Smallpox vaccine may confer immunity to HIV

Cross-immunity between disparate viruses

Could smallpox — the historic scourge of mankind and still the most feared of the bioterror agents — be a major weapon against the global HIV epidemic? Might fire be fought with fire? As provocative as that sounds, a bioterrorism researcher is building a case that smallpox historically may have blocked the emergence of HIV and vaccinia may now provide the basis for a vaccine against the AIDS virus.

An epidemiological review of the emergence of HIV-1 in Sub-Saharan Africa and the eradication of smallpox in the same region suggests a correlation between the two, implying the possibility of a cross-immunity between these widely disparate viruses, says Raymond S. Weinstein, MD, a researcher at the National Center for Biodefense at George Mason University in Manassas, VA.1

As smallpox was eliminated as a natural disease and human immunity waned, HIV was no longer held in check and began to emerge and infect the human population, he theorizes.

Studies that have looked a the emergence of HIV-1 and HIV-2 support the theory. Both variations of HIV probably first appeared around 1940 (plus or minus 20 years), he notes.

"What are the chances of two different viruses emerging in two different locations within the same decade that are derived from viruses that have been around for thousands of millennia?" he asks Bioterrorism Watch. "It’s an awfully big coincidence. However, if you [postulate] that smallpox was suppressing the emergence of HIV — which actually did exist in extremely low numbers — then you can see that stopping the [smallpox] immunizations and loss of immunity to smallpox is what allowed HIV to spread."

Weinstein has tested the hypothesize in one study involving 20 volunteers and now is attempting to replicate the results in a larger group of 60 test subjects. The researcher and colleagues are testing the susceptibility to HIV-1 infection in peripheral blood mononuclear cells (PBMCs) from subjects recently immunized with the vaccinia virus.

"The hardest part is finding the subjects and getting them together to get fresh blood because it doesn’t work with frozen blood," he says. "We found that [PBMC] cells from individuals that were vaccinated within the previous three to nine months were resistant to infection with HIV. We don’t know yet what the mechanism is, but it may be that in patients who haven’t been infected it may prevent infection. Or some patients may get infected, but [smallpox vaccination] prevents progression [of HIV]."

Results demonstrate that immunization resulted in a fourfold reduction in viral replication with macrophage- (CCR5) tropic HIV-1, but not with T-cell- (CXCR4) tropic virus. This reduction in R5-HIV replication was further enhanced when autologous serum was added to the cell cultures. Since the vast majority of new HIV-1 infections are with an R5 tropic strain, these findings suggest that vaccinia immunization might be a new useful tool in the fight against the worldwide HIV pandemic, Weinstein emphasizes.

In particular, evolutionary pressure from naturally occurring smallpox disease appears to have spurred the development of a genetic mutation called CCR5 Delta 32, he explains.

"People who have that mutation are resistant to HIV. They are not just long-term survivors, but people who have multiple exposures and never become infected. It was the constant pressure from smallpox that [prompted] the success of that [mutation] It started as a single mutation somewhere between 800 and 1200 years ago in Northern Europe," Weinstein says.

"Now, one out of 10 people has it. It protected them against smallpox, but now that there is no smallpox, we are finding that it protects them against HIV, too," he adds.

If the findings are borne out in subsequent peer-reviewed studies, the possibility exists for an HIV vaccine or treatment based on the vaccina virus (cowpox) vaccine commonly used for smallpox. Also, the researchers are looking at the possibility of eventually using — as yet unapproved — smallpox vaccines that use nonreplicating vaccina for immunization of immunocompromised people.


  1. Weinstein RS, Alibek K, Weinstein MM, et al. Protection against HIV-1 infection in vitro by prior immunization with vaccinia virus. Plenary address abstract. Presented at the First International Conference — Crossing Boundaries: Medical Biodefense and Civilian Medicine. Arlington, VA; November 2003.