ArticleVaccines2026
Immunization with mRNA-LNP Elicits De Novo IgG Responses in the Presence of Maternal Antibody.
Article in Vaccines, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
Funding
Abstract
BACKGROUND/
objectivesMaternal antibodies can inhibit vaccine-specific humoral responses in early life, leaving infants at increased risk for severe disease for vaccine-preventable infections. In the case of SARS-CoV-2, infants under the age of 3 months represented most child hospitalizations, yet there is no approved vaccine for children under the age of 6 months. There is a clear need for effective immunization in early life to prevent infant morbidity and mortality. Here, we established a mouse model to define how maternally derived antibodies shape early-life responses to mRNA vaccination.
methodsAdult female mice were immunized with PBS or 5 mcg of the SARS-CoV-2 mRNA-1273 vaccine via intramuscular injection and paired with a male. Pups from subsequent litters were immunized with PBS or 5 mcg of mRNA-1273 vaccine via intramuscular injection. Peripheral blood and spleens were collected at time points post-immunization. We measured vaccine-elicited anti-Spike IgG in mouse pups exposed or unexposed to vaccine-specific maternal IgG.
resultsSpike-specific maternal IgG is detectable at high levels immediately after pup immunization or mock immunization; however, in mock immunized pups, it wanes by three weeks post-pup immunization. Pups born to immunized dams developed Spike specific IgG comparable to pups born to naïve dams. IgG subclass analyses distinguished passively acquired antibodies from vaccine-induced responses. Despite robust binding antibody responses, neutralizing activity against D614G pseudovirus was heterogeneous and did not scale proportionally with IgG titers, showing qualitative differences in early-life humoral immunity. Splenic Spike-specific B cell frequencies and T follicular helper (Tfh) cell responses were detectable in vaccinated pups irrespective of maternal immunization status, with Tfh cell frequencies peaking at day 7 post-immunization in both groups.
conclusionsUsing SARS-CoV-2 as a model pathogen, we found that early-life mRNA vaccination can elicit humoral immune responses in the presence of maternal antibodies. Furthermore, the presence of maternal antibody did not inhibit the development of antigen-specific B cells or Tfh cells in the spleen. Our findings support the potential of extending vaccination strategies into early infancy and provide a framework for optimizing mRNA-based vaccine timing and design in the context of maternal immunity.
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