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

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, MSC-2610, Bethesda, MD 20892-3017, USA.
Vaccine (Impact Factor: 3.62). 10/2008; 26(50):6338-43. DOI: 10.1016/j.vaccine.2008.09.026
Source: PubMed


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

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    • "This system has been successfully employed in the study of highly pathogenic viruses including the influenza virus [33] and SARS-CoV [34], [35], [36]. Neutralizing antibody titers measured using pseudotyped SARS-CoV correlated well with the use of replication competent SARS-CoV [37], as such, this system has been widely used in the evaluation of SARS-CoV neutralizing antibodies [30], [38], [39], [40], [41]. In this study, the S-pps expressing human SARS-CoV S or RBD-modified chimeric S of civet SARS-CoV SZ3 strain and bat SL-CoV Rp3 and Rf1 strains were able to infect and enter CHO-ACE2 cells at similar extent (Figure S1A in File S1). "
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    • "Assessment of neutralizing activity in preclinical or clinical samples has been primarily by traditional plaque reduction neutralization (PRNT) or microneutralization (Anderson et al., 1985). PRNT suffers from limited sensitivity and nonspecificity, and is prone to technician error, is tedious, labor-intensive, and is not as reproducible as newer reporter pseudovirus methods developed for other viral diseases (Mascola et al., 2002; Pierson et al., 2006; Martin et al., 2008). Additionally the PRNT assay is time-consuming and not easily adapted to high throughput technology. "
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    • "This unformulated DNA vaccine appears to induce a similar level of immune responses to those observed in vaccinated horses protected from WNV. In addition, a recent clinical trial by these same NIH researchers tested an optimized but unformulated DNA vaccine for SARS coronavirus and demonstrated neutralizing antibodies in all subjects who received three doses of the vaccine [18]. "
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