mRNA Vaccine Elicited Strong Immune Responses in the Presence of Maternal Antibodies

A preclinical Perelman School of Medicine at the University of Pennsylvania study puts researchers closer to developing vaccines that can protect infants against infections by overcoming a mother’s antibodies, which are known to shut down immune defenses initiated by conventional vaccines.

That immune system issue largely explains why vaccinations for infectious diseases like influenza and measles are not given until 6 to 12 months of age. 

This new study published in Science Translational Medicine on January 8, 2020, found that a specialized modified-RNA (mRNA) influenza vaccine successfully protected young mice against the infection in the presence of maternal antibodies. 

This study suggests this protection occurred because the vaccine programs allowed cells to constantly churn out new antigens for a prolonged period of time, rather than delivering a one-time shot of a viral protein.

“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,” said Drew Weissman, M.D., Ph.D., a professor of Infectious Diseases in the Perelman School of Medicine at the University of Pennsylvania, in a press release.

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.

“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.”

mRNA vaccines have emerged as leading candidates for protection against pathogens in adult clinical studies. 

Instead of delivering lab-grown viral proteins like a traditional vaccine, mRNA vaccines introduce an mRNA sequence that program cells to produce antigens to mimic the disease. 

The result is a more powerful immune response and broader protection.

For this study, the Penn lab turned to what is known as a nucleoside-modified mRNA encapsulated in the lipid nanoparticles (mRNA-LNP) vaccine. 

Previously, these Penn researchers showed that this vaccine, which expresses hemagglutinin (HA) proteins, elicited robust antibody responses and protected adult animals from influenza.

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. 

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

The finding suggests that maternal antibodies eventually drop below a certain level and the antigen is still there to generate an immune response from the child.

“Imagine a world where an infant is born or comes into the clinic very early in life and can receive vaccines that have antigens not just for the flu, but a multitude of different pathogens.”

“Wouldn’t that be something,” concluded these researchers.

Co-authors on the paper include Norbert Pardi and Kaela Parkhouse from Penn and Barbara L. Mui and Ying K. Tam from Acuitas.

With the founding of the nation’s first hospital, Pennsylvania Hospital, in 1751 and the nation's first medical school at the University of Pennsylvania in 1765, Penn Medicine has pioneered medical frontiers with a staff comprised of innovators who have dedicated their lives to advancing medicine through excellence in education, research and patient care.

This vaccine study was funded in part by the Burroughs Wellcome Fund and the National Institute of Allergy and Infectious Disease (R01AI113047, R01AI108686, R01-AI050484, R01-AI124429, R01-AI084860, T32-AI070077, T32-AI055428). No conflicts of interest were disclosed.

Vaccine news published by Precision Vaccinations.