Xm. Li et al., PROTECTION AGAINST RESPIRATORY SYNCYTIAL VIRUS-INFECTION BY DNA IMMUNIZATION, The Journal of experimental medicine, 188(4), 1998, pp. 681-688
Respiratory syncytial virus (RSV) remains a major cause of morbidity a
nd mortality in infants and dir elderly and is a continuing challenge
for vaccine development. A murine T helper cell (Th) type 2 response a
ssociates with enhanced lung pathology, which has been observed in pas
t infant trials using formalin-inactivated RSV vaccine. In this study,
we have engineered an optimized plasmid DNA vector expressing the RSV
fusion (F) protein (DNA-F). DNA-F was as effective as Live RSV in mic
e at inducing neutralizing antibody and cytotoxic T lymphocyte respons
es, protection against infection, and high mRNA expression of lung int
erferon gamma after viral challenge. Furthermore, a DNA-F boost could
switch a preestablished anti-RSV Th2 response towards a Th1 response.
Critical elements for the optimization of the plasmid constructs inclu
ded expression of a secretory form of the F protein and the presence o
f the rabbit P-globin intron II sequence upstream of the F-encoding se
quence. In addition, anti-F systemic immune response profile could be
modulated by the route of DNA-F delivery: intramuscular immunization r
esulted in balanced responses, whereas intradermal immunization result
ed in a Th2 type of response. Thus, DNA-F immunization may provide a n
ovel and promising RSV vaccination strategy.