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

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...

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Bibliographic Details
Published in:Science translational medicine Vol. 12; no. 525
Main Authors: Willis, Elinor, Pardi, Norbert, Parkhouse, Kaela, Mui, Barbara L, Tam, Ying K, Weissman, Drew, Hensley, Scott E
Format: Journal Article
Language:English
Published: United States 08.01.2020
Subjects:
Adjuvants, Immunologic - pharmacology
Animals
Antibodies, Viral - immunology
Antibody Formation - immunology
Disease Models, Animal
Female
Germinal Center
Hemagglutinin Glycoproteins, Influenza Virus - immunology
Influenza Vaccines - immunology
Lipids - chemistry
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nanoparticles - chemistry
Nucleosides - metabolism
Orthomyxoviridae - immunology
Orthomyxoviridae Infections - immunology
Orthomyxoviridae Infections - prevention & control
Orthomyxoviridae Infections - virology
RNA, Messenger - immunology
Vaccination
ISSN:1946-6242, 1946-6242
Online Access:Get more information
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Summary: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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ISSN:1946-6242
1946-6242
DOI:10.1126/scitranslmed.aav5701