Human immunodeficiency virus (HIV) is a quick-change artist, infamous for eluding all of the cells that the immune system can throw at it. That's why, in all the 20-odd years since that AIDS virus surfaced to bedevil humankind, no effective vaccine has arisen to prevent or put down HIV infection. Now researchers at the University of Alabama/Birmingham (UAB) announced that they have unmasked a novel mechanism by which HIV escapes the body's natural defenses. It's reported in Nature, dated March 20, 2003, under the terse title: "Antibody neutralization and escape by HIV-1."

Its senior author, microbiologist George Shaw, told BioWorld Today, "This paper may have important implications for vaccine studies. When a virus invades," he explained, "the body produces antibodies that target and destroy the pathogen by attaching to it and preventing it from entering and replicating within cells. Viruses generally escape those so-called neutralizing antibodies by changing their surface structure to preclude the antibodies from latching on. With most viruses, this change occurs at the specific sites on the pathogen's surface where the antibody would normally attach.

"However with HIV," Shaw continued, "researchers found that the virus avoids antibody recognition in a fundamentally different way. HIV changes its mutated gp160 coat protein at multiple locations distant from those antibody-combining sites. Escape results from steric - pre-atomic position - repulsion of antibody binding by an ever-shifting cloud, or shield, of sugar molecules called glycans, which coat its surface. We coined the term evolving glycan shield,'" Shaw vouchsafed, "to describe this novel mechanism of viral evasion.

"Our first step in unmasking the interaction between virus and HIV antibodies," he went on, "was development of a new blood test to confirm the presence and activity of HIV-neutralizing antibodies. The second was to analyze changes in the genetic composition of HIV in a patient's blood over the course of his or her illness. By combining this new lab test for viral resistance to antibodies with genetic and biological changes in a patient, we confirmed the presence of viral inhibition and escape from neutralizing antibodies.

"Surprisingly," Shaw observed, "the part of the protein usually recognized by antibodies - the so-called epitope - does not change. Rather the sugar molecules that decorate the envelope protein alter, seemingly shielding off the protein from recognition by the neutralizing antibodies. An ever-evolving sugar shield may thus help HIV-1 to escape the human immune system."

The test developed by the UAB team showed that HIV antibodies are effectively eliminating more sensitive strains of virus. "Unfortunately," Shaw noted, "as the antibodies are working to rid the body of one viral strain, new and more resistant strains are emerging. In infected individuals, the body's defense system is continually playing catch-up. By the time the immune system launches a counterattack by making neutralizing antibodies, there is already a massive amount of HIV in the body. It's been estimated that as many as 10 billion HIV virions are generated daily - leading to infection of many millions of cells long before neutralizing antibodies are first detectable.

"In humans not yet infected," Shaw speculated, "a vaccine designed to induce the production of neutralizing antibodies might turn the table on HIV, giving the body's defense mechanism the upper hand, or perhaps preventing infection altogether. In the presence of pre-existing neutralizing antibodies, the AIDS virus might not be able to escape."

The new test, or others like it, might prove useful in evaluating HIV antibody-inducing vaccines already being developed and tested. "Meanwhile," Shaw pointed out, "scientists can be satisfied in knowing that they have added one more piece to the complex HIV/AIDS puzzle."

Snorting Corticosteroid Inhaled Powder Is New Option For Treating Mild Asthma

Results of a large international study, reported in the current Lancet, dated March 29, 2003, provide strong evidence that inhaled steroids could substantially reduce illness associated with mild asthma. The paper is titled: "Early intervention with budesonide in mild persistent asthma: A randomized, double-blind trial." Its authors are a consortium of pediatricians at seven centers in Europe, China, Singapore, Canada and the U.S.

Previous research, the authors noted, has not established whether steroids could be effective in controlling mild asthma, mainly because people with moderate disease symptoms were included in earlier studies. The consortium conducted a randomized clinical trial in more than 7,200 patients 5 to 66 years of age from 32 countries to assess the effects of budesonide (Pulmicort Turbuhaler, AstraZeneca plc). Onset of the disorder has to be recent (within two years) and patients had not received previous treatment with steroids. They were randomly allocated to be given either inhaled budesonide or placebo once daily for three years in addition to their usual asthma medication."

Of the cohort that received the steroid, 44 percent developed severe asthma attacks (emergency visits and hospitalization), compared with placebo controls. They were 40 percent less likely to require systemic corticosteroids and had more symptom-free days than the controls. While budesonide improved long-term function and was well tolerated, it did have a negative influence on growth for children less than 11 years of age. Their three-year growth was reduced by 1.34 centimeters (half an inch) compared with children given placebo.

"Our study has shown," the principal author commented, "that once-daily low-dose budesonide decreases the risk of severe exacerbations and the need for systemic steroids in patients with mild persistent asthma and that the drug improves their overall control of the respiratory disorder. The benefits of this treatment outweigh the small effect on growth in children. Our results provide new evidence for recommendation in treatment guidelines about the use of inhaled steroids as early intervention in mild persistent asthma."