ALEXANDRIA, Va. -- Researchers at this week's Conference onAdvances in AIDS Vaccine Development are discussingstimulating mucosal immunity as a first-line of defense againstHIV.

The mucous membranes of a Homo sapiens could cover one anda half tennis courts, or 222 times as much ground as the skin,Jiri Mestecky of the University of Alabama, Birmingham, saidat the conference, which is being held here by the NationalInstitute of Allergy and Infectious Disease of the NationalInstitutes of Health.

"The absolute majority of infectious agents enter through themucosal surfaces," including HIV, said Mestecky. Butworldwide, these other agents cause far more morbidity andmortality than the AIDS virus. Together, diarrheal andrespiratory tract pathogens cause nearly a million cases perhour, compared with 340 cases for HIV. For mucous-protectingvaccines, then, the scope of opportunities is "tremendous,"Mestecky said.

Since AIDS is most commonly spread through unprotected sex,stimulating mucosal immunity could provide a first-linedefense. At the conference, one scientific session, one workshopand more than several individual talks addressed this subject.

"The mucosal and systemic immune compartments are largelyindependent," explained Mestecky. "The mucosal antibodies aremostly of local origin." But scientific understanding of thegenital mucosal immune system is poor, Mark Feinberg, aprofessor of medicine at the University of California, SanFrancisco, told those at the conference.

Mestecky has studied induction of immune response againstsexually transmitted diseases, generally in females. "There area number of antibody-forming cells in individual segments ofthe female genital tract, most common in the endocervix,followed by the fallopian tubes and the vagina," he said.

Key questions include: "What factors regulate levels ofantibodies and magnitude of immune response in the femalegenital tract? What is the origin of precursors of Ig-producingcells in the female tract? What type of intraepitheliallymphocytes are in the fallopian tubes?"

Feinberg and his colleagues have pursued polio viruses ascandidate vectors in the quest for mucosal immunity. Thevirus' big advantage, which Albert Sabin recognized in the1950s when he developed the oral polio vaccine, is that itreplicates in mucosal tissues, eliciting local immunity.

In preliminary studies, Feinberg has successfully inserted theintact HIV sequences, gag, env, and nef into attenuated poliovirus, Raul Andino, Feinberg's colleague in the microbiologyand immunology department, told BioWorld. So far, theresearchers have observed antibodies against gag in infectedmice.

The engineered virus maintained the ability to replicate, whichis necessary to elicit T cell immunity. But the researchers havenot yet looked for this immune response in mice yet.

In monkeys, Feinberg has found that virus shed in feces isgenetically stable, which suggests that it could be used tovaccinate those in developing countries without refrigeration, amajor consideration given the virus' epidemiology.

So-called M cells are the door between the outside world andinductive sites of the mucosal immune system, Andino toldBioWorld. Preventing M cell-mediated transport might be partof a first line of defense, but an HIV vaccine must also be takenup via M cells.

And in humans, the rectum contains the highest concentrationof these cells -- "highly significant for an HIV vaccine," saidMarian Neutra of the Department of Pediatrics at HarvardMedical School.

In her efforts to find ways to prevent M cell-mediatedtransport of pathogens across the sexually exposed mucosalsurfaces, Neutra found that only rectal immunization couldinduce large quantities of secretory IgA in mucous coating inboth the rectum and distal colon and in the cervix and vagina.Neutra used mice in her experiments. For test antigens, sheused cholera toxin and recombinant gp120.

Anti-gp120 secretory IgA antibodies may block M cell-mediated transport by preventing HIV or virus-infected cellsfrom contacting epithelial surfaces, according to Neutra.

-- David C. Holzman Washington Editor

(c) 1997 American Health Consultants. All rights reserved.