Preventing Infection: Vaccine protects against malaria in early test

An experimental vaccine against malaria has tested well in early research. The Anopheles mosquito, shown here, spreads the parasite causing malaria.

The long, bumpy path to a malaria vaccine may have hit a smooth stretch as an early-stage study finds that multiple injections with inactivated malaria parasites can protect against the disease.

The findings are tantalizing but preliminary. The study was small, and the vaccine required five intravenously delivered doses to work, which would be an obstacle for teams attempting mass vaccination in developing countries. Also, the shots were tested in adults, not children, who are the prime victims of malaria.

Still, the study offers decidedly good news, says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., which sponsored the research. “This is an important advance,” he says, noting that the vaccine induces an immune onslaught that kills the malaria parasite in its infective sporozoite stage. That means uninfected mosquitoes that bite a vaccinated person wouldn’t get infected, slowing the disease’s spread, he says.

In the study, researchers gave four or five shots to 15 volunteers over several months. The volunteers were then bitten repeatedly by malarial mosquitoes. A few weeks afterward, 12 showed no disease, including all six who got five doses, the researchers report August 8 in Science. A control group of unvaccinated volunteers got the disease and received treatment promptly.

Scientists already knew that weakened versions of malaria sporozoites could induce immunity in people. To turn the sporozoites into a vaccine, scientists need to irradiate infected mosquitoes, and use the weakened parasites to elicit an immune response in people. In the new study, scientists mastered the delicate task of attenuating the parasites just enough so that they don’t replicate and cause disease, but leaving them active enough to trigger an immune response that would kill any full-strength sporozoites introduced by subsequent mosquito bites. The researchers also effectively delivered the vaccine into volunteers — albeit with IV injections. In earlier tests, this vaccine failed to gin up adequate immunity when given by shots into the skin, which are easier to deliver.

“This is the first step towards success with this approach,” says Denise Doolan, a molecular immunologist at the Queensland Institute of Medical Research in Herston, Australia. “It has taken enormous dedication and perseverance to achieve this result, and [the researchers] should be congratulated.”

Study coauthor Robert Seder, a physician and immunologist at NIAID, says the research team plans to test the vaccine in more people and find out how long the protection lasts. A field trial is planned in Tanzania.

Doolan says simpler and fewer shots are needed for far-reaching vaccination campaigns. If such a vaccine can be developed, she says, it should “have a dramatic impact on public health.”

Meanwhile, Seder says, the IV vaccine — if fully tested and approved — might be useful for protecting health officials, military forces and travelers. Fauci cautions that while this vaccine showed effectiveness against one strain of Plasmodium falciparum, the parasite that causes the most severe kind of malaria, the vaccine will have to prove itself against other strains.

Decoding Cancer:HeLa genome offers clues to cells’ cancerous nature

A detailed DNA profile of the world’s most widely used cancer cell line sheds light on the genetic chaos the cells use to grow virtually unchecked in laboratory cultures. That property may also explain their virulent growth in the woman who unwittingly left them to science.

The famous cells came from a biopsy taken in 1951, when Henrietta Lacks was dying from cervical cancer at Johns Hopkins Hospital. Although no one asked Lacks or her family for permission to perform experiments with the cells, they formed the first immortal human cell line ever successfully grown in the lab. HeLa cells were pivotal in developing a vaccine for polio, among other scientific milestones.

But one problem for researchers using HeLa cells has been that their genome is a scrambled version of a normal human genome. This makes it more difficult to design and interpret experiments using the cells.

The new work, reported by University of Washington researchers in the Aug. 8 Nature, will help scientists make better use of HeLa cells by providing information on the arrangement of genetic variants on chromosomes.

These details were “long overdue,” says Peter Park, a computational biologist at Harvard Medical School. “We no longer have to make assumptions about what the HeLa genome looks like.”

Human cells normally have two copies of each chromosome. Sometimes, a genetic variant differs between the two copies. But standard sequencing methods mix the data together, so it’s impossible to figure out which variant is on which chromosome. The University of Washington group overcame that obstacle by using a method that identifies which variants sit together on the same chromosome.

This new level of detail helps reconstruct an event that is thought to have contributed to Lacks’ cells becoming cancerous. Scientists already knew that the HeLa genome contained human papillomavirus DNA, which comes from the genome-invading virus that causes nearly all cervical cancers. The virus DNA had embedded itself near MYC, a human gene that, when artificially switched on, can cause cells to become cancerous.

The new study found that in chromosomes with viral DNA, the MYC gene turned on. But in matching chromosomes without viral DNA, MYC was not active. That meant that the viral DNA probably turns the MYC gene on, but only within the same chromosome. The researchers also found that the viral DNA actually touched the MYC gene, suggesting it directly causes the different MYC activity on the chromosomes. This reveals one of the ways that the invading virus might have helped Lacks’ cancer cells to grow uncontrollably.

“It’s a really lovely piece of work,” says geneticist Daniel MacArthur of Massachusetts General Hospital. “It's a shame that the technical achievements of the authors may be overshadowed by the ethical challenges.”

The HeLa genome sequence was published for the first time in March, by a research group led by Lars Steinmetz at the European Molecular Biology Laboratory in Heidelberg, Germany. These data, published in G3: Genes, Genomes, Genetics, mapped out the many rearrangements and mutations that distinguish the HeLa genome from a healthy human genome.

The study sparked a controversy because the sequence was freely available and could potentially be used to infer some of the genetic variants carried by Lacks’ family. In response the team withdrew the HeLa sequences from the public database.

The National Institutes of Health has now negotiated an agreement with the Lacks family that restricts access to HeLa genome and requires future publications based on the data to acknowledge the contribution of Henrietta Lacks and her family. The new arrangement also has members of the Lacks family joining a board that oversees requests to use the data.