The Bay Area Reporter - December 22, 1995
William Snow, ACT UP/Golden Gate Writers Pool

Public and community support for developing an AIDS vaccine has been limited by lack of understanding of what vaccines are, how they work, and the unique issues of developing a vaccine against HIV. So here are some vaccine basics, along with current opinions about HIV vaccines.

The immune system is our defense system for recognizing and eliminating a variety of foreign invaders. When functioning properly, your immune system can tell the difference between foreign molecules and the body's own cells and proteins. In many cases it can marshal an immune response to eliminate or neutralize the invader. When you get sick, some of your symptoms, such as fevers, rashes, etc., are actually your immune system's attack on the invader. Frequently, when it is over, you are then protected against that invader.

In fact, the discipline of immunology grew out of this observation that individuals who had recovered from certain infectious diseases were protected from ever getting the disease again. In ancient Greece, it was known that only those who had recovered from the plague could nurse the sick because they would not contract the disease a second time.

With AIDS there is no proven instance of the immune system protecting an individual from infection or disease. But there are intriguing examples - multiply-exposed individuals who remain negative and long-term non-progressors - that suggest at least partial natural protection may rarely occur. Many basic scientists are trying to identify what the reasons or "correlates" for protection could be.

It took almost 2000 years for the concept of immunity to be used for a medically effective vaccination. At the beginning of the 19th century Edward Jenner was intrigued that milkmaids who contracted a mild disease called cowpox were afterwards immune to smallpox, a disfiguring and often fatal disease. He reasoned it might be possible to protect people from smallpox by inoculating them with fluid from a cowpox sore. He tested his idea by inoculating an eight-year-old boy with fluid from a cowpox pustule; later he intentionally infected the child with smallpox. The child was protected, though the experiment was certainly not safe or ethical.

(A similar circumstance exists in parts Africa, where HIV-1 and HIV-2 are both circulating. Recent research indicates that infection with HIV-2, a much less pathogenic virus than HIV-1, may protect some individuals from HIV-1 infection later.)

Jenner's technique spread quickly through Europe, but it was almost a hundred years later before it was applied to other diseases, by Louis Pasteur - by accident. Pasteur returned from vacation and injected some chickens with cholera that had been fatal before his vacation; to his surprise, the chickens recovered. Aging had weakened the cholera bacteria, which could then be used to protect against disease; this is called an "attenuated" strain. Pasteur extended his findings to other diseases. Although Pasteur proved that vaccination worked, he didn't understand the mechanisms involved. He developed his vaccines empirically, that is, by trial and error. Even today, some scientists believe that the best way to develop an AIDS vaccine is to put resources into working out the mechanisms of protection, while others believe in the empirical approach.

Long-term consequences

Vaccines in use today follow only a few basic designs. Most common are live attenuated vaccines like the two discussed; these are composed of a live virus or other pathogenic organism that has been altered to reduce or eliminate its potential to produce disease. Also common are inactivated virus vaccines which use virus that has been killed, or rendered unable to replicate.

Vaccine companies have been reluctant to pursue these traditional approaches of vaccine design for HIV because of the risk that some small amount of HIV in a killed vaccine may not be adequately killed, which happened with early Salk polio vaccine, or that attenuated HIV could revert to a pathogenic strain or have long-term consequences we wouldn't know about for many years. But there are proponents pushing for each of these approaches.

Aside from these traditional vaccines, which are made from the disease causing organism, new "subunit" vaccines are composed of only part of the pathogen. One of these, against hepatitis B, is prepared by recombinant bio-technology (genetic engineering). Most candidate AIDS vaccines to date have been of this type.

Vaccines have been developed for many other diseases that were once major afflictions of mankind. The incidence of diseases such as diphtheria, measles, mumps, whooping cough (pertussis), German measles (rubella), polio, and tetanus have declined dramatically as vaccination has become more common. Presently vaccines are in development for HIV, CMV, malaria, and other diseases.

Vaccination is a cost-effective weapon for disease prevention, which is amply and dramatically demonstrated by the total eradication of smallpox. There has not been a single naturally acquired case of smallpox since 1977 anywhere in the world. Despite this progress, more than 5 million infants worldwide continue to die each year from diseases that could be avoided by existing vaccines.

And, for economic or scientific reasons, vaccines are nonexistent or not readily available for several serious diseases. For example, more than 250 million people are chronically infected with hepatitis B virus, for which there is a relatively new and expensive vaccine. Malaria causes 1-2 million deaths per year (no vaccine yet, but possibly a partially effective candidate vaccine is in field trials). And despite unprecedented efforts, no effective vaccine has yet been developed against HIV, which has infected tens of millions of people.

It is also useful to remember that the number of infectious agents for which we have so far failed to develop a satisfactory vaccine is much greater than the number where we have been successful.

Cellular/humoral

We have learned much about immunology since the early days, one of the more important aspects of which is that there are two basic kinds of immunity: humoral or antibody immunity, which neutralizes infectious agents in the liquid (non cellular) part of the blood; and cellular or cell-mediated immunity, which kills infected cells.

Since it's possible to become infected with HIV as free virus, which antibodies could detect, or with infected cells, which are only susceptible to cellular immunity, many scientists believe both kinds of immunity will be needed for an AIDS vaccine that would prevent infection.

Another important element is the route of infection. Injection drug users are infected directly into their bloodstream. Sexual transmission is through mucosal surfaces, which have their own immune system, which we know very little about.

Recent advances in immunology have led to the development of new and promising vaccine strategies, and many of these are being tried to develop AIDS vaccines. While some are calling for a return to the traditional methods of vaccine development, which have greater risk but also perhaps greater chance of success, others are pushing for newer high-tech approaches because of the unique nature of this disease and challenge. In both cases it will take determination and a series of vaccines and human trials to develop products that will have impact on the epidemic.

Future articles will look at social, ethical, and political issues for vaccine trials, possible adverse reactions to HIV vaccines and other risks involved, funding, and the status of vaccines as therapy.
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Always watch for outdated information. This article first appeared in 1995. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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