Journal
VACCINE
Volume 25, Issue 41, Pages 7132-7144Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2007.07.065
Keywords
respiratory syncytial virus; vaccine; Venezuelan equine encephalitis virus; alphavirus; replicons; BALB/c mice; rhesus macaques; balanced immune responses; bronchoalveolar lavage
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Respiratory syncytial virus (RSV) is a major cause of acute respiratory tract disease in humans. Towards development of a prophylactic vaccine, we genetically engineered Venezuelan equine encephalitis virus (VEEV) replicons encoding the fusion (Fa) or attachment (Cia or Cib) proteins of the A or B subgroups of RSV. Intramuscular immunization with a formulation composed of equal amounts of each replicon particle (3vRSV replicon vaccine) generated serum neutralizing antibodies against A and B strains of RSV in BALB/c mice and rhesus macaques. When contrasted with purified natural protein or formalin-inactivated RSV formulated with alum, the 3vRSV replicon vaccine induced balanced Th1/Th2 T cell responses in mice. This was evident in the increased number of RSV-specific IFN-gamma(divided by) splenocytes following F or G peptide stimulation, diminished quantity of eosinophils and type 2 T cell cytokines in the lungs after challenge. and increased in vivo lysis of RSV peptide-loaded target cells. The immune responses in mice were also protective against intranasal challenge with RSV. Thus, the replicon-based platform represents a promising new strategy for vaccines against RSV. (c) 2007 Elsevier Ltd. All rights reserved.
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