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Scientists Make Progress Toward a Safe, Effective Zika Vaccine

A biologist releases genetically modified Aedes Egypti mosquitoes in Piracicaba, Brazil, in February 2016. The modified mosquitoes, which cannot transmit Zika, compete with wild mosquitoes. Image Credit: Victor Moriyama/Getty Images

 
Zika virus has spread to almost 60 countries since early 2016. Almost 5000 cases have been identified in the United States, including more than 200 infections transmitted in Florida and Texas. Though the virus often causes only mild symptoms (or may not cause any symptoms at all), the link between Zika infection, microcephaly, and other developmental abnormalities has been strengthened with additional studies over the past year. However, a vaccine is still unavailable.

New research led by investigators at the University of Pennsylvania may move us closer to the goal of a safe, effective vaccine for the virus. The findings were published today in the journal Nature.

The scientists used a novel type of vaccine to immunize mice and monkeys, taking RNA molecules that code for viral proteins (messenger RNA, or mRNA). Because these RNA molecules would usually be quickly cleared by the body, the RNA in the Zika vaccine was modified by the addition of a modified nucleoside. The nucleoside is a nucleotide—the building blocks of DNA—lacking a phosphate group, which previous studies have shown helps to “hide” the mRNA from the host and allow replication. The mRNA was also packaged within lipid nanoparticles, encouraging protein expression. This vaccine therefore allows the mRNA to enter cells and induce production of the viral protein, causing a host immune response similar to that seen with a live virus vaccine. Researchers found that a single dose of the mRNA vaccine effectively protected animals against Zika virus.

Senior author Drew Weissman, of the University of Pennsylvania, relayed the advantages of this approach in a phone call with mental_floss. “The main advantages of our RNA vaccine is that only a single administration is needed. For all of the DNA and inactivated vaccines, they have to immunize twice to get protection, so we get much higher levels of neutralization with a single immunization. The only other vaccine that had protection after a single immunization was the live virus adenovirus vaccine.”

Live vaccines are difficult for a number of reasons, including potential side effects, and cannot be used in pregnant women—a main risk group for Zika infections due to the virus’s effects on the developing fetus. Weissman also noted the mRNA vaccine is inexpensive to produce, which could facilitate widespread use even in resource-limited countries.

Scientists hope to start human clinical trials with the Zika mRNA vaccine in 12 to 18 months. In the interim, additional experiments are planned in order to begin studying whether this Zika vaccine could potentially lead to increased illness with a related flavivirus: dengue. Dengue infection can lead to a phenomenon called “antibody-dependent enhancement,” where antibodies make disease worse instead of protecting the host from infection. There is concern that those vaccinated for Zika could experience more severe dengue infections in areas where both viruses circulate.

To examine whether their Zika vaccine could cause this effect, Weissman says, “We’re taking two approaches. We want to look at antibody-dependent enhancement between different flaviviruses. We’re also working on a combination vaccine that includes all of the flavivirus RNAs together, and the hope there is that with a single vaccine we can immunize against Dengue, West Nile, Zika, Japanese encephalitis, or whatever flaviviruses we want to include.”

Weissman and his collaborators are not the only ones hoping to move a Zika vaccine from the lab to the clinic. A number of different groups have worked to develop a Zika vaccine over the last year. A Phase I clinical trial, to investigate vaccine safety, began last August of a DNA vaccine developed at the National Institutes of Health. And while investigators are hopeful that one of the vaccines in development could be ready for use by 2018, vaccines for pregnant women may be delayed until several years after that, due to the difficulties of demonstrating safety in that population.

The components of the mRNA vaccine also provide hope the vaccine could be used during pregnancy. Weissman explains, “The RNA they use is identical to what’s in our bodies. The nanoparticles also contain mostly physiological lipids. We’ve seen no adverse events from any of our immunizations, so we’re thinking that will probably be easy to give to a pregnant woman.”

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The Real Reason the Lyme Disease Vaccine Had No Shot
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With the potential for causing a variety of lingering symptoms ranging from lethargy to nervous system damage, Lyme disease has become a perennial concern for people venturing outdoors in the summer months. Carried by deer ticks, the Borrelia burgdorferi bacteria can challenge our immune systems and prove frustrating to treat. About 30,000 cases are reported to the CDC each year, although the total cases of unreported transmissions could be ten times that number.

So why don’t we have a vaccine for it? We did. And it disappeared.

According to Vox, the spread of Lyme cases in the 1990s compelled pharmaceutical company GlaxoSmithKline to research and develop a vaccine called LYMErix that attacked the outer protein present in the bacteria. It did so by becoming proactively aggressive, killing off the bacteria while it was still in the body of the attached and feeding tick. More than 1.5 million people were given the vaccine before 2000. Clinical trials demonstrated up to a 90 percent success rate.

While that kind of efficacy and protection would be welcome today, at the time doctors weren’t quite certain what kind of demographic they should be recommending the vaccine to: There was less information about regional areas of tick concentrations than there is now. The vaccine also required three doses in the span of a year, making it slightly inconvenient; some health insurers resisted the $50 cost for each injection.

Those issues were surmountable over time. But some members of the Food and Drug Administration (FDA) panel that had approved the vaccine voiced concern that LYMErix might potentially attack healthy proteins in the body. This autoimmune reaction was never demonstrated in trials, but the theory made consumers wary when it was publicized in the media, and some of those treated complained of arthritis symptoms. Coupled with increasing scrutiny and apprehension over vaccines in general, LYMErix failed to become a staple of vaccination schedules. Sales dropped and GlaxoSmithKline stopped production. With the patent having expired, it’s not likely drug companies will be interested in resurrecting it, only to face additional bad press. Alternative vaccines are being considered, but could take years before coming to market.

In the absence of an effective vaccine, the best way to ward off Lyme remains prevention. If you’re going to be in wooded areas where the ticks tend to congregate, wearing light-colored clothing will help you spot the small nymphs. Insect repellent is important, and examining your body—particularly behind the ears and armpits—for ticks after being outside is also a must. If you find one, remove it with a pair of tweezers.

For more information about Lyme disease, check out our 15 Useful Facts.

[h/t Vox]

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6 Things You Might Not Know About Ebola
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There's been a new outbreak of Ebola in the Democratic Republic of the Congo. Eleven people have been sickened by the disease, and one has died. Here are some things you might not have known about Ebola.

1. THERE'S MORE THAN ONE KIND OF EBOLAVIRUS.

Five species of Ebolavirus have been identified, each named after the place they sprung up: Ebola (formerly Zaire), Bundibugyo, Sudan, Taï Forest, and Reston. All but one—Reston—arose in Africa. The Reston subtype is named after a town in Virginia where an outbreak occurred in 1989, followed by incidents in Texas and Pennsylvania; all three were tied to infected monkeys exported by a single facility in the Philippines. All Ebolavirus species affect people and nonhuman primates—monkeys, gorillas, and chimpanzees—but Reston doesn't cause detectable disease in humans.

2. EBOLA HIJACKS THE IMMUNE SYSTEM.

Researchers are finding out just how clever Ebola is. One key to its lethal success is the stealth way it shuts down immune system defenses, the same way an air force will disable air defenses before sending in the bombers. Ebola obstructs parts of an immune system that are activated by molecules called interferons. These interferons have a vital role in fighting Ebola, usually with scorched-earth tactics such as apoptosis, or cell self-destruction. A 2014 study found that Ebola disables signals the cells use to defend against its attack using a protein called VP24, which binds to a specific protein that takes signaling molecules in and out a cell's nucleus. Blocked from communication, the cell can't call for help or get the order to self-destruct. The virus then hijacks the cell, uses it to make more viruses, and spreads them to more cells. It also produces ebolavirus glycoprotein, which binds to cells inside blood vessels, increasing their permeability and leading to leakage. This contributes to the catastrophic bleeding characteristic of late-stage Ebola infection.

3. BATS ARE THOUGHT TO BE THE KEY HOSTS OF EBOLA.

CDC illustration of cycle of ebola infection from bats to humans and animals

Scientists believe that Ebola's natural host species, or "reservoir hosts," are bats. Infected bats can pass the virus to other mammals, including rats, primates, and us. No one is sure how people first became exposed to Ebola, but the best guess is that monkeys were the conduit. Local hunters in Africa likely became infected while butchering the animals. Anyone who became sick likely infected their family and, if hospitalized in an unsanitary facility, other patients. When the illness spreads from person to person, it does so through direct contact with the bodily fluids of someone who is sick with or has died from Ebola.

4. MEDICAL DETECTIVE WORK IS THE ONLY WAY TO STOP AN EBOLA OUTBREAK.

It takes the investigative skill of a homicide detective to stop an outbreak. Professionals call it contact tracing. Here's how it works: Ebola victim A is isolated and interviewed. Anyone who had close contact with A is put into quarantine for 21 days. If they exhibit no symptoms, they're free to go when the three weeks are up. If they come down with Ebola, they become victim B, and another contact trace begins. If the investigators miss anyone, the outbreak will continue.

5. HAVING MALARIA AND EBOLA AT THE SAME TIME MAY HELP PEOPLE SURVIVE.

Researchers analyzing the the 2014 outbreak of Ebola in West Africa made a surprising finding: patients who had an active malaria parasite infection were actually more likely to survive the Ebola virus, and by a significant degree. While just over half (52 percent) of Ebola patients not infected with malaria survived, those co-infected with malaria had a survival rate of 72 to 83 percent, depending on their ages and the amount of Ebola virus in their blood. The researchers aren't yet sure why, but the prevailing theory is that malaria somehow modifies the immune response to Ebola by toning down a phenomenon called the "cytokine storm"—the body's own response to an Ebola infection, which inadvertently kills the host while attempting to eliminate the pathogen. If malaria can dampen this response, infected patients may have a better chance of surviving.

6. IF YOU'RE A SCIENTIST, YOU CAN ORDER EBOLA ONLINE.

We do not yet have a vaccine or antiviral drug to treat Ebola, but many scientists are working to find one. One source is the National Institute of Allergy and Infectious Diseases (NIAID)'s BEI Resources, which gives research facilities access to microbiological materials called reagents that can help them develop diagnostics and vaccines for emerging diseases, including Ebola. Scientists must be registered with BEI to request materials. Reagents are not active viruses, so they can't spread; on the biosafety level, or BSL, scale—which ranks the severity of infectious disease and sets required safety protocols for working with them in a lab—the Ebola-related reagents are considered BLS 1—the lowest risk. (Live Ebola virus is BLS 4—the highest.) Ordering is limited to one Ebola-related reagent at a time, and can be ordered only twice per year.

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