Research ArticleVaccines

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

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Science Translational Medicine  08 Jan 2020:
Vol. 12, Issue 525, eaav5701
DOI: 10.1126/scitranslmed.aav5701

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Do mother’s antibodies know best?

Infants are susceptible to many infections. One promising strategy to shield them is through vaccination of mothers during pregnancy, thus providing maternal antibodies that can temporarily protect infants from disease. However, maternal antibodies can also prevent infants from developing their own antibody responses that are necessary for long-term protection. Willis et al. now show that an influenza vaccine consisting of nucleoside-modified mRNAs encapsulated in lipid nanoparticles elicited protective antibodies in mouse pups in the presence of maternal antibodies. These authors show that, unlike conventional influenza vaccines, the mRNA vaccine is able to partially overcome the inhibitory effects of maternal antibodies in mouse pups.

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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