{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:17:26Z","timestamp":1788499046946,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005627","name":"Thrasher Pediatric Research Fund Early Career Award","doi-asserted-by":"publisher","award":["01433"],"award-info":[{"award-number":["01433"]}],"id":[{"id":"10.13039\/100005627","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Weill Cornell Medicine"},{"id":[{"id":"https:\/\/ror.org\/02r109517","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Weill Cornell R25 Advancing Success and Persistence in Research Education (ASPiRE) program","award":["R25-GM152362"],"award-info":[{"award-number":["R25-GM152362"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Maternal 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. Methods: Adult 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. Results: Spike-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 na\u00efve 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. Conclusions: Using 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.<\/jats:p>","DOI":"10.3390\/vaccines14090769","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:56:01Z","timestamp":1788339361000},"page":"769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunization with mRNA-LNP Elicits De Novo IgG Responses in the Presence of Maternal Antibody"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1233-3909","authenticated-orcid":false,"given":"John M.","family":"Ramos","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Brittany","family":"Plummer","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Christian R.","family":"Binuya","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Mackensie","family":"Gross","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6928-3532","authenticated-orcid":false,"given":"Adelaide S.","family":"Fuller","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-6688","authenticated-orcid":false,"given":"Krithika P.","family":"Karthigeyan","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Savannah","family":"Berrios","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1438-4554","authenticated-orcid":false,"given":"Sallie R.","family":"Permar","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Caitlin A.","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Pediatrics, Weill Cornell Medical College, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Burns, M.D., Muir, C., Atyeo, C., Davis, J.P., Demidkin, S., Akinwunmi, B., Fasano, A., Gray, K.J., Alter, G., and Shook, L.L. 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