A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice

By Zhi-yong Yang, W. Kong, Yue Huang, A. Roberts, B. Murphy, K. Subbarao, G. Nabel. Nature, 2004

678 citations recorded by the source corpus.

Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/7be09cacee1583543e1392f248892cd9461ea2dc

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Animal Science and Zoology

In Infectious Diseases

Citations in the corpus

Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response (2011, background): “Thus, the humoral immune response critically contributes to immune control of SARS-CoV infection (9, 26, 47, 66), and a delayed or diminished control of SARS-CoV by antibodies due to TMPRSS2 might contribute to disease progression.”
SARS-CoV-2 infection protects against rechallenge in rhesus macaques (2020, methodology): “2A) and neutralizing antibody (NAb) responses using both a pseudovirus neutralization assay (10) (Fig.”
From SARS to MERS, Thrusting Coronaviruses into the Spotlight (2019, background): “Other studies in a mouse model structured a DNA vaccine encoding the full-length S protein of the SARS-CoV Urbani strain that not only induced T-cell and neutralizing-antibody responses, but also stimulated protective immunity [81].”
Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19) (2020, background): “DNA Vaccine DNA vaccines represent an innovative approach by direct injection of plasmids encoding the antigens, accompanied with a wide range of immune responses [76].”
Coronavirus Pathogenesis and the Emerging Pathogen Severe Acute Respiratory Syndrome Coronavirus (2005, background): “(350) demonstrated that a DNA vaccine encoding the codon-”
First infection by all four non-severe acute respiratory syndrome human coronaviruses takes place during childhood (2013, methodology): “Artificially synthesised S fragments of HCoV-OC43, -229E, -HKU1, and -NL63 were cloned into the eukaryotic expression plasmid pVRC (a gift from Dr. Gary Nabel, NIH, USA) and named pVRC-229E-S, -OC43-S, -HKU1-S, and -NL63-S, respectively (Figure 1A).”
Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies (2020, background): “We focused specifically on the S and N proteins as these are known to induce potent and long-lived immune responses in SARS-CoV (Channappanavar et al., 2014; Deming et al., 2006; Graham et al., 2012; W. J. Liu et al., 2017; X Liu et al., 2004; J. Wang et al., 2003; Yang et al., 2004).”
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response (2020, positive): “Another study shown that this strategy was effective to elicit protective immunity producing neutralizing antibodies in mice [46, 47] .”
Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. (2019, background): “replication in susceptible hosts, including mice, ferrets, hamsters, and macaques (24, 34, 35).”