Summary auto-generated
This study evaluated whether replication-defective adenoviruses delivering the pseudorabies virus (PRV) glycoprotein gD gene could overcome maternal antibody interference in vaccinating newborn piglets. Researchers vaccinated 1-day-old piglets from both vaccinated (immune) and unvaccinated (naive) dams with either naked plasmid DNA or recombinant adenovirus carrying the gD gene, followed by a live PRV vaccine booster at 10 weeks. All animals were challenged with virulent PRV at 16 weeks. Adenovirus-mediated gene transfer successfully primed piglets born to immune dams, enabling them to mount protective immune responses comparable to unprimed piglets from naive dams after the booster vaccination. In contrast, naked DNA priming failed to overcome maternal antibody inhibition. Following challenge, adenovirus-primed piglets from immune dams achieved protection levels similar to conventionally vaccinated naive piglets. The findings suggest that replication-defective adenovirus vectors can effectively deliver immunogenic genes in the presence of maternal antibodies, offering a practical approach for early vaccination of neonates born to previously vaccinated or infected mothers.
Key findings
- Replication-defective adenovirus-mediated delivery of PRV gD gene successfully primed newborn piglets born to vaccinated dams, overcoming maternal antibody interference
- Naked plasmid DNA delivery of the same gD gene failed to prime piglets against maternal antibodies, despite using 10-fold higher gene copy numbers than adenovirus delivery
- Adenovirus-primed piglets from immune dams developed neutralizing antibody responses after booster vaccination and achieved equivalent protection against virulent PRV challenge as unprimed piglets from naive dams
- The superior efficacy of adenovirus versus plasmid delivery likely reflects greater transduction of antigen-presenting cells and higher-level gene expression in vivo
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Abstract
One of the main limitations of the vaccination of neonates from vaccinated or infected mothers is the interference by inherited maternal antibodies, which are known to inhibit the immune response against both live and inactivated vaccines. The efficiency of bypassing this inhibition by the transfer of an immunogenic glycoprotein gene, the gD gene of pseudorabies virus (PRV), into neonates was explored. The experiments were conducted in 1-day-old piglets, which are immunocompetent at birth. The same transcription unit (gD of PRV under the control of the adenovirus major late promoter) was delivered intramuscularly at birth either in the form of naked DNA or cloned in the genome of a replication-defective adenovirus. A booster injection of a conventional live PRV vaccine strain was given at 10 weeks of age, the replication of which was greatly restricted by the residual amounts of colostral antibodies in control animals. Piglets were challenged at the age of 16 weeks with a virulent PRV strain. The replication- defective adenovirus was able to efficiently prime piglets born to immune dams against gD in such a way that inoculation with the Bartha strain protected them against a subsequent challenge with the same level of efficacy in piglets born to naive or immune dams. In contrast, piglets born to immune dams into which the gD gene was not transferred, or transferred as naked DNA at birth, were not protected. These results open the way for early immunization of neonates born to vaccinated or infected mothers.