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Clinical Trial
. 2008 Nov 25;26(50):6338-43.
doi: 10.1016/j.vaccine.2008.09.026. Epub 2008 Sep 26.

A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial

Julie E Martin  1 , Mark K Louder, LaSonji A Holman, Ingelise J Gordon, Mary E Enama, Brenda D Larkin, Charla A Andrews, Leatrice Vogel, Richard A Koup, Mario Roederer, Robert T Bailer, Phillip L Gomez, Martha Nason, John R Mascola, Gary J Nabel, Barney S Graham; VRC 301 Study Team
Collaborators, Affiliations
Clinical Trial

A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial

Julie E Martin et al. Vaccine. .

Abstract

Background: The severe acute respiratory syndrome (SARS) virus is a member of the Coronaviridae (CoV) family that first appeared in the Guangdong Province of China in 2002 and was recognized as an emerging infectious disease in March 2003. Over 8000 cases and 900 deaths occurred during the epidemic. We report the safety and immunogenicity of a SARS DNA vaccine in a Phase I human study.

Methods: A single-plasmid DNA vaccine encoding the Spike (S) glycoprotein was evaluated in 10 healthy adults. Nine subjects completed the 3 dose vaccination schedule and were evaluated for vaccine safety and immune responses. Immune response was assessed by intracellular cytokine staining (ICS), ELISpot, ELISA, and neutralization assays.

Results: The vaccine was well tolerated. SARS-CoV-specific antibody was detected by ELISA in 8 of 10 subjects and neutralizing antibody was detected in all subjects who received 3 doses of vaccine. SARS-CoV-specific CD4+ T-cell responses were detected in all vaccinees, and CD8+ T-cell responses in approximately 20% of individuals.

Conclusions: The VRC SARS DNA vaccine was well tolerated and produced cellular immune responses and neutralizing antibody in healthy adults.

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Figures

Fig. 1
Fig. 1
Magnitude and frequency of neutralizing antibody response. Individual subjects are designated by letters A–J, sorted by ascending age on the x-axis. The IC80 (inhibitory concentration 80%) reciprocal titer is represented on the y-axis. The time course of the study is shown for each subject: week 0 (yellow bars), week 8 (green bars), week 12 (blue bars), and week 32 (orange bars). Vaccinations were administered at weeks 0, 4, and 8. Subject “G” received 2 of 3 vaccinations.
Fig. 2
Fig. 2
Magnitude and frequency of CD4 and CD8 T-cell responses by ICS and ELISpot analysis at specific timepoints throughout the study. Magnitude of response is represented on the upper graph, percent positive CD4 (red bars) or CD8 cells (green bars) for ICS or spot-forming colonies (SFC) for ELISpot (blue bars). The horizontal black bars represent the mean. A sample was considered positive if it was above the thresholds indicated by the dashed lines. Separate positivity criteria for CD4 and CD8 ICS and ELISpot were developed and validated for overlapping peptide-based stimulations. The frequency of response is represented by percent responders on the lower graph. Weeks after enrollment is shown on the x-axis, applicable for upper and lower graphs. Vaccinations were administered at weeks 0, 4, and 8.
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