By David N. Leff

Whether or not oral sex constitutes sexual intercourse, it is definitely not safe sex - if one partner harbors the AIDS virus.

A variant form of oral sex - parturition - infects newborn babies with HIV at the very moment they emerge from the birth canal into the outside world. "The idea would be," explained immunologist Ralph Steinman at Rockefeller University in New York, "that the child, during birth, swallows infected fluid from its HIV-positive mother, and then is infected through the oral lymphoid tissue of the mouth or intestine. I think," he added, "that parturition is the critical time for viral transmission.

"What that's saying," Steinman pointed out, "is that you want to treat the woman right away, at the time of delivery, which is now being recognized as maybe the essential time, rather than in utero - though people debate about that." Breast feeding too, he observed, can transmit the infection orally.

A research report in the current Science, dated Aug. 20, 1999, of which Steinman is an initiating co-author, describes the in vivo experiment underpinning this rationale. Its title: "Rapid infection of oral mucosal-associated lymphoid tissue with simian immunodeficiency virus [SIV]."

"That title," Steinman told BioWorld Today, "is the main message, that what is called mucosal-associated lymphoid tissue [MALT] is very permissive for the transmission of an immunodeficiency virus. In this case," he went on, "it happens to be in an oral lymphoid tissue, so it may pertain to transmission of these viruses during parturition and oral sex." Steinman heads the Laboratory for Cellular Physiology and Immunology at The Rockefeller.

He and his collaborators at the German Primate Center in Gvttingen inoculated groups of rhesus monkeys with SIV, delivered not by needle but by cotton swab, soaked in a virus solution. They dabbed these very gently on to the tonsils of the animals, taking care to avoid breaking the delicate mucosal surface. Such a trauma might have shunted the pathogen from its intended lymphatic immune pathway to the blood, with its B and T white cells, and their immune defenses.

Tonsillar Target A Must

"The key thing," Steinman said, "was to actually put the viruses directly on the tonsil tissue. There had been some recent evidence that you could - just by putting the virus in the mouth - bang, get viral transmission. But that way you couldn't tell where the infection was. One of the easy conclusions had it just going through the lining of the throat, which has some similarities to the lining of the vagina, the anus and the ectocervix." (See BioWorld Today, May 10, 1999, p.1; and June 7, 1996, p. 1.)

On the third day following the tonsillar inoculation, there were few infected cells, but between days 4 and 7 the viral count had reached a high plateau. Moreover, no viral infection could be detected on the dendritic-cell-loaded squamous epithelium to which they had applied the virus. Instead, it was primarily in CD4+ tonsillar T cells.

"In fact, what we saw," Steinman recounted, "was that not only was the lymphoid tissue a very permissive transmission site, but that the external lining-type areas that are similar to the throat lining and the vaginal lining, in fact weren't infected at all, that we could see." Dendritic cells (DCs) present - i.e., introduce - foreign antigens to the immune system's antibody-producing B cells and foreign-cell-killing T cells.

"That was one of the secondary findings," Steinman said, "that these surface-type epithelia, where there are dendritic cells, didn't seem to be actively participating in the transmission. It was mainly the mucosal tissue. It was the strategy of putting the virus directly on the tonsil area that really opened things up, I think.

"DCs tend to be localized where antigens enter the body," Steinman explained, "and one such place is the skin and the linings of the female genital tract and the anus. But there, they are not sitting right at the surface, but deeper down. So in order for DCs to have access to the antigen, there may need to be something else. It could be trauma, inflammation. Maybe, for example," he speculated, "there's evidence that hormonal changes thin the lining of the female genital tract. Again, that could even change the DCs to make them more accessible. In the steady state, these tissues really aren't accessible to the DCs."

Vaccinologists: Make Room For MALT

His research aims at securing for mucosal tissue targets a seat at the table where AIDS vaccines are developed. "What we point out," Steinman continued, "is that the rate at which the virus multiplies in this tissue is extraordinarily fast. That means if you're going to have a vaccine, the immune mechanism has to be in place very quickly. And it may have to be present locally at the mucosal site, which is one of the challenges in current HIV vaccines that isn't emphasized. We just don't have good vaccines that block viral infections transmitted through mucosal surfaces.

"So, how do you design a vaccine," Steinman asked rhetorically, "that's most effective, meaning, first of all, efficacy - a strong immune response - and second, getting that response localized to viral point-of-entry body surfaces. We may have to focus more directly on these MALTs. They may be a very good route through which to vaccinate someone preventatively.

"What we're now setting up to do," Steinman allowed, "is capitalize on this route to vaccinate. These are just our own experiments that we're just starting. I'd rather not highlight them. And the other thing we're doing is trying to get the vaccine directly to the dendritic cells, your body's natural pathway for initiating T-cell-type immunity. We would generate the DCs ex vivo, apply the vaccine, then put them back into the individual."

He made the point, "The important thing is to establish the principle that we can or cannot get very strong immunity if we target the DC, trying to mobilize all the things we know it does. If we knew that, then maybe vaccinologists would start paying a little more direct attention to this physiologic pathway - because they're not. The fact is that most vaccines are just designed to be given willy-nilly without DCs consciously in mind.

"I think we're just calling attention to the fact - it's not news - that you have these special mucosal organs that are designed to pick up antigens. I think we need to target these organs as directly as we can, to elicit strong immunity. Let's take advantage of this pathway," Steinman concluded, "not be victimized by it."