Smallpox vaccine and HIV Link?

by Gilbert Keith

Smallpox demise link to HIV boom

The worldwide eradication of smallpox may, inadvertently, have helped spread HIV infection, scientists believe.

Experts say the vaccine used to wipe out smallpox offered some protection against the Aids virus and, now it is no longer used, HIV has flourished.

The US investigators said trials indicated the smallpox jab interferes with how well HIV multiplies.

But they say in the journal BMC Immunology it is too early to recommend smallpox vaccine for fighting HIV.

I just looked at this article in BBC News. I’m a little confused by the science mentioned in the article. A later paragraph states:

The researchers believe vaccination may offer some protection against HIV by producing long-term alterations in the immune system, possibly including the expression of a receptor called CCR5 on the surface of white blood cells, which is exploited by the smallpox virus and HIV.

I figured that I’d learn more by actually reading the paper, and it turns out it was a pretty good idea. A “provisional PDF” of the paper is available here.

The authors drew upon the idea that if a cell is already infected with certain viruses, progression of HIV-1 infection into the cell may be significantly slowed. Human Herpesvirus 6 and 7 and the dengue fever virus are some such examples. The CCR5 chemokine receptor (or its ligands) and the CD4 co-receptor. What’s so special about these receptors?

Well, interestingly, HIV-1 (a particular strain of HIV) uses the CD4 receptor to gain entry into T-cells. Binding to the CD4 receptor allows the virus to bind to the CCR5 or CXCR4 co-receptor (depending on the cell expressing the co-receptor), allowing the virus to fuse with the host cell. It is also known that individuals who have a 32 base-pair deletion in the gene coding for CCR5 do not produce the receptor and are resistant to infection by HIV.

The scientists hypothesized that “immunization [with the smallpox vaccinia vaccine] might confer some protection against initial HIV infection and possibly even disease progression.” The subjects for this experiment included 20 individuals, all of whom had received the same set of vaccinations and none of whom were HIV-positive. Furthermore, none of them had been immunized for smallpox. To 10 of the individuals, they gave the smallpox vaccine, while the other 10 were in the control group. About 6 months later, they collected blood samples from the subjects and centrifuged the samples to obtain the Peripheral Blood Mononuclear Cells (PBMCs) so that they could grow cultures of the cells. They then got two different strains of HIV and mixed them with the culture media or the serum from the subjects. The solutions were then inoculated into cell cultures.

They measured the level of viral replication and levels of certain chemokines in culture. The results showed that in the cultures treated with the R5 strain, the levels of viral replication increased exponentially over a 13-day period in the unvaccinated, but increased initially and plateaued in the the vaccinated samples. There was nearly a 4-fold decrease in the replication levels among the vaccinated samples compared to the unvaccinated samples. Similar results were observed both samples treated with serum and those treated without serum. For the cultures treated with the X4 strain, there was a rise in replication activity until day 5, but subsequently decreased; however, the difference in replication levels in the vaccinated and unvaccinated samples was not statistically significant. No significant difference was observed in the samples pre-treated with serum compared to those that weren’t.

The results also suggest that there wasn’t a difference between the replication levels 3 months after treatment and 6 months after treatment. This contrasts with the previous observations of resistance to co-infection. Infection with the dengue fever virus or the GBV-C only inhibits HIV infection so long as the virus is present; once the virus is cleared, HIV replication increases dramatically. An independent study over a longer timeframe gave nearly identical results. The authors also showed that the long-term expression of certain cytokines was also slightly increased in the vaccinated individuals, though the difference was not statistically significant.

Thus, the authors suggest that there might be an interaction between the HIV-1 strain and the vaccinia virus, and vaccination for the virus might confer resistance to HIV infection. Since the decline of the use of smallpox vaccine and the emergence of the HIV-1 pandemic have sort of coincided, there might be a link between the two events.

Cool stuff, no?

–Gautam

EDIT: I should clarify, I have basically summarized the paper. I haven’t bothered to cite all the stuff since the citations are the original paper. The link to the original paper is provided.

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