Nucleoside-modified mRNA vaccination partially overcomes maternal antibody inhibition of de novo immune responses in mice

核苷修饰的 mRNA 疫苗接种可部分克服母体抗体对小鼠新生免疫反应的抑制

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作者:Elinor Willis, Norbert Pardi, Kaela Parkhouse, Barbara L Mui, Ying K Tam, Drew Weissman, Scott E Hensley

Abstract

Maternal antibodies provide short-term protection to infants against many infections. However, they can inhibit de novo antibody responses in infants elicited by infections or vaccination, leading to increased long-term susceptibility to infectious diseases. Thus, there is a need to develop vaccines that are able to elicit protective immune responses in the presence of antigen-specific maternal antibodies. Here, we used a mouse model to demonstrate that influenza virus-specific maternal antibodies inhibited de novo antibody responses in mouse pups elicited by influenza virus infection or administration of conventional influenza vaccines. We found that a recently developed influenza vaccine, nucleoside-modified mRNA encapsulated in lipid nanoparticles (mRNA-LNP), partially overcame this inhibition by maternal antibodies. The mRNA-LNP influenza vaccine established long-lived germinal centers in the mouse pups and elicited stronger antibody responses than did a conventional influenza vaccine approved for use in humans. Vaccination with mRNA-LNP vaccines may offer a promising strategy for generating robust immune responses in infants in the presence of maternal antibodies.

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