DNA vaccination in utero: a new approach to induce protective immunity in the newborn

Area of Science:

• Immunology
• Neonatal Health
• Vaccinology

Background:

• Infectious diseases are a major cause of neonatal mortality globally.
• Transmission of pathogens like herpes simplex virus (HSV) and group B Streptococcus (GBS) to newborns often occurs late in pregnancy, during birth, or via breastfeeding.
• Active immunization of the fetus presents a potential strategy to mitigate neonatal disease risk.

Purpose of the Study:

• To evaluate the safety and efficacy of in utero DNA immunization in fetal lambs.
• To assess the impact of fetal immunization on gestation, neonatal viability, and leukocyte populations.
• To determine if in utero immunization induces protective mucosal immunity, immune memory, or immune tolerance.

Main Methods:

• DNA immunization was administered in utero to fetal lambs during the third trimester of gestation.
• Post-immunization assessments included fetal gestation, neonatal viability, blood leukocyte counts, and immune responses.
• Immune memory and tolerance were evaluated in newborn lambs.

Main Results:

• In utero immunization was found to be safe, with no adverse effects on fetal gestation, neonatal viability, or significant alterations in leukocyte populations.
• The procedure successfully induced protective mucosal immunity and immune memory in newborn lambs.
• No evidence of immune tolerance was observed following in utero DNA immunization.
• Plasmid DNA uptake and expression were detected in the oral cavity epithelium, correlating with localized immune responses.

Conclusions:

• In utero DNA immunization is a safe and effective method for inducing protective immunity in newborns.
• This approach establishes immune memory and mucosal immunity, crucial for combating neonatal infections.
• The findings support the potential of fetal immunization as a novel strategy to reduce neonatal morbidity and mortality from infectious diseases.