Experts Examine Global Progress in Vaccines Against a Variety of Deadly Infectious Agents

ARLINGTON, Va. -- Many of the world's leading vaccine scientists are meeting this week at the National Foundation for Infectious Diseases' (NFID) sixth annual Conference on Vaccine Research to present the latest research on vaccines against familiar diseases such as E. coli, measles, rotavirus and smallpox. Other research being reported will address vaccines against malaria, influenza and HIV and those in veterinary practice, how the immune system responds to vaccines, and changing patterns of vaccine discovery, production and use worldwide.

"The last several years have witnessed profound changes in the vaccine enterprise that have been driven, in part, by philanthropy, geopolitics, and scientific advances," says David A. Neumann, PhD and associate director of the NFID. "The information presented at the conference reflects the breadth and depth of current vaccine research, and sets the stage for enhancing public health globally."

The sixth annual Conference on Vaccine Research is a noncommercial scientific forum that brings together specialists from diverse disciplines such as microbiology, immunology, genetics, epidemiology, and public health. Following are summaries of several studies being presented at the sixth annual Conference on Vaccine Research:

New Vaccine Against Enterotoxigenic E. coli (ETEC) Tested

Although Escherichia coli (E. coli) bacteria are typically found in the human intestinal tract, enterotoxigenic strains are a common cause of pediatric diarrhea throughout the developing world, and can cause diarrhea among adult travelers to such areas. Most cases of ETEC-caused diarrhea result from ingestion of inadequately washed or prepared foods. Worldwide, the bacteria cause an estimated 400 million episodes of diarrhea in children under the age of five annually, which results in 700 thousand deaths.

Capt. Stephen J. Savarino, MD, of the Naval Medical Research Center in Silver Spring, Md. and an international team has tested a new oral vaccine against ETEC disease in infants and toddlers in Egypt. In the recently completed randomized, double blind efficacy trial, Savarino's team observed 31 episodes of non-severe ETEC-associated diarrhea among the 152 children given the vaccine and 40 episodes among the 162 children given a control preparation. This difference was not statistically significant, but several of the lessons learned can be effectively applied to speed up ETEC vaccine development. Overall, the results suggest that a killed ETEC vaccine is feasible, but that giving greater doses may be necessary to achieve protection.

Study Evaluates a DNA Vaccine Against the Measles Virus

Measles, which is relatively uncommon in the United States, continues to cause high rates of morbidity and mortality in other parts of the world. Breast-fed children may not be protected when given the current vaccine, because they receive anti-measles antibodies from their mothers that neutralize the virus in the vaccine, preventing the children from developing their own protective immunity.

Mary F. Premenko-Lanier of the University of California at Davis and colleagues at the Centers for Disease Control and Prevention (CDC) and the Harvard Medical School has developed a unique approach to this problem. In their study, a plasmid containing the gene encoding IL-2 was administered 48-hours after immunization, to act as an adjuvant. Two groups of animals were used, with one receiving anti-measles immunoglobulin prior to immunization to mimic the presence of maternal (passive) antibodies.

"The IL-2 gene was effective in enhancing the immune response to the DNA vaccine, significantly reducing peak levels of viremia relative to levels observed in animals not given the adjuvant," reported Premenko-Lanier. This finding suggests that DNA vaccines may be effective in eliciting immunity even in the presence of maternal antibodies, potentially offering a new tool to public health practitioners working toward the global elimination of measles disease.

Study Demonstrates Potential of a Candidate Rotavirus Vaccine

In severe rotavirus cases, diarrhea can lead to dehydration, electrolyte imbalance and other life threatening complications, primarily in children. This is a particular problem in developing countries where medical and other resources available to treat rotavirus-infected children are lacking. Given the continuing, substantial burden of rotavirus-caused disease, there is considerable interest in developing a safe and effective vaccine against this virus.

Richard L. Ward, PhD, of the Children's Hospital Medical Center in Cincinnati, Ohio and his colleagues are developing a new rotavirus vaccine known as VP6 that is showing great promise in early evaluations. Mice from five strains were given two intranasal or two oral doses of two different formulations of VP6 and adjuvant. Four weeks later they were challenged by oral exposure to mouse rotavirus.

In all five strains of mice, virus shedding was reduced by 99% among those given the mouse-derived form of VP6 relative to that observed among control animals. Shedding was reduced by 86% among those given VP6 derived from a human rotavirus. In one mouse strain, both intranasal and oral immunization with either form of VP6 resulted in similar levels of protection. Ward noted, "Mucosal immunization with VP6 and an effective adjuvant consistently protected mice against rotavirus shedding, which indicates that further evaluation of this candidate vaccine is warranted."

Progress in the Development of the Next Generation Smallpox Vaccine

The smallpox vaccine that is currently being used to vaccinate members of the public health and health care communities and personnel of the Department of Defense is known to cause various adverse reactions. With the possibility of more widespread use of the vaccine looming, there is considerable interest in developing a new, safer vaccine. Richard N. Greenberg, MD, of the University of Kentucky College of Medicine, Lexington, Ky. and colleagues are evaluating reactions to a newly formulated smallpox vaccine.

"The new vaccine, known as CCSV, contains a strain of the vaccinia virus that is grown in cell culture," said Greenberg. The DryVax vaccine that is currently being used contains a similar virus and was produced by infecting cows. The new study compares skin rashes among adult volunteers administered either CCSV or DryVax.

Greenberg said, "We observed post-vaccination rashes in two of 100 DryVax recipients (2 percent) and in six of 250 CCSV recipients (2.4 percent)." The rashes appeared six to 19 days after vaccination, resolved within three to 22 days, and responded to treatment with antihistamines. The rashes varied in appearance from hundreds of small spots to larger lesions, and the location of the lesions was also variable.

"Because of the small number of volunteers in this study (350), it was not possible to determine the true incidence of rash for either CCSV or DryVax," said Greenberg.

The vaccine conference is jointly sponsored by eleven prestigious organizations: the National Foundation for Infectious Diseases, the Centers for Disease Control and Prevention, the Center for Biologics Evaluation and Research of the Food and Drug Administration, the Center for Vaccine Development at the University of Maryland, the International Society for Vaccines, the International Vaccine Institute, the Merieux Foundation, the National Institute of Allergy and Infectious Diseases, the Netherlands Vaccine Institute, the Sabin Vaccine Institute, and the United States Department of Agriculture.

The conference is funded, in part, through unrestricted educational grants from Antigenics, Inc.; Aventis Pasteur; Baxter Healthcare; Becton, Dickinson and Company; Bioject, Inc.; Chiron Corporation; Coley Pharmaceutical Group; Dynport Vaccine Company; GlaxoSmithKline; Iomai Corporation; MedImmune; Merck Vaccine Division; Powderject Vaccines, Inc.; U.S. Food and Drug Administration; VaxGen; Vical, Incorporated; and Wyeth Vaccines.

Source: National Foundation for Infectious Diseases

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