the succeeding scientific symposium. The 4½-hour session ranged the globe as top experts in the field unpacked everything from the design of sophisticated new molecules built to block HIV infection, to new strategies for creating a universal flu vaccine, to evidence—harvested largely from many thousands of animal fecal samples from the wilds of Africa—of HIV’s primate origins.

Still, the birthday present all in attendance most keenly desired—an effective AIDS vaccine— remains an elusive goal.

Continued...

“I consider it the outstanding failure of modern biology,” said Nobel laureate and Cal Tech biology professor Dr. David Baltimore, in closing remarks, “that we have not yet delivered [a vaccine] when society is most in need.

“But that’s not for a lack of will, or of skill,” he continued, “but because of the inventiveness of nature, which is ahead of our technology.”

The VRC, Baltimore said, embodies the hopes of a scientific community “that has not yet given up…Let a thousand flowers bloom,” he said, before launching into a description of efforts in his own laboratory to “engineer immunity” to HIV by creating neutralizing antibodies that could be delivered by intramuscular injection.

According to VRC director Dr. Gary Nabel, the center’s first and only leader, the past 2 years have seen dramatic progress in structure-based design of candidate HIV vaccines. “I consider pre-2009 the Dark Ages,” he said.

Two antibodies (originally derived from a patient with HIV infection)—VRC 01 and VRC 02—have been developed to block HIV from entering human immune cells and appear to be effective against most strains of HIV. These antibodies, and others recently isolated, “open a new window on broadly neutralizing antibodies,” said Nabel. “I expect dozens, and perhaps hundreds, more as we converge on a common, shared epitope.”

Dr. Francis Collins Dr. Glenda Gray Dr. David Baltimore Dr. Beatrice Hahn

NIH director Dr. Francis Collins opened the anniversary, calling the VRC “an exciting and highly productive part of the NIH community.”

Photos: Michael Spencer

Dr. Glenda Gray of the University of Witwatersrand explained why a vaccine is so important to her country: “HIV is not in recession in South Africa.”



Nobel laureate Dr. David Baltimore, professor of biology at Cal Tech, said the VRC embodies science’s relentless search for an effective HIV vaccine.


Dr. Beatrice Hahn of the University of Alabama, Birmingham, has traced the origins of HIV-1 to Africa in the 1920s.




Right from the start, the VRC fashioned itself as a center for all of vaccinology, not just AIDS, explained two of the center’s founding influences, NIAID director Dr. Anthony Fauci and NCI director (and former NIH director) Dr. Harold Varmus. They made the case for a vaccine center to the Clinton administration in the mid-1990s.

The crucial meeting, said Fauci, took place Dec. 3, 1996, at the White House, when the NIH scientists briefed Clinton and Vice President Al Gore on HIV biology, capturing their attention. Five months later, at a commencement address at Morgan State University in Baltimore, Clinton announced plans for a new vaccine center on the NIH campus. Barely 2 years after that, Clinton presided over the laying of the cornerstone of the Dale and Betty Bumpers Vaccine Research Center, which opened in 2001.

While the bulk of the symposium focused on HIV, Nabel, Fauci and others underscored the VRC’s valuable contributions to vaccines for:

Influenza—A universal vaccine—based on a DNA prime and vector boost—has emerged as a possibility within the past 4 years. Ebola—A vaccine that proved effective in nonhuman primates is now in human trials.

SARS—Fauci said the virus was first characterized on Mar. 24, 2003, and that by Dec. 13, 2004, a SARS vaccine entered clinical trials. “That’s truly the world’s indoor record,” he quipped. “That is light speed.”

Epstein-Barr virus—Varmus emphasized the importance of an EBV vaccine to global health since it could prevent infectious mononucleosis and certain neoplastic diseases with which it is associated.

West Nile virus—The VRC is a major leader, Fauci said, in proof-of-concept studies of a DNA vaccine.

Chikungunya virus—The VRC has crafted a VLP (virus-like particle) vaccine that is entering phase I trials with Merck. Chikungunya, noted Fauci, is a serious disease in the developing world.

Said Nabel, “The complementarity of different vaccine approaches has been extremely helpful.”

Dr. Gary Nabel
NCI director Dr. Harold Varmus was among the first at NIH to recognize the importance of a physical and intellectual center for vaccine study on campus. He said the VRC sends an important signal about maintaining strong support for vaccine studies in an era that has become suspicious of the therapy.

Two of the day’s speakers made it clear that vaccinology these days cannot be practiced without a passport. Dr. Beatrice Hahn, professor of medicine and microbiology at the University of Alabama at Birmingham, collects fecal samples at sites throughout Africa to study viral pathogens and parasites. She gave evidence that HIV-1 originated around 1920 in chimpanzees and NIAID director Dr. Anthony Fauci gave the “30,000-foot overview” of VRC activities in the past decade.estimated that the virus spent 60-80 years in people without being recognized. “AIDS afflicted chimpanzees long before humans,” she said.

Dr. Glenda Gray of the University of Witwatersrand in South Africa underscored why the hunt for an HIV vaccine is so crucial. In her country of 49 million people, HIV prevalence is around 11 percent, or 5.6 million people. Thirty percent of the pregnant women in South Africa harbor HIV, she said, and life expectancy there is only 49 years.

“The fabric of society is incredibly damaged by the high rate of death in women at the peak of their child-bearing years,” she said.

Only one-third of the patients who need antiretroviral therapy in South Africa actually get it, she continued, and about 10 million men need circumcision, which can lower the transmission of HIV.

Given the challenge of outlining where the field moves next, Cal Tech’s Baltimore applauded the recent focus on antibodies. “That is the most important attitudinal change,” he said. He is encouraged by mouse studies in his lab whereby an adeno-associated virus acts as a delivery system for antibody production.

Concluded Nabel, “I hope that by the 15th reunion, we’ll be talking about the [HIV] vaccine.”

Meet the Combatants: HIV vs. VRC

NIAID director Dr. Anthony Fauci gave the “30,000-foot overview” of VRC activities in the past decade.
NIAID director Dr. Anthony Fauci gave the “30,000-foot overview” of VRC activities in the past decade.

The Vaccine Research Center is not just the gleaming tower on the west side of campus, colloquially known as Bldg. 40 (and a decent place to talk about science over pizza, noted NIAID director Dr. Anthony Fauci, who visits a few times each month for updates). There are three complementary components: NVITAL (NIAID Vaccine Immunogenicity T-Cell and Antibody Laboratory) in Gaithersburg, a small GMP (Good Manufacturing Practices) vaccine pilot plant in Frederick, Md., and a core clinical facility in the Clinical Research Center, not to mention the “Vaccines for Life” van that serves as a mobile HIV clinic.

The VRC has 211 employees, has published more than 670 papers, has created 37 products used in trials and has completed 41 clinical trials. Twelve trials are ongoing or planned for 2011. Nearly 5,000 research subjects have been enrolled in VRC trials over the last decade, for all diseases under its purview.

On the other side of the ring is HIV. At least 33 million people around the world are living with HIV, said Fauci. For the past 10-15 years, the number of new HIV infections in the U.S. alone has hovered stubbornly in the neighborhood of 56,000.

HIV has infected more than 60 million people since the first cases were reported almost 30 years ago, in June 1981, said VRC director Dr. Gary Nabel, and there have been more than 25 million deaths. Each year, about 1.8 million people die of AIDS, creating a situation where, with 2.6 million new infections each year, the number of people living with HIV continues to increase. NIHRecord Icon


Gallery

NIAID director Dr. Anthony Fauci lauded the VRC staff (shown in image behind him) as “some of the finest in the world.” He visits the facility once or twice a month for research updates, which he said leave him feeling “very exhilarated.”
Dr. Ashley Haase, head of the department of microbiology at the University of Minnesota Medical School, studies how to prevent HIV infection in women and has come up with at least two strategies that he presented Mar. 31 at the VRC 10th anniversary.
Dr. Beatrice Hahn of the University of Alabama, Birmingham, talks with Dr. David Baltimore (c), professor of biology at Cal Tech and VRC director Dr. Gary Nabel during a break in the symposium.
Dr. Margaret “Peggy” Johnston, who retired from NIAID last December and currently works as a consultant, meets with Dr. Jose Esparza, senior advisor on HIV vaccines for the Bill and Melinda Gates Foundation; he is also a member of the senior scientific advisory board for NIAID’s Center for HIV-AIDS Vaccine Immunology.
Dr. John Mascola, deputy director of the VRC, helps run a center whose sense of camaraderie was evident at the anniversary.
VRC director Dr. Gary Nabel has led the center for all of its first decade. “This is all about people,” he said, as the screen behind him showed top staff, “foremost, those we’re trying to help…the core team deserves all the credit.”
Dr. Ian Wilson of the Scripps Research Institute spoke about prospects for a universal influenza vaccine. “This is pretty exciting times for flu,” he said. “Structure-assisted vaccine design is now possible…the floodgates are now open.”

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