Delivering antibodies via mRNA could prevent RSV infection

November 6, 2018, Georgia Institute of Technology
Stitched confocal microscopy image of RSV-infected mouse lung. RSV nucleoprotein and fusion proteins appear red and green, respectively. Cell nuclei appear blue. Credit: Georgia Institute of Technology

Almost every child gets respiratory syncytial virus (RSV), which causes cold-like symptoms. It's usually not a big deal if they're healthy, but every year in the U.S. some 57,000 children under the age of five are hospitalized with the infection. To make matters worse, there's no vaccine and a medication sometimes used to prevent RSV in high-risk children isn't always effective. Now researchers at the Georgia Institute of Technology have developed a promising method of delivering antibodies directly to the lungs, improving their efficacy in warding off RSV.

It was a natural outgrowth of research in his lab, said Philip Santangelo, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. That research focused on using RNA to deliver therapeutic , as well as with the basic virology of RSV. Combining the two was "a logical choice," said Santangelo.

One of the medications used to treat or prevent RSV, the monoclonal antibody palivizumab, is given monthly via intramuscular (IM) injection. Only a small amount of the antibody gets into the airways. "RSV tends to infect airway , as does flu," said Santangelo. "We really didn't see palivizumab there in large quantities. So we thought that was an opportunity."

In a study published October 1 in Nature Communications, Santangelo's team reported using synthetic messenger RNA (mRNA) to deliver antibodies directly to the lungs of mice via aerosol, which the study showed protected them from RSV infection. Two forms of palivizumab were used, the whole secreted form (sPali) and one that was engineered with a glycosylphosphatidylinositol (GPI) membrane anchor or linker (aPali), which should allow it to stay on the epithelial surface longer.

Another group of mice were treated with a different antibody – a VHH camelid antibody, also in secreted and anchored forms – that was previously shown to be more potent than palivizumab but is not currently used to treat RSV.

"With , that may or may not be as critical – we noticed that even with the secreted version we were able to block the virus reasonably well," said Santangelo. "But single-chain antibodies, which are very small, have short half-lives. You have to give them frequently, which doesn't seem practical. When we put this linker on the smaller antibody, we were able to see it on the epithelial cells 28 days later. That was really exciting to us."

In fact, Santangelo suspects that using the linker could cause smaller antibodies to persist for a few months, reducing the need for frequent treatments. "You could see administering this right after a child is born, when they are most vulnerable," he said.

Using mRNA is an effective and safe delivery option, especially crucial in a pediatric population. "Using a transient, nucleic acid-based method that doesn't end up in the cell nucleus is really important," said Santangelo, whose study was funded by a Defense Advanced Research Projects Agency (DARPA) grant and Children's Healthcare of Atlanta. "We do want this to be transient, so if it lasted even a month that would protect newborns in the hospital where they may be exposed to RSV. And if you could protect kids for a few months at a time, that's really all you would need to do."

The study found that most of the mRNA-expressed antibodies did not change baseline levels of cytokines, indicating that the approach was minimally inflammatory and suggesting that repeat dosing could be considered.

It's also possible that the antibodies used in this study could potentially neutralize the virus in cells, so even if a child was infected the severity of symptoms might be lessened. And RSV isn't the only potential virus this method could target – Santangelo is currently working on a project that targets flu via dry powder delivery of mRNA. That project is supported by the Bill & Melinda Gates Foundation.

With the promising results from the RSV study, Santangelo hopes to move from a mouse model to additional testing. "There's more work to be done," he said. "The use of antibodies for preventing infection is a huge deal right now. But even if you found this potent antibody, if you can't deliver it where it needs to go then the efficacy may not be where you want it to be. At least with the lung, we know where we want to go, and IV or IM administration isn't really ideal for the cell types that are most critical for RSV."

Explore further: Team isolates antibodies that neutralize GI bug norovirus

More information: Pooja Munnilal Tiwari et al. Engineered mRNA-expressed antibodies prevent respiratory syncytial virus infection, Nature Communications (2018). DOI: 10.1038/s41467-018-06508-3

Related Stories

Team isolates antibodies that neutralize GI bug norovirus

August 31, 2018
Researchers at Vanderbilt University Medical Center have isolated the first human monoclonal antibodies that can neutralize norovirus, the leading cause of acute gastrointestinal illness in the world.

Researchers reveal new way to potentially fight Ebola

March 6, 2018
More than 11,000 people died during the Ebola outbreak in West Africa from 2013-16, demonstrating both the deadly nature of the virus and the limitations of the medication used to fight it.

Study offers clues to making vaccine for infant respiratory illness

April 25, 2013
An atomic-level snapshot of a respiratory syncytial virus (RSV) protein bound to a human antibody represents a leap toward developing a vaccine for a common—and sometimes very serious—childhood disease. The findings, ...

T cell-inducing dengue vaccines may better protect children of vaccinated mothers

December 22, 2017
For a long time, a dengue vaccine was the holy grail in dengue research. Now that a dengue vaccine is finally on the market (Sanofi's Dengvaxia), other issues have arisen, such as what happens in the babies of vaccinated ...

Powerful RNA-based technology could help shape the future of therapeutic antibodies

March 2, 2017
Using antibodies to treat disease has been one of the great success stories of early 21st-century medicine. Already five of the ten top-selling pharmaceuticals in the United States are antibody products. But antibodies are ...

How antibodies access neurons to fight infection

May 18, 2016
Yale scientists have solved a puzzle of the immune system—how antibodies enter the nervous system to control viral infections. Their finding may have implications for the prevention and treatment of a range of conditions, ...

Recommended for you

Infants born to obese mothers risk developing liver disease, obesity

November 16, 2018
Infant gut microbes altered by their mother's obesity can cause inflammation and other major changes within the baby, increasing the risk of obesity and non-alcoholic fatty liver disease later in life, according to researchers ...

New study shows NKT cell subsets play a large role in the advancement of NAFLD

November 16, 2018
Since 2015 it has been known that the gut microbiota could have a direct impact on nonalcoholic fatty liver disease (NAFLD), which affects up to 12% of adults and is a leading cause of chronic liver disease. In the November ...

Antibiotic prescribing influenced by team dynamics within hospitals

November 15, 2018
Antibiotic prescribing by doctors is influenced by team dynamics and cultures within hospitals.

Discovery suggests new route to fight infection, disease

November 14, 2018
New research reveals how a single protein interferes with the immune system when exposed to the bacterium that causes Legionnaires' disease, findings that could have broad implications for development of medicines to fight ...

Zika may hijack mother-fetus immunity route

November 14, 2018
To cross the placenta, Zika virus may hijack the route by which acquired immunity is transferred from mother to fetus, new research suggests.

New research aims to help improve uptake of hepatitis C testing

November 14, 2018
New research published in Scientific Reports shows persisting fears about HIV infection may impact testing uptake for the hepatitis C Virus (HCV).

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Nov 07, 2018
God bless Dr Larry for his marvelous work in my life, I was diagnosed of HERPES SIMPLEX VIRUS since 2010 and I was taking my medications, I wasn't satisfied i needed to get the HERPES out of my system, I searched about some possible cure for HERPES i saw a comment about Dr Larry, how he cured HERPES with his herbal medicine, I contacted him and he guided me. I asked for solutions, he started the remedy for my health, he sent me the medicine within 3days. I took the medicine as prescribed by him and 2weeks later i was cured from HERPES contact him once again thanks to you Dr Larry. cure the flowing virus, contact his web site: or add him on whatsapp +1(424)-261-8520
1 cancer cure
2 diabetes cure
3 ringing ear
4 herpes cure
5 warts cure
6 HPV cure
8 get your ex back
9 pregnancy herbal medicine
10 prostate enlargement
11 Hepatitis

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.