Oral DNA vaccination in utero induces mucosal immunity and immune memory in the neonate

Area of Science:

• Immunology
• Neonatal Health
• Vaccine Development

Background:

• Neonatal infectious diseases pose significant mortality risks, often due to vertical pathogen transmission.
• Established pathogens include herpes simplex virus (HSV), human immunodeficiency virus (HIV), hepatitis B virus (HBV), group B Streptococcus, Haemophilus spp., and Chlamydia spp.
• In utero immunization strategies are being explored to protect newborns from early-life infections.

Purpose of the Study:

• To demonstrate immune memory and mucosal immunity in newborn lambs following fetal oral DNA immunization.
• To assess the efficacy of a single in utero oral DNA exposure using bovine herpesvirus-1 glycoprotein D antigen.
• To evaluate the potential of this immunization method in preventing vertical disease transmission.

Main Methods:

• Fetal lambs received a single oral DNA immunization with plasmid encoding bovine herpesvirus-1 glycoprotein D.
• Immune responses (serum Ab titers, cell-mediated immunity, mucosal immunity) were assessed in newborn lambs.
• Immunized lambs were challenged intranasally, and anamnestic responses were evaluated for up to 3 months post-birth.
• Efficacy was also tested using hepatitis B surface antigen (HBsAg).

Main Results:

• 80% of newborn lambs (12/15) showed detectable immune responses after in utero oral DNA immunization.
• Responding lambs exhibited systemic and mucosal immunity, with reduced virus shedding post-challenge.
• Strong anamnestic responses persisted for at least 3 months.
• 75% of lambs immunized with HBsAg achieved protective serum antibody titers.

Conclusions:

• Oral DNA immunization in utero successfully induces both systemic and mucosal immune responses in neonates.
• This immunization method demonstrates potential for preventing vertical transmission of infectious diseases.
• The induction of immune memory suggests long-lasting protection.