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

Sci Transl Med. 2020 Jan 8;12(525):eaav5701. doi: 10.1126/scitranslmed.aav5701.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies, Viral / immunology
  • Antibody Formation / immunology*
  • Disease Models, Animal
  • Female
  • Germinal Center
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Influenza Vaccines / immunology
  • Lipids / chemistry
  • 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*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Lipids
  • Nucleosides
  • RNA, Messenger