Vaccine shown effective against chancroid

Could reduce HIV transmission: Study

CHAPEL HILL HIV plagues more than 25 million people in sub-Saharan Africa, according to the World Health Organization, and efforts to develop a vaccine against the virus have achieved limited success.

But what if a vaccine against another sexually transmitted infection found widely in that region of Africa chancroid was relatively easy to develop and could reduce transmission of HIV as much as 10-fold?

That may be the case, according to researchers from the University of North Carolina at Chapel Hill's School of Medicine and N.C. State University's College of Veterinary Medicine.

Their study appears in the April issue of the journal Infection and Immunity. The lead author is Dr. Galyna Afonina, postdoctoral research associate in the UNC Center for Infectious Diseases. Senior author is Dr. Christopher Elkins, research associate professor in the departments of medicine and microbiology and immunology in UNC's School of Medicine.

Chancroid, a sexually transmitted disease that causes genital ulcers, is rare in the United States but takes hold in communities that have little or no access to health care, such as in Africa. Recent studies show that genital ulcer diseases such as chancroid can enhance HIV transmission three- to 10-fold.

"There is considerable evidence that genital ulcers are independent risk factors for the transmission of HIV, and chancroid may be the most important one," said Elkins.

Chancroid is caused by a bacterium, Haemophilus ducreyi, that normally infects only humans. Unlike most bacteria, Haemophilus species are unable to synthesize heme, the ferrous, or iron-containing, component of hemoglobin, and obtain it from host hemoglobin.

The researchers found that immunizing swine with a purified hemoglobin receptor protected the animals from a challenge infection, even after multiple attempts at infection.

Blood tests showed that the immunized pigs formed antibodies that prevented the chancroid bacteria from binding hemoglobin and, hence, obtaining the heme it needs to survive, the authors said.

In skin biopsies of the immunized animals, the researchers found no viable chancroid bacteria.

An HIV vaccine has been elusive in part because the virus constantly varies its surface molecules, making it an ever-changing target. But H. ducreyi, unlike other sexually transmitted bacteria, doesn't have such a protective mechanism.

The current study and other studies suggest that developing a chancroid vaccine would be a relatively simple task, Elkins said.

Commercial sex workers infected with chancroid form a "reservoir" of infection, Elkins said. A vaccine strategy of vaccinating female sex workers against chancroid could shut down the cycle of infection, eliminating the disease of not only sex workers but their sexual partners.

And evidence suggests that eliminating chancroid throughout Africa could help reduce the transmission of HIV.

"Diverting but a fraction of the effort on HIV potentially could rapidly lead to a chancroid vaccine. I believe it is imperative that international and U.S. agencies address this opportunity in a timely manner," Elkins said.

In addition to Afonina and Elkins, other UNC authors are postdoctoral research associate Dr. Isabelle Leduc and postdoctoral trainee Dr. Igor V Nepliouev, both of the Center for Infectious Diseases; Dr. Marcia Hobbs, research associate professor in the departments of medicine and microbiology and immunology; and Chrystina Jeter, former undergraduate research assistant in Elkin's lab.

Authors from N.C. State University's College of Veterinary Medicine are Patty Routh, research technician; Dr. Glen Almond, professor of population health and pathobiology; and Dr. Paul E. Orndorff, professor of population health and pathobiology and microbiology and immunology. Elkins said that further development of the vaccine studied is needed, including perfecting ways to purify large amounts of the hemoglobin receptor substance and testing it with an adjuvant approved for human use.

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Funding for the research came from the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health.

School of Medicine contact: Leslie H. Lang, (919) 843-9687 or llang@med.unc.edu


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