VACCINE DEVELOPMENT AT NIH:

VRC RISES ON THE SHOULDERS OF GIANTS

Richard G. Wyatt

VACCINE RESEARCH IS . . . NOT A FIELD FOR THE FAINT OFHEART. BUT IT IS ALSO [ONE] WHOSE SUCCESS IS MEASURED IN ENORMOUS BENEFIT TO THE PUBLIC HEALTH. THERE ARE MANY EXAMPLES OF HIGHLY SUCCESSFUL VACCINES DEVELOPED IN NIH INTRAMURAL PROGRAMS AND DEPLOYED INTO THE WORLD . . . .

When, in a 1997 commencement address, the President called for creation of the Vaccine Research Center at NIH, he chose to place it in an institution with a rich history in vaccine development. Because NIH has its roots in the Public Health Service, development of vaccines and prevention of disease have been appropriately a part of our history nearly since NIH was founded in 1887.

In 1895, Joseph Kinyoun, the first head of the Hygienic Laboratory, NIH’s precursor organization, worked on diphtheria antitoxin that had just been developed in Europe. The Laboratory was later charged in 1902 with responsibility to test the purity of vaccines and antitoxins, because of concerns about contamination of biologicals.

These efforts remained a part of NIH until 1972, when they were transferred to the Food and Drug Administration. They remain an integral part of vaccine efforts today as a part of the FDA’s Center for Biologics Evaluation and Research on the NIH campus. These early activities of the PHS and its Hygienic Laboratory stimulated some of the first work in basic immunology because of anaphylactic reactions to biological products.

Later, intramural investigators, working at the NIH Rocky Mountain Laboratory (RML) in Montana, succeeded in preparing a chemically inactivated vaccine against Rocky Mountain spotted fever (RMSF) in 1925. This crude vaccine was made of ground-up, infected ticks and was used widely in Western states. Improvements followed when Herald Cox grew rickettsia at RML in eggs; this led to an improved RMSF vaccine and also to a typhus vaccine that was needed during WWII. Troops were also immunized during WWII with an improved yellow fever vaccine developed at RML in 1943 by Mason Hargett; the new versions avoided earlier problems associated with producing yellow fever vaccine with human serum. Further, the standardization of the initial cellular pertussis vaccine and of allergens was first achieved at the NIH Division of Biologics in the 1940s.

But we need not look only at the past to find legendary intramural investigators who have committed their scientific careers to the pursuit of vaccines. Now as then, persistence is a hallmark of NIH efforts that could well be compiled as a modern sequel to Microbe Hunters, Paul de Kruif’s 1926 classic that has, over the years, inspired more than a few students to develop vaccines for future generations.

Vaccine research is undeniably a high-risk endeavor—not a field for the faint of heart. But it is also an endeavor whose success is measured in enormous benefit to the public health. There are many examples of highly successful vaccines that have been developed in NIH intramural programs and deployed into the world: a live, attenuated adenovirus vaccine to combat respiratory disease in military recruits (1962), developed by Robert Chanock and Robert Huebner; Haemophilus influenzae type b vaccine (1988) and Vi vaccine for typhoid fever (1991), developed by Margaret Pittman, John Robbins, and Rachel Schneerson; an acellular pertussis toxoid (1998), prepared by Robbins and Ronald Sekura; hepatitis A vaccine (1985), developed by Robert Purcell and co-workers; and a tetravalent rotavirus vaccine (1998) development effort, led by Albert Kapikian.

Beyond these vaccines that have been brought to fruition are many others still moving through the pipeline: vaccines against respiratory syncytial virus, influenza virus, parainfluenza virus, hepatitis E virus, pneumococcus, group B streptococcus, meningococcus, shigella, and Escherichia coli O157, as well as a series of cancer vaccines under development in NCI, such as a papillomavirus vaccine.

During just the past decade, there have been approximately 200 invention reports submitted to NIH tech transfer offices on proposed vaccines developed by NIH intramural scientists. Several have already led to patents, and an astonishing 10 licenses have already been issued to companies that anticipate turning these NIH discoveries into commercial vaccines.

It is out of this rich legacy and churning activity that we now launch the Vaccine Research Center [see articles on VRC and Gary Nabel]. With the VRC’s infusion of direction and synergy, the future holds the exciting prospect of new focus and discovery that will lead to safe and effective vaccines against HIV/AIDS. We can be optimistic, based on historical precedent, that the desired HIV/AIDS vaccines will indeed emerge if investigators persist and remain committed to the field.

The tradition and commitment of secure, long-term funding and support from NIH leadership, in turn, will help to undergird our researchers’ determination as we strive to maintain the creative, stable, and inspirational milieu from which the work to create safe and effective vaccines against HIV/AIDS—and tuberculosis, malaria, and other major pathogens—can be pursued to success.

–Richard G. Wyatt

Executive Director, OIR

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