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Scientists eye new developments on the vaccine front

The vast range of pathogens and their ability to mutate beyond the reach of many antibiotics continue to challenge researchers.

By Susan J. Landers, AMNews staff. May 26, 2003.

Washington -- Vaccines that target influenza, measles, polio and pneumonia are wiping out those infections that have long taken a toll on human life. But there are plenty of other pathogens to keep microbe hunters on the job developing new vaccines to eradicate infections that are fatal to many patients, especially the youngest, oldest and most frail.

Microbiologists, epidemiologists and public health physicians gathered early this month for updates on the ongoing search for new vaccines at the 6th Annual Conference on Vaccine Research in Arlington, Va. The conference was sponsored by the National Foundation for Infectious Diseases.

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Presentations ranged from the search for a safer, next-generation smallpox vaccine to those that prevent infection by such nasty bugs as Staphylococcus aureus and Clostridium difficile.

The threat of bioterrorist attack has kept the smallpox virus center stage, prompting researchers to step up work on a new vaccine that can be used safely to inoculate individuals not currently deemed eligible for the existing one.

For instance, individuals who have a compromised immune system or a history of eczema are cautioned against receiving the smallpox vaccine unless there is an actual smallpox outbreak.

A new smallpox vaccine is being evaluated, said Richard N. Greenberg, MD, professor of medicine at the University of Kentucky College of Medicine in Lexington, although, because of the small numbers of volunteers in the trial, there is no definitive outcome.

"The new vaccine, known as CCSV, contains a strain of the vaccinia virus that is grown in cell culture," Dr. Greenberg said. DryVax, the vaccine now in use to immunize those deemed first responders to bioterrorist attacks, contains a similar virus but was produced by infecting cows.

Vaccines that target the following infectious agents also were described as being in varying stages of development, although none has gained Food and Drug Administration approval for general use.

Staphylococcus aureus. A phase III clinical trial has shown that the vaccine StaphVAX is providing some immunity against S. aureus infections among a group of trial participants who were undergoing hemodialysis. The new vaccine targets a sugar molecule on S. aureus that allows the pathogen to evade the body's immune system. Findings from the trial were published last year in the New England Journal of Medicine.

Another vaccine, Veronate, has completed a phase I trial.

Providing urgency to the development of an effective vaccine is the increase in antibiotic-resistant strains of S. aureus and their emergence as a source of community-acquired infection.

This constantly growing resistance to existing antimicrobials is troubling. The bacteria have been resistant to penicillin since the 1940s, and strains resistant to methicillin have been noted since the 1960s. Resistance to vancomycin, the so-called last resort antibiotic, surfaced in 2002.

Pseudomonas. A vaccine to target Pseudomonas aeruginosa has been sought for years. It would be particularly important for children with cystic fibrosis. By 15, nearly 100% of children with the chronic disease harbor large numbers of the bacteria that cause pulmonary infections. Phase I trials have now concluded for the vaccine candidate Cytovaxine.

Respiratory syncytial virus. In the United States, it is estimated that 70,000 to 126,000 infants are hospitalized annually with RSV pneumonia or bronchiolitis. RSV can also cause life-threatening pulmonary disease in bone marrow transplant recipients, and it is a major source of infection for elderly people. Two types of candidate vaccines are in clinical trials.

Clostridium difficile. Vaccines are also in development for C. difficile, a major cause of diarrhea among hospitalized elderly and immunocompromised patients. The pathogen is also responsible for most cases of antibiotic-related diarrhea.

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