Sustained early postnatal humoral and cellular immunity against human cytomegalovirus after transamniotic fetal mRNA vaccination in a rodent model.

作者信息

Scire Emily M, Huang Alex L, Boccia Thais, Moskowitzova Kamila, Kycia Ina, Dang Tanya T, Tai Melody, Zacharakis Eva, Aihara Ayaka, Bechara Beatriz S, Zurakowski David, Fauza Dario O

机构信息

Departments of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.

出版信息

J Pediatr Surg. 2025 Aug 12:162544. doi: 10.1016/j.jpedsurg.2025.162544.

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-γ, IL-2, TNF-α, 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.

LEVEL OF EVIDENCE

N/A.

TYPE OF STUDY

Animal and laboratory study.