Could the Smallpox Vaccine Protect Against HIV?

A study published in the open-access journal BMC Immunology suggests an intriguing hypothesis: The explosion of spread of HIV in Africa and then worldwide in the 1950s might be partially explained by the eradication of smallpox and the discontinuation of smallpox vaccination campaigns.

The researchers - Raymond S. Weinstein, Michael M. Weinstein, Kenneth Alibek, Michael I. Bukrinsky, and Brichacek Beda - tested this hypothesis by collecting peripheral blood mononuclear cells from 20 subjects, half of whom had not been vaccinated against smallpox and half of whom had received the smallpox vaccination between three and six months previously. They then compared the susceptibility of the cells to two different strains of HIV - CCR5-tropic HIV-1 and CXCR4-tropic HIV-1. Here's how they describe the results in their abstract:

Vaccinia immunization in the preceding 3-6 months resulted in an up to 5-fold reduction in CCR5-tropic but not in CXCR4-tropic HIV-1 replication in the cells from vaccinated subjects. The addition of autologous serum to the cell cultures resulted in enhanced R5 HIV-1 replication in the cells from unvaccinated, but not vaccinated subjects. There were no significant differences in the concentrations of MIP-1alpha, MIP-1beta and RANTES between the cell cultures derived from vaccinated and unvaccinated subjects when measured in culture medium on days 2 and 5 following R5 HIV-1 challenge.

Since "primary HIV-1 infections are caused almost exclusively by CCR5-tropic HIV-1 strains," they conclude that "prior immunization with vaccinia virus might play a role in providing an individual with some degree of protection to subsequent HIV infection and/or disease progression."

The provisional PDF of the article explains that the idea of smallpox vaccines protecting against HIV isn't based solely on the idea that HIV's explosion coincided with smallpox's eradication. Co-infection with other viruses (including those that cause human herpes, dengue fever, and measles) has been demonstrated to inhibit HIV-1, although the protective effect generally seems to disappear once the co-infecting virus is no longer detectable. Research also suggests that both HIV and pox viruses require the chemokine receptor CCR5, and pox virus infections could alter CCR5 expression in a way that interferes with HIV's activity.

This study shouldn't be interpreted to mean that we've got an AIDS vaccine, but it does point to a promising direction for new research. For decades, the scientific community has been trying to create an effective HIV vaccine, but multiple trials have ended with disappointing results. If an already existing vaccine can play a role in protecting against HIV infection or disease progression, it will represent an enormous breakthrough.

I also think it's great that this research was largely driven by a desire to find a better explanation for why a disease suddenly started spreading quickly. Hooray for scientific curiosity!

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The article says, "Beginning in the mid to late 1950s, both types of HIV entered a phase of
exponential spread, first within Africa and then around the world."

By Liz Borkowski (not verified) on 26 May 2010 #permalink

The authors by "Theorizing that this phenomenon may be somehow related to the eradication of smallpox followed by the cessation of vaccinia immunization" ignore the epidemiology of HIV. In the US, routine smallpox immunization continued until 1972, with close to universal coverage. If the theory were to hold water, highest attack rates in the US would have been in people born after 1972. Routine use of smallpox vaccine in the rest of the world continued until around 1980.

By David Sencer (not verified) on 26 May 2010 #permalink

The most recent (This Week in Virology) podcast had a very amusing converstation about this paper. In short: they were not impressed.

Oh, and they mentioned this blog as a "Pick of the Week."

Cool podcast - thanks for the link! (And I'm not just saying that because they linked to us ...) Is it just me, or does the main host sound like Ira Flatow of Science Friday?

For those who haven't heard the podcast, they described some previous work addressing HIV and CCR5, questioned the epidemiology (for instance, if smallpox vaccination ended in 1978, wouldn't the cases we were seeing in the 80s have been children rather than middle-aged adults?), and put the size of the effect in context. It seems that the fivefold increase the researchers found is actually pretty modest - when testing a drug or vaccine, researchers look for at least a tenfold reduction. And one of the hosts commented, "I like to see things happen in logs."

By Liz Borkowski (not verified) on 28 May 2010 #permalink