The Immunogenicity of a VLP-based Malaria Vaccine Targeting CSP in Pregnant and Neonatal Mice

Abstract

Maternal antibodies are passively transferred to the fetus via the placenta during gestation and can play an important role in protecting the newborn from infection. For example, in malaria-endemic regions, maternal antibodies likely provide substantial protection against Plasmodium falciparum malaria in the first 6 months of life. However, circulating maternal antibodies can also interfere with vaccine efficacy. Here, we used a mouse maternal transfer model to evaluate whether maternal antibodies interfere with the responsiveness to a virus-like particle (VLP)-based vaccine targeting the CIS43 epitope of the malaria circumsporozoite protein (CSP). We found immunized dams passively transfer to pups high levels of anti-CSP IgG antibodies that steadily decline as the animals age. We also found that the neonatal offspring of immunized mice do not respond to de novo immunization with the CIS43-targeted VLP vaccine until maternal antibody titers decline below an inhibitory threshold. These findings may have important implications for delineating the delicate balance between protection conferred by maternal antibodies and the offspring’s ability to respond to immunization.

Keywords

• maternal antibodies
• neonatal vaccination
• animal models
• malaria vaccines
• circumsporozoite protein