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The Race to End HIV: Two Paths Toward an HIV Vaccine

Research published today shows that early childhood vaccinations may be one way to teach the immune system the tricks HIV uses to evade it.

That’s because a recent vaccine trial that proved ineffective showed that the vaccine induced antibodies not only reacted with the HIV envelope, but also with common intestinal microbes. This same interplay has been observed in the setting of acute HIV infection, when the virus takes hold.

“We know that the intestinal microbiome can influence the types of antibodies that develop after birth when the microbiome is established,” said Dr. Barton F. Haynes, director of the Duke Human Vaccine Institute and senior author of the study appearing online today in Science Express. “Our study raises the hypothesis that the microbiome imprinted the immune system to make these cross-reactive antibodies. It suggested that one way to improve the antibody response may be to block the undesired HIV sites during vaccination, or to vaccinate earlier in life to imprint the immune system on desired HIV regions.”   

The Duke-led researchers wanted to see if the vaccine would mimic “the same diverted, ineffective antibody response that occurs with acute HIV infections,” Haynes said.

The vaccine basically kept the immune system very busy, but because the area of the HIV envelope targeted by the vaccine, gp41, had the same molecular makeup of some of the intestinal bacteria, the immune system’s resources were ineffective on the HIV cell envelope.

“The keys to inducing a successful HIV antibody response may be to mitigate or get around the virus’s ability to divert preexisting B cells that are cross-reactive with intestinal microbiota,” said lead author Wilton B. Williams, Ph.D. “We are currently exploring early vaccination strategies and exploring new designs of the HIV viral envelope to induce the correct antibodies.”

It hypothetically could mean that someday young children would get an HIV pre-vaccine along with DTaP before beginning kindergarten, for example.

“Because the microbiome serves as a training ground to teach the immune system how to fight pathogens, HIV’s ability to mimic common microbiota suggests that a successful HIV vaccine approach might also include early childhood immunizations,” the Duke news release explained. “This could provide a way to prime the immune system to better identify and attack HIV.”

HIV Vaccine Quest Likened to Putting Man on the Moon

Meanwhile, the raging debate continues over the two different approaches being undertaken to develop an HIV vaccine. The research coming out of Duke today is part of a “theoretical approach” that has been criticized as costly and with very little data to show for all of the money spent.

Proponents of the painstaking theoretical approach liken the quest for an HIV vaccine to the arduous process of putting man on the moon, and likewise a significant investment.

As part of a larger goal to create a vaccine with broadly neutralizing antibodies, or bNAbs, this sort of research already has cost the National Institute of Health about half a billion dollars in the past 10 years, according to a Healthline News story published last year.

“Concurrently, scientists pursuing a theoretical approach have made strides in characterizing powerful broadly neutralizing antibodies (bNAbs) that target many HIV strains and develop naturally over time in a minority of HIV-infected people,” NIAID reported Tuesday in a news release. “Scientists hope to design vaccine regimens that stimulate the immune systems of uninfected people to produce bNAbs. Recently, researchers have made progress toward this goal, for example, by developing a stable version of the HIV envelope trimer—the HIV surface protein that is a target of known bNAbs—that potentially could be used as an immune-stimulating vaccine component.”

Critics have said that less inexpensive, empirical approaches – trying unique approaches for different vaccinations, one idea at a time – may ultimately lead to a breakthrough. But some scientists have likened that approach to throwing things at a wall to see what sticks.

Proponents of such empirical approaches point to the modest success of the RV144 vaccine, which showed a 31 percent reduction in HIV acquisition.

“At the same time as bNAb-based research and other early stage approaches, such as T-cell-based vaccines, move from theory to design, research stemming from RV144 may improve on the modest efficacy seen in Thailand,” NIAID explained in the news release.

“Ultimately, the theoretical and empirical approaches will coalesce, converging upon the effective vaccine so critically needed to end HIV transmission worldwide,” the authors concluded in a commentary in Science.