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Study paves way for new vaccines to protect infants against infections

An mRNA vaccine has been developed which has elicited strong immune responses in mice in the presence of maternal antibodies.

Vaccines that can protect infants against infections by overcoming a mother’s antibodies, which are known to shut down immune defences initiated by conventional vaccines, could now be possible due to a new study. 

The study’s researchers found that a specialised modified-RNA (mRNA) influenza vaccine successfully protected young mice against the infection in the presence of maternal antibodies. The study suggests this protection occurred because the vaccine programmes cells to constantly release new antigens for a prolonged period of time, rather than delivering a one-time shot of a viral protein.

Maternal antibodies are kind of a double-edged sword”

The research team from Penn Medicine, US were led by Scott E Hensley, PhD, an associate professor of Microbiology and Drew Weissman, MD, PhD, a professor of Infectious Diseases in the Perelman School of Medicine at the University of Pennsylvania, US. 

“Around the world, every year, many young infants become infected and often die from infections because of a lack of effective vaccines to protect them earlier in life,” Weissman said. “mRNA-based vaccines could potentially help prevent that. What’s more, it would not only be effective against influenza but also other pathogens, as the vaccine’s platform is easily adaptable to different antigens.”

Developing effective vaccines that protect infants in the presence of maternal antibodies has proven difficult because the antibodies can bind to vaccines and prevent them from eliciting good immune responses, the researchers said.

“Maternal antibodies are kind of a double-edged sword: they are great to have around when you are young because they can protect you from infection, but it’s tough to vaccinate when there are high levels of them,” Hensley explained. “Today’s strategy is to wait awhile for these antibodies to decline. This isn’t ideal because the timing can be imprecise, so there is almost always a period where the young infant is susceptible to disease.”

For this study, the Penn lab turned to what is known as a nucleoside-modified mRNA encapsulated in lipid nanoparticles (mRNA-LNP) vaccine. To determine its ability to overcome maternal antibodies, the researchers first established a mouse model to show how the antibodies protect young mice against influenza and how they inhibit immune responses elicited by conventional vaccinations.

…this protection occurred because the vaccine programmes cells to constantly release new antigens”

Next, the researchers tested the mRNA vaccine platform in the mouse model and found that it elicited strong antibody responses, both in the presence and absence of maternal antibodies and protected the mice from the virus.

The vaccine essentially “slips under the radar,” Hensley said, gets into cells and then starts continuously producing the antigen for the immune system to respond to in what’s called “prolonged germinal center reactions.” The findings suggest that maternal antibodies eventually drop below a certain level and the antigen is still there to generate an immune response from the child.

The preclinical study was published online in Science Translational Medicine.

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