By David N. Leff

Editor's note: Science Scan is a roundup of recently published, biotechnology-relevant research.

In the planet's underdeveloped countries - the "Third World" - the main killer diseases are malaria, tuberculosis and AIDS. But a close runner-up is measles, with 1 million deaths annually in the 1990s. One-third of its victims are children. In advanced nations of the First World, measles is well on its way to eradication.

In the four decades since introduction of an attenuated live-virus vaccine in 1962 stopped the virulent measles scourge in its tracks, cases of the infection in the U.S. have dropped from half a million a year to around a thousand. However, there's a siding on that trackage.

In infants under the age of 9 months, the otherwise highly efficient vaccine runs up against the immaturity of their immune systems, which are still relying on their mothers' antibodies for protection against infection. But those very maternal antibodies interfere with antibodies generated by the vaccine. That's why more than one-third of all measles fatalities occur to babies in their first year of life.

There's more to this horror story:

In the early 1990s, along came a novel vaccine - 100 to 1,000 times more potent than the 1962 model - that inactivated its virus with formaldehyde. This vaccine, designed for use in the Third World, proved immunogenic in recipients as young as 4 months to 6 months of age. However, it led to a severe reaction in 15 percent to 60 percent of vaccinated children. They developed a strangely severe form of the infection called "atypical" measles, with fatal side effects such as diarrhea, pneumonia and parasitic diseases. For no known reason, it increased deaths among girl babies in particular. These mysterious ravages put an effective brake on attempts to develop a more effective vaccine to protect 1st-year infants.

At last, DNA and recombinant technology came riding to the rescue. Virologist Diane Griffin rose to that occasion.

She chairs the department of microbiology and immunology at Johns Hopkins University School of Hygiene and Public Health in Baltimore. Griffin is senior author of an article in the July issue of Nature Medicine. Its title sums up her strategy: "Successful DNA immunization against measles: Neutralizing antibody against either the hemagglutinin or fusion glycoprotein protects rhesus macaques without evidence of atypical measles."

The single-stranded RNA measles virus consists of six proteins. Two of them, the viral envelope's hemagglutinin [H] and fusion [F] glycoproteins, manage the cell fusion by which the virions break and enter their target host cells in the human victim's respiratory tract. Aside from its other presumed advantages, their paper pointed out, "the ability of DNA to directly transfect cells could bypass interference from maternal antibody."

Instead of attempting once again to attenuate the live virus, Griffin and her co-authors constructed a DNA vaccine armed with immune-system molecules aimed at just those two recombinant viral glycoproteins, H and F. By definition, their synthetic plasmids couldn't replicate or infect. But they could trigger mammalian immune responses.

As human stand-ins to test their vaccine, the co-authors immunized 14 juvenile rhesus macaque monkeys. On these surrogate primates, they tried out different combinations of H and F, administered by three different delivery routes - subcutaneous, intradermal and biolistic (DNA gene gun).

A single dose of DNA vaccine, whether loaded against H or F or both, elicited neutralizing antibodies in all 14 macaques. Eight of the 14 (57 percent) developed protective antibody levels. After a booster shot 17 months later, antibody titers rose by 300 percent to 1,500 percent.

Besides these in vitro responses, the monkeys also were shielded against infective challenge by wild-type measles virus. Gene gun inoculation was 100 percent effective, and 62 percent of monkeys vaccinated intradermally also gained protection from infection.

In an editorial accompanying Griffin's article, pediatric infectious disease specialist Ann Arvin, at Stanford University, concluded: "Although they hold much promise, DNA vaccines will rival the available live attenuated vaccines only when inoculation procedures are simplified and theoretical advantages for enhancing immunogenicity in early infancy are translated into practice."

Culturing Pancreatic Duct Tissue In Vitro Yields Scarce Insulin-Secreting Islets For Transplantation

It's taken decades of research to develop ways and means of culturing and transplanting insulin-secreting islets of Langerhans into insulin-deficient patients with diabetes. About 35,000 new cases of diabetes Type I are diagnosed annually in the U.S. alone. Now that the technique is proving viable, the irony is that not enough islets are available. (See BioWorld Today, June 14, 2000, p. 1.)

Efforts to culture them in vitro have been hindered by their limited growth potential. Now a new source of islets is reported in the current Proceedings of the National Academy of Sciences (PNAS), dated July 5, 2000. The paper's title: "In vitro cultivation of human islets from expanded [pancreatic] ductal tissue." Its authors, at Harvard Medical School in Boston, report success in growing islet cells from a "bed" of expanded human ductal tissue "fertilized" with a coating of a natural complex of proteins and polysaccharides. In three to four weeks of culture, the authors observed a 10- to 15-fold increase in insulin content, and formation of structures they call "cultivated human islet buds." What's more, these buds secreted insulin in response to glucose.

Bacteria Engineered To Emit Luminescence Permit Imaging Antibiotic Action In Live Animals

A collaboration between research pediatricians at Stanford University Medical Center and scientists at Xenogen Corp., in Alameda, Calif., has produced an illuminating technology for discovery of new drugs to treat infections caused by Gram-positive bacteria. The authors report this development in the June issue of the journal Infection and Immunity, under the title: "Monitoring bioluminescent Staphylococcus aureus infections in living mice using a novel luxABCDE construct."

Imaging the high levels of light emitted by these bacteria, the company points out, the efficacy of new drugs against bacterial infections can be assessed non-invasively in real time in living animals. As their paper reports, S. aureus strains engineered to luminesce were injected into mice, then treated with an antibiotic. At eight hours, the infection had begun to clear, as evidenced by a decrease in light emission. At 24 hours, no light signal could be detected.