Can bacteria that cause food poisoning deliver oral DNA vaccines?
Shigella flexneri, one of many microorganisms that cause food poisoning, is an unpleasant bug. Fond of invading cells that line the intestines of humans, the bacterium causes gastrointestinal illness marked by diarrhea, stomach cramps, and fever that can last for a week or more. This type of Shigella is also one of the most infectious bugs around: An encounter with as few as 10 of these bacteria is usually enough to infect a person.
Nevertheless, Jerald C. Sadoff envisions a future in which adults and children, particularly those in developing countries, swallow a pill containing S. flexneri to ward off infectious diseases ranging from tuberculosis to AIDS. Sadoff, a bacteriologist now at Merck Research Laboratories in West Point, Pa., isn't crazy. He's merely one of many researchers pushing the envelope of a radical new form of immunization called DNA vaccines.
A number of investigators have recently proclaimed DNA vaccines the third revolution in vaccinology. The first, which celebrates its 200th anniversary this year, occurred when Edward Jenner demonstrated that inoculations with the cowpox virus protect humans from the ravages of smallpox. For decades, immunologists followed Jenner's lead, creating vaccines based either on microorganisms that infect other species or on weakened versions of the ones that cause disease in humans.
The second vaccine revolution took place recently, as the tools of molecular biology enabled researchers to identify and isolate specific antigens-usually proteins or protein fragments-from viruses, bacteria, and other infectious agents. Injections of some of these antigens have generated immune responses to the organisms from which they are derived. The vaccine for hepatitis B, for example, uses a protein found on the surface of that virus.
Over the last few years, in the face of initial skepticism, many research groups have shown that DNA vaccines are a potential alternative to the two traditional forms of vaccines. By simply injecting genes that encode antigens, investigators have stimulated immune responses to the antigens. Cells apparently process the foreign DNA easily, synthesizing the encoded antigens and igniting immunological retaliation against them. The immune responses may be more protective than those obtained by injecting the antigen directly (SN: 1/1/94, p. 6; 6/3/95, p. 343).
Vaccines based on this approach, often called naked DNA vaccines, have taken the first small steps into human trials against AIDS and cancer (SN: 2/17/96, p. 100).
DNA vaccines have gone "from a really unacceptable form of immunization a couple of years ago to something so promising now," marvels Harriet L. Robinson of the University of Massachusetts Medical Center in Worcester.
The science of DNA vaccines is still in its infancy, however. While most researchers resort to injecting DNA directly with a syringe or using so-called gene guns to shoot DNA-covered gold pellets through the skin, a few investigators, such as Sadoff, have explored the possibility of delivering future DNA vaccines orally.
Oral vaccines are desirable for a number of reasons, including cost and simplicity. Eliminating the expense of needles and of the professionals who provide the injections is a major advantage, especially when it comes to vaccinating millions of people in developing countries. "Oral delivery is ultimately easier," says Sadoff.
Oral vaccines may also provide a different, and more effective, form of protection than many injected vaccines. Injected vaccines place antigens directly in the bloodstream, which becomes the site of most of the protective antibody and cellular immune response. The bloodstream, however, may not be the best place to generate an immune response against certain microbes. Before they ever reach the bloodstream, many infectious agents must cross an often ignored part of the immune system known as the mucosal barrier. …