Oct. 21 (Bloomberg) -- Each of the Ebola vaccines being lined up for testing carries potential downsides, researchers say, ranging from efficacy that faded in less than a year to the chance it will give healthy people flu-like symptoms. In a worst-case scenario, they could do more harm than good.

Human trials, just starting on some vaccines, could also unveil unknown side effects, an unwelcome possibility for shots designed to be taken by people who may never be infected with Ebola. That’s why it’s imperative to cast a wide net in seeking a solution, said Matthias Schnell, a microbiologist at Thomas Jefferson University in Philadelphia.

“We really should test as many vaccines as we can,” Schnell, who is working on a vaccine that targets Ebola and rabies, said in a telephone interview. “We need way more clinical data for each vaccine before we go ahead with mass vaccination.”

© Steve Parsons/WPA/Getty Images Dr. Felicity Hartnell, who is a clinical research fellow at Oxford University, injects the vile of the ebola vaccine called Chimp Adenovirus type 3 (ChAd3) to Ruth Atkins, who is the first healthy UK volunteer to receive…

Because they are given to healthy people, vaccines have the potential to do more harm than good if serious unexpected effects occur, said Ben Neuman, a virologist at the University of Reading in the U.K. In 2007, for example, Merck & Co. halted trials of once-promising AIDS vaccine after a study found that people who got the vaccine may have been more likely to contract HIV than those who got a placebo shot.

In Ebola, a vaccine that creates an immune response that isn’t precisely targeted to shut down the virus might make it easier for the virus to infect healthy cells, Neuman said.

Clinical Trials

Safety testing has already begun on vaccines from GlaxoSmithKline Plc, which is working with the U.S. National Institutes of Health, and NewLink Genetics Corp., which is testing a product developed by government researchers in Canada. The next step, efficacy trials in humans, could start next year for Glaxo’s product in affected regions in Africa.

Meanwhile, clinical trials could begin later next year for as many as three other vaccines. While the vaccines have shown some levels of effectiveness in animals, that’s no guarantee they’ll work as well when they are tested in humans, said Thomas Geisbert, a virologist at the University of Texas Medical Branch in Galveston, Texas.

“That’s why it’s good to have an arsenal,” Geisbert said by telephone. “So that if one doesn’t work, you will have plenty of alternatives.”

Vaccines work by stimulating the body to generate antibodies with the ability to remember the virus. That allows them to recognize Ebola once an infection takes place, and mount a rapid counterattack. They differ from ZMapp and other experimental medicines given to Ebola patients primarily because the vaccines are designed for healthy people as a way to keep them from becoming infected.

‘Nasty Surprises’

The Glaxo and NewLink vaccines “have both been shown to be effective in monkeys, so there’s every reason to think they’ll be effective,” said Kartik Chandran, a microbiologist at the Albert Einstein College of Medicine in New York. “But you can’t assume the same thing will hold true in humans. There have been nasty surprises before.”

The vaccines from Glaxo and NewLink are based on modified viruses that are changed so they express an Ebola protein that’s strong enough to stimulate an immune response, but doesn’t carry the part of the Ebola virus that makes people sick. Glaxo’s vaccine is based on a chimpanzee cold virus, while the NewLink vaccine is based on vesicular stomatitis virus, which is found in cows.

For London-based Glaxo’s vaccine, there are unanswered questions about whether it will be able to protect against Ebola for an extended length of time, Schnell said.

Monkey Study

A study in monkeys, published last month in the journal Nature Medicine, showed efficacy of the single-dose version of the vaccine waning over several months. While one dose of the vaccine protected all of the monkeys given the vaccine from a lethal dose of Ebola after five weeks, it only protects about half of the animals after 10 months.

Giving the monkeys a booster shot of a different vaccine construct provided longer-lasting protection, but Glaxo isn’t using that version in its initial studies in humans.

Even with the one-dose version “we are hoping this vaccine will effectively prime the immune system so that when it does see a small amount of virus” the body will be able to mount an effective response, said Ripley Ballou, a Glaxo vice president.

Johnson & Johnson, meanwhile, plans to test a vaccine it developed with a planned booster shot. The company’s human trial is set to begin in March 2015. While giving everyone two shots rather than one adds a logistical challenge, J&J thinks it could be the best way to provide long-term protection.

‘Complete Protection’

It “has the potential to provide the durability needed to ensure complete protection against the disease, particularly when we don’t how long an Ebola outbreak will continue,” said Seema Kumar, a J&J spokeswoman.

Durability, though, remains a key question for Ebola vaccines, according to Geisbert. In Africa, if patients have to keep coming in for booster shots, “it could be a very big problem,” he said. “You are lucky to get someone to come in one time, not multiple times.”

Vaccines based on weakened, live viruses that can still replicate “tend to have more durability,” said Geisbert. But they may also cause flu-like symptoms in some cases, he said.

“If you get high fever after you get vaccinated, that would be the end of the vaccine,” Schnell said.

NewLink Vaccine

NewLink’s vaccine is one with a weakened live virus that can still replicate. The Ames, Iowa-based company has started trials in the U.S. and will soon start at other sites in Germany, Switzerland, Gabon, and Kenya, said Marie-Paule Kieny, the World Health Organization’s assistant director-general for health systems and innovation.

Healthy volunteers in the trial will receive the vaccine, and then be tracked to see how their body responds, NewLink’s Chief Executive Officer Charles Link said in an Oct. 14 interview. The first participants will get a very low dose of the vaccine to make sure it is safe before the dosage is gradually escalated for later subjects, Link said by telephone.

“We’re doing everything in our power to get the vaccine moving forward and get it into the hot zone,” he said. NewLink’s Chief Financial Officer John Henneman declined to comment on potential side effects.

For its Ebola vaccine, Profectus BioSciences Inc. has done extensive engineering on the cow virus used as a backbone to minimize any risk of side effects, said John Eldridge, chief scientific officer of the Baltimore-based company. Yet because it just received government funding to produce quantities of the vaccine needed for trials, human testing won’t begin until next June or July, he said.

While researchers often look at how well vaccines do in stimulating the production of antibodies, that isn’t always the best predictor, said Neuman, the virologist. For example, he said, vaccines for HIV have triggered a good antibody response yet failed in human testing.

“Ebola is good at hiding,” Neuman said in a telephone interview. Making a vaccine “is hard,” he added. “If it was easy we would have one by now.”