May 2010

On Monday, May 17, staff from the History of Vaccines project traveled to Washington, D.C. to attend “New Promise in the Search for HIV, TB and Malaria Vaccines,” a joint briefing held on the 30th anniversary of the eradication of smallpox.

In their opening remarks, Dr. Alan Bernstein (Global HIV Vaccine Enterprise), Dr. R. Gordon Douglas, Jr. (Aeras Global TB Vaccine Foundation) and Colonel Chris Ockenhouse (U.S. Military Malaria Vaccine Program, Walter Reed Army Institute of Research) all stressed the need for continued efforts toward vaccines for malaria, HIV, and TB. They also highlighted the overlap between the incidence of the three diseases, as well as the interaction between them: Douglas specifically stressed the importance of developing a TB vaccine that can be used in HIV-positive individuals.

We at the History of Vaccines project were happy to provide material for the keynote talk by Dr. Gregory Poland (Vaccine Research Group, Mayo Clinic). Dr. Poland discussed historical and contemporary challenges in vaccine development and deployment, including political agendas and the threat of diseases as bioweapons post-eradication. More

At the University of Pennsylvania School of Medicine on May 14, Arthur L. Caplan, PhD, Emmanuel and Robert Hart Director of the Center for Bioethics and the Sydney D. Caplan Professor of Bioethics at the University of Pennsylvania, gave a talk entitled “Ethical Lessons of Swine Vaccine Rationing.” Caplan, a widely quoted voice in bioethics, noted that the 2009 H1N1 pandemic provided testing ground for pandemic and even bioterror response planning. What can we learn from the experience?

Caplan described several areas for improvement. First, he noted the plethora of plans, developed at different levels of authority, for dealing with the pandemic. Hospitals, corporations, cities, and states developed plans with different priorities and rationales, some of them potentially at odds. Caplan highlighted the conflict between, for example, a state that might decide to quarantine itself to attempt to reduce importation of disease and a vaccine manufacturer in that state with a need to distribute its product. Would the state plan necessarily take the manufacturer’s needs into account? More

Most people view chickenpox as a disease of childhood–or, as the vaccine against it is increasingly used, as a disease of the past. But varicella zoster, the herpes virus that causes chickenpox, is sneaky. Even after a varicella infection clears, the virus hides in the nerve cells, inactive. In about 20% of people who have had chickenpox, the virus will reappear later in life to cause shingles, a disease of severe pain and blisters on the body or face. Blisters on the face can cause problems with vision and hearing, while the spread of the disease to the body’s internal organs can cause serious damage, including encephalitis (inflammation in the brain).

A vaccine against shingles was approved by the U.S. Food and Drug Administration in 2006 after it was shown to be effective (in clinical trials, the vaccine reduced the risk of shingles by 50%). Recently, a long-term follow-up study of 38,000 participants from the trial that led to its approval also demonstrated its long-term safety. (The study, from the Annals of Internal Medicine, can be found here.)

The use of the vaccine, however, does not reflect the data on its safety or effectiveness: a separate study, also in the Annals of Internal Medicine, indicated that despite the vaccine being available since 2006 and recommended since 2008 by the Advisory Committee on Immunization Practices for all adults 60 or older, early use of the vaccine has been between only 2% and 7% in the United States. (That study can be found here.) More

The United States Food and Drug Administration (FDA) recently approved Dendreon Corporation’s “cancer vaccine,” Provenge, for the treatment of certain types of prostate cancer. It became the first cancer vaccine to be approved for use in the United States. (Gardasil, Merck’s HPV vaccine, is sometimes referred to as an anti-cancer vaccine since it prevents infection with strains of HPV that cause cervical cancer. Dendreon’s product, however, is designed to directly treat cancer.)

Provenge is not a vaccine in the same way we would think about vaccines against measles, polio, or other infectious diseases. Those vaccines are designed to prevent infection by priming the immune system against a particular pathogen: a strain of a virus is weakened or inactivated, for example, and a mass-produced vaccine is created that can be administered for future protection against that virus before it can take hold in the body.

Provenge, however, is designed to treat existing cases of advanced prostate cancer, not prevent cancer. It works in a similar way to what we think of as a typical vaccine: by priming a person’s immune system to attack the disease. Attacking cancer is complicated, however, since cancer cells are actually the body’s own cells, making it difficult to “teach” a person’s immune system to identify them. Provenge is designed to stimulate a T-cell response to prostate cancer cells that are present. More

In the not-so-distant past, smallpox was a scourge of mankind. It spread wildly through vulnerable populations, killing up to 30% of those it infected; those who survived were left scarred, some seriously disfigured or blind.

Smallpox ravaged the world’s population essentially unchecked for more than 3,000 years, sickening Egyptian pharaohs, British royalty, American presidents, and millions in between. But in the 1970s, the disease was nearing the end of its reign. Thanks to massive vaccination and surveillance efforts, smallpox became the first disease to be eradicated from the world. Today, we celebrate 30 years since the people of the world declared themselves free of its grasp.

The last stand

The final case of naturally occurring smallpox took place in Somalia in October of 1977, in a cook named Ali Maow Maalin. Personnel from the global eradication program immediately began efforts to find every individual Maalin had been in contact with, doing house-by-house searches and vaccinating anyone entering or leaving his town. By December 29, 1977, they completed a national search, and Maalin’s case proved to be the last. He survived. More

In the United States, the Advisory Committee on Immunization Practices (ACIP) issues written recommendations regarding scheduling and dosing of vaccinations for both children and adults. ACIP members are selected by the Secretary of the Department of Health and Human Services to provide advice on controlling vaccine-preventable diseases; the committee is the only federal unit to make these recommendations.

ACIP issues new and updated recommendations when the status of a given disease changes, or when new data suggests that a vaccine dosage or schedule should be changed. Recently, in response to rabies surveillance data, clinical studies, experimental work and other factors, the Committee issued new recommendations for prophylactic rabies vaccination after possible exposure to the virus.

Rabies is nearly always fatal after symptoms begin to appear. However, if an exposed individual is treated promptly (with proper wound care and the administration of rabies immune globulin and rabies vaccine), the disease can usually be prevented. The previous ACIP recommendations were for five doses of rabies vaccine following exposure; now, the ACIP has reduced the dosage schedule, recommending only four doses of the vaccine for exposed individuals without prior protection against the disease. The details of ACIP’s updated recommendations are available as part of the March 19, 2010 Morbidity and Mortality Weekly Report. More

Although Escherichia coli (E. coli) commonly colonizes the human digestive tract and most of its infections are benign, some strains of the bacteria can be quite dangerous. A major subgroup of E. coli, called “extraintestinal pathogenic E. coli” (ExPEC) includes strains that are responsible for more than 80% of urinary tract infections, and are the second-leading cause of neonatal meningitis and sepsis cases (blood poisoning). Urinary tract infections are associated with high health care costs, and sepsis with high infant mortality rates; in addition, the ExPEC strains have shown increasing resistance to antibiotics. In light of these issues, the development of an effective vaccine has become an important priority in combating ExPEC strains.

Now, researchers have used “reverse vaccinology” techniques to identify specific proteins in a particular ExPEC strain–proteins that could possibly provoke an immune response and be used to create a vaccine.

A reverse vaccinology approach consists of examining a pathogen’s genome to find genes with attributes that could make good targets for vaccines. The researchers in this E. coli study examined the genome sequence of ExPEC IHE3034, an E. coli strain isolated from a case of neonatal meningitis. More