HIV/AIDS: Vaccination & Natural Resistance

Vaccination & Natural Resistance

HIV Vaccine: The Holy Grail of Containment

In the mid-1980s, United States Health and Human Services Secretary Margaret Heckler predicted a brief epidemic for AIDS and said, “there will be a vaccine in a very few years and a cure for AIDS before 1990.” Today, it is still recognized that the best hope for stopping the pandemic lies with a vaccine. Vaccines eradicated smallpox and contained polio, but the prospect for an AIDS vaccine is nowhere in sight.

How Can This Be?

One problem is that HIV protects itself by producing chemicals that block antibodies from killing it. However, the larger problem relates to the number of different strains of HIV. In reality, HIV is not a single virus, but a family of related virus subtypes called “clades.” The AIDS pandemic has been caused by eight clades, labeled A through H, of HIV-1. In addition, new strains are continuously being generated because HIV changes rapidly through mutation and genetic recombination, which mixes genetic information from virus subtypes to create new ones.

The eight HIV-1 subtypes are not evenly distributed around the world. Rather, they exist in distinct geographic clusters. For example, subtype B is most prevalent in Europe, North and South America, Japan, and Australia, while subtypes A, C, D, and E are spreading rapidly in Africa and Asia. This family diversity suggests that a single vaccine would be unlikely to cover all clades. In fact, some researchers lament that an effective vaccine for industrialized countries would not work against the HIV subtypes prevalent in the developing world.

Researchers generally agree that for a vaccine to be truly effective both humoral (antibody) and cell-mediated (B cells and killer T cells) arms of the immune system need to be activated. Antibodies can protect against initial infection, while B cells and killer T cells confer long-term immunity. Regrettably, our current vaccine candidates have been unable to induce both types of protection.

Yet the search continues with glimmers of hope. Researchers have made progress in prodding the body to track down and destroy HIV-infected cells for up to two years. Even if a vaccine fails to prevent infection, such medications could still limit the course of disease, keeping viral loads low, and reduce the risk of serious complications.

Natural Resistance to HIV Infection

Some people with HIV exposure don't progress to AIDS. In the mid to late 1990s, scientists noted that persons with one copy of a mutated gene were less likely to become infected with HIV, while individuals inheriting two copies of the mutated gene were highly resistant to HIV infection. The mutated gene, called CCR5-32, helps HIV invade T cells. The gene defect prevents the host cell from binding with the HIV. Unfortunately, the gene defect is rare, with about 1 percent of whites having two genes with the CCR5 mutation and even fewer nonwhites.