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. 2000 Nov;74(22):10287-92.
doi: 10.1128/jvi.74.22.10287-10292.2000.

Efficacy and safety studies of a recombinant chimeric respiratory syncytial virus FG glycoprotein vaccine in cotton rats

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Efficacy and safety studies of a recombinant chimeric respiratory syncytial virus FG glycoprotein vaccine in cotton rats

G A Prince et al. J Virol. 2000 Nov.

Abstract

Several formulations of a recombinant chimeric respiratory syncytial virus (RSV) vaccine consisting of the extramembrane domains of the F and G glycoproteins (FG) were tested in cotton rats to evaluate efficacy and safety. The FG vaccine was highly immunogenic, providing nearly complete resistance to pulmonary infection at doses as low as 25 ng in spite of inducing relatively low levels of serum neutralizing antibody at low vaccine doses. Upon RSV challenge animals primed with FG vaccine showed quite mild alveolitis and interstitial pneumonitis, which were eliminated by the addition of monophosphoryl lipid A to the formulation.

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Figures

FIG. 1
FIG. 1
Neutralizing antibody response of cotton rats to various doses of recombinant chimeric FG RSV vaccine after one or two doses, with the geometric mean ± the SE and five animals per dosage level.
FIG. 2
FIG. 2
Pulmonary viral titers in cotton rats immunized with two doses of various amounts of recombinant chimeric FG RSV vaccine as shown in Fig. 1, challenged with RSV and sacrificed 5 days after challenge, with the geometric mean ± the SE (n = 5 cotton rats per dosage level).
FIG. 3
FIG. 3
Neutralizing antibody titers in cotton rats after one or two 25-ng doses of various formulations of RSV recombinant chimeric FG vaccine, formalin-inactivated whole-virus RSV vaccine, or infection with live virus, with the geometric mean ± the standard deviation (n = 10 cotton rats per treatment).
FIG. 4
FIG. 4
Pulmonary virus titers in cotton rats after two 25-ng doses of various formulations of RSV recombinant chimeric FG vaccine, formalin-inactivated whole-virus RSV vaccine, or infection with live virus, followed by live-virus challenge, with the geometric mean ± the SE (n = 3 to 4 cotton rats per treatment and day of sacrifice).
FIG. 5
FIG. 5
Peribronchiolitis in cotton rats after two 25-ng doses of various formulations of RSV recombinant chimeric FG vaccine, formalin-inactivated whole-virus RSV vaccine, or infection with live virus, followed by live-virus challenge, with the arithmetic mean ± the SE (n = 3 to 4 cotton rats per treatment and day of sacrifice).
FIG. 6
FIG. 6
Alveolitis in cotton rats after two 25-ng doses of various formulations of RSV recombinant chimeric FG vaccine, formalin-inactivated whole-virus RSV vaccine, or infection with live virus, followed by live-virus challenge, with the arithmetic mean ± the SE (n = 3 to 4 cotton rats per treatment and day of sacrifice).
FIG. 7
FIG. 7
(A) Lack of alveolitis in a cotton rat immunized twice with 25 ng of recombinant chimeric FG RSV vaccine, to which MPL was added, and challenged with RSV 5 days previously. The alveoli are indistinguishable from those in unmanipulated animals or those with a primary RSV infection. (B) Very mild alveolitis in a cotton rat immunized twice with 25 ng of recombinant chimeric FG RSV vaccine without MPL and challenged with RSV 5 days previously. (C) Alveolitis in a cotton rat immunized with formalin-inactivated RSV vaccine and challenged with RSV 5 days previously. Cells, predominantly polymorphonuclear leukocytes, are free in the alveolar space, and the alveolar walls are thickened. Samples were H&E stained. Magnification, ×140.

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