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Sustained early postnatal humoral and cellular immunity against human cytomegalovirus after transamniotic fetal mRNA vaccination in a rodent model
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DOI：10.1016/j.jpedsurg.2025.162544.png)
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Abstract
En 中文
Purpose We sought to examine the humoral and cellular immune responses to transamniotic fetal mRNA vaccination against a human cytomegalovirus (hCMV) antigen over time in early postnatal life in a rodent model. Methods Seven pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 82) of a custom-made mRNA encoding for hCMV envelope glycoprotein-B (hCMV-gB) antigen encapsulated by a lipid-polymer composite on gestational day 17 (E17; term = E21-22). At three time points between 1 and 3 months after birth, serum levels of antigen-specific hCMV-gB IgG antibodies were measured by ELISA. In addition, host spleen lymphocytes were incubated with or without challenge with the hCMV-gB antigen, followed by flow cytometry of culture supernatants to assess T-cell response. Results Overall neonatal survival was 44 % (36/82), with no significant differences between the groups. Antigen-specific hCMV-gB antibodies were present in the serum at all time points, albeit decreasing significantly from 1 to 3 months postnatally (p = 0.029). Spleen lymphocytes from vaccinated pups showed significantly increased production of IFN-gamma, IL-2, TNF-alpha, GM-CSF, and IL-6 following antigen-specific challenge (p = 0.021 to <0.001 vs. non-challenged cells). Cellular response increased significantly over time (p = 0.043 to <0.001), indicating a maturing Th1 response. Conclusions Transamniotic fetal mRNA delivery of a human cytomegalovirus antigen can induce a lasting adaptive cell-mediated immune response, while also exhibiting continued antigen-specific immunoglobulin production extending into the early neonatal period in a healthy rat model. Fetal mRNA vaccination via the minimally invasive transamniotic route may become a practical strategy for the prevention of perinatal infections.
Keywords:
Transamniotic mRNA therapy
Transamniotic fetal immunization
Fetal mRNA immunization
Cytomegalovirus
Transamniotic nucleic acid therapy
TRANAT
mRNA