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Vaccination with the RSV fusion protein formulated with a combination adjuvant induces long-lasting protective

R Garg1, L Latimer1, V Gerdts1,2

  • 1VIDO-Intervac, University of Saskatchewan, Saskatoon, SK, S7N 5E3, Canada.

The Journal of General Virology
|February 28, 2014
PubMed

Insights

This study shows that a novel Respiratory Syncytial Virus (RSV) vaccine, ΔF/TriAdj, provides at least one year of protection in mice. The vaccine induced robust immune responses and prevented RSV replication without causing harm.

Area of Science:

  • Immunology
  • Vaccinology
  • Virology

Background:

  • Respiratory Syncytial Virus (RSV) is a major cause of respiratory infections in infants.
  • A previously developed RSV vaccine candidate, ΔF/TriAdj, combines a truncated F protein with Toll-like receptor (TLR) agonists.
  • Understanding the duration of immunity conferred by this vaccine is crucial for its clinical development.

Purpose of the Study:

  • To evaluate the long-term protective efficacy and duration of immunity induced by the ΔF/TriAdj RSV vaccine candidate.
  • To compare the immunogenicity of two formulations: ΔF/TriAdj with polyinosinic:polycytidylic acid (polyI:C) versus cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs).

Main Methods:

  • Mice were intranasally immunized with ΔF/TriAdj formulations containing either polyI:C or CpG ODNs.
  • Long-term immunity was assessed one year after the second vaccination by challenging mice with RSV.
  • Humoral (IgG, IgA) and cellular (T cells, cytokine production) immune responses were analyzed.

Main Results:

  • Both ΔF/TriAdj formulations induced high levels of virus-neutralizing antibodies and IgA in the lungs.
  • A T-helper cell type 1 (Th1)-biased immune response was observed, with induction of RSV-specific CD8(+) T cells.
  • The polyI:C formulation showed enhanced IgG affinity maturation and higher numbers of memory CD8(+) T cells compared to the CpG formulation.
  • No virus replication or vaccine-induced pathology was detected in any immunized mice after RSV challenge.

Conclusions:

  • The ΔF/TriAdj RSV vaccine formulations provide at least one year of protective immunity in a mouse model.
  • Both polyI:C and CpG adjuvants induce robust and protective immune responses against RSV.
  • The ΔF/TriAdj(polyI:C) formulation demonstrated superior induction of antibody affinity and T cell memory.

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