Targeting pregnant women against malaria through vaccination could protect infants.

While developing a malaria vaccine has become a global public health priority, the first vaccine to reach Phase 3 trials and licensure (RTS.S) has been less effective in infants compared to older children, suggesting that an alternative approach is needed to protect this most vulnerable age group.

Research conducted by University of Maryland School of Medicine in Malawi showed the potential for protecting infants from malaria before they are born by vaccinating pregnant women. Led by Miriam Laufer, MD, MPH, Director of UM SOM’s Division of Malaria Research, researchers studied the transfer of antibodies from mother to fetus in 33 mother-infant pairs. Using a unique microarray approach developed by UM SOM they were able to determine that the full range of antibodies that the mother has against malaria are passed to her infant prior to delivery.

It is known that antibodies in a pregnant woman’s blood pass across the placenta into the fetus, giving the baby some protection against infections at birth. But what UM SOM researchers discovered in their research published in Clinical and Vaccine Immunology is that mother and infants had the same repertoire of antibodies to malaria. What this means is that an infant’s antibodies can recognize the same range of malaria surface proteins. This is critical because malaria parasites have different forms of surface proteins that they can express, and in order to be protected against malaria infections, the immune system must recognize several different forms of each of the proteins.

Furthermore, the research showed that malaria infection in the placenta did not interfere with the passage of antibodies across the placenta.

“Our research shows that if we boost the mother’s immune responses to malaria, such as through vaccination, the infant will be better protected against infection,” said Dr. Laufer. “This is critical because young children are at highest risk of dying from infectious diseases such as malaria. In addition, if we can prevent infection during infancy, this may help ensure healthy growth and cognitive development in infants and young children.”

The research in Malawi, followed pregnant women from 20-26 weeks into gestation through delivery. This included monthly routine visits and evaluations when they were sick. Researchers collected specimens from mothers and from the umbilical cord attached to the placenta at delivery. Using the serum they collected, they were able to map the antibody responses malaria surface proteins that were present in both the mother and infant, using a unique microarray platform.

"Our study underscores the importance of reaching out to women during pregnancy. This is a rare time when adults regularly encounter the healthcare system and interventions introduced during pregnancy have the potential to improve the health of both the mother and child," said Sarah Boudova, PhD, an UM SOM researcher in the Division of Malaria Research and lead author of the research paper.

It is the first study to employ this high throughput protein microarray to compare maternal and newborn responses, allowing researchers to analyze infant blood serum reactions to a large and diverse group of potential vaccine antigens and thoroughly characterize the effectiveness of trans-placental antibody transfer.

Typically, when researchers look at immune response to malaria, they use malaria parasites that have been adapted to grow in the laboratory. However, these are not necessarily similar to the parasites seen in nature. This is why past vaccine developments using laboratory strains of malaria have not been effective in protecting against a wide range of malaria strains. This led UM SOM the research team to create platforms to characterize the diversity of malaria parasite surface antigens through genomic tools and devel