Neonatal mice immune response to COVID-19 mRNA vaccine

Leda Lotspeich-Cole1, Mukesh Kumar Jha1, Swetha Parvathaneni1

  • 1US FDA/CBER/OVRR/DBPAP, 10903 New Hampshire Ave., Silver Spring, MD, USA.

Vaccine
|January 29, 2026
PubMed

Insights

The mRNA vaccine platform generated higher antibody levels and better SARS-CoV-2 binding inhibition in neonatal mice compared to recombinant protein vaccines. This suggests mRNA vaccines may offer superior immunogenicity in young populations.

Area of Science:

  • Immunology
  • Vaccinology
  • Molecular Biology

Background:

  • The COVID-19 pandemic saw the first licensing of mRNA vaccines for human use.
  • Current mRNA vaccines for SARS-CoV-2 are not authorized for neonates, necessitating research into their safety and efficacy in this demographic.
  • Limited data exists on the immunogenicity of SARS-CoV-2 mRNA vaccines in neonatal populations.

Purpose of the Study:

  • To compare the immunogenicity of mRNA-encoded receptor binding domain (RBD) vaccines versus recombinant RBD protein vaccines in neonatal mice.
  • To evaluate the antibody responses and functional capacity, specifically the inhibition of RBD binding to ACE2, induced by these two vaccine platforms in neonates.

Main Methods:

  • Neonatal mice were immunized twice, three weeks apart, with either an mRNA-encoded RBD vaccine (RBD-mRNA-LNP) or a recombinant RBD protein vaccine (rRBD) adjuvanted with AddaVax™.
  • Antibody levels, specifically IgG against RBD, were quantified.
  • The functional capability of the induced antibodies was assessed by measuring the inhibition of RBD binding to the ACE2 receptor.

Main Results:

  • Both vaccine platforms induced detectable anti-RBD antibodies in neonatal mice.
  • The RBD-mRNA-LNP vaccine elicited significantly higher levels of IgG antibodies against RBD compared to the rRBD vaccine.
  • Immunization with the RBD-mRNA-LNP vaccine resulted in more potent inhibition of RBD binding to ACE2.

Conclusions:

  • The mRNA vaccine platform demonstrates superior immunogenicity in neonatal mice compared to the recombinant protein platform.
  • mRNA vaccines elicit higher antibody titers and enhanced functional activity, including improved inhibition of viral binding, in neonatal models.
  • These findings suggest the potential of mRNA vaccine technology for inducing robust immune responses in very young individuals, warranting further investigation.

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