Maternal immunization with respiratory syncytial virus fusion protein formulated with a novel combination adjuvant provides protection from RSV in newborn lambs

Vaccine. 2016 Jan 4;34(2):261-269. doi: 10.1016/j.vaccine.2015.11.029. Epub 2015 Nov 24.

Abstract

Respiratory syncytial virus (RSV) is the causative agent of serious upper and lower respiratory tract infections in newborns and infants. Protection from RSV is crucial for neonates, and maternal immunization is one approach that holds promise for providing immediate protection to young infants against severe RSV infection. We previously reported efficacy of a subunit vaccine consisting of the fusion (F) protein formulated with a novel adjuvant (ΔF/TriAdj) in neonates. The goal of the current study was to evaluate the ΔF/TriAdj as a maternal vaccine. Pregnant ewes were vaccinated intramuscularly with ΔF/TriAdj or PBS six weeks prior to lambing, and re-vaccinated four weeks later, which resulted in transfer of maternal antibodies (MatAbs) to the newborn lambs through the colostrum. Significantly higher levels of RSV ΔF-specific serum IgG were detected in vaccinated pregnant ewes and their lambs when compared to control animals, which revealed that MatAbs were passively transferred to the offspring. All newborn lambs were challenged with RSV at three days of age. After RSV challenge, virus production and lung pathology were significantly lower in lambs that had received passively transferred antibodies than in control animals. These results indicate that maternal immunization with ΔF/TriAdj might be an alternative, safe and effective approach to provide protection against RSV in newborn and young infants.

Keywords: Animal model; Maternal antibodies; Maternal immunization; Newborn lambs; Protection; RSV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Animals, Newborn
  • Antibodies, Viral / blood
  • Female
  • Immunity, Maternally-Acquired*
  • Immunoglobulin G / blood
  • Injections, Intramuscular
  • Lung / pathology
  • Lung / virology
  • Pregnancy
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Respiratory Syncytial Virus Infections / prevention & control
  • Respiratory Syncytial Virus Infections / veterinary*
  • Respiratory Syncytial Virus Vaccines / administration & dosage
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Viruses / immunology*
  • Sheep
  • Sheep Diseases / prevention & control*
  • Treatment Outcome
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • Respiratory Syncytial Virus Vaccines
  • Vaccines, Synthetic