DNA vaccine protection against SARS-CoV-2 in rhesus macaques

By Jingyou Yu, Lisa H. Tostanoski, Lauren Peter, N. Mercado, K. McMahan, S. Mahrokhian, Joseph P. Nkolola, Jinyan Liu, Zhenfeng Li, A. Chandrashekar and 44 more. 2020

1,010 citations recorded by the source corpus.

Prototype DNA vaccines for SARS-CoV-2 The development of a vaccine to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent biomedical need. Yu et al. designed a series of prototype DNA vaccines against the SARS-CoV-2 spike protein, which is used by the virus to bind and invade human cells. Analysis of the vaccine candidates in rhesus macaques showed that animals developed protective humoral and cellular immune responses when challenged with the virus. Neutralizing antibody titers were also observed at levels similar to those seen in humans who have recovered from SARS-CoV-2 infection. Science, this issue p. 806 Successful protection against SARS-CoV-2 in rhesus macaques by means of a prototype DNA vaccine is described. The global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers at levels comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. After vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with viral loads in sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.

Subfields: Immunology, Infectious Diseases

How researchers see this paper

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

In Immunology

1. Alessandro Sette
2. Bjoern Peters
3. Shane Crotty
4. F. Krammer
5. Morten Nielsen
6. Ole Lund

In Infectious Diseases

1. D. Veesler
2. A. Walls
3. F. Krammer
4. Alessandro Sette
5. Shane Crotty
6. Neeltje van Doremalen
7. Ralph S. Baric

Citations in the corpus

• Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “1368 Cell 183, 1367–1382, November 25, 2020 vectored vaccine platforms enabled rapid entry into the clinic with vaccines encoding SARS-CoV-2 S antigens (Folegatti et al., 2020; Jackson et al., 2020; Mulligan et al., 2020; Sahin et al., 2020; Yu et al., 2020; Zhu et al., 2020a).”
• Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial (2020, result): “16 Although a correlate of protection has not been defined for COVID-19, high levels of neutralising antibodies have been shown in convalescent individuals, with a wide range, as confirmed in our study.”
• Mechanisms of SARS-CoV-2 Transmission and Pathogenesis (2020, neutral): “, IFN- γ) responses did not correlate with immune protection from DNA vaccines with different components of the SARS-CoV-2 Spike protein [126,134].”
• SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma (2021, neutral): “While antibody effector functions elicited by infection and vaccination have been implicated in protecting from reinfection and disease 35,36 , the role of non-neutralizing antibodies and the efficacy of T cell responses to 501Y.V2 remain to be elucidated.”
• Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, neutral): “Furthermore, candidate vaccines that include only RBD antigens lack the ability to induce NTDreactive neutralizing antibodies (Laczko et al., 2020; Mulligan et al., 2020; Smith et al., 2020; Yu et al., 2020).”
• Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection (2021, background): “The presence of substerilizing neutralizing antibody titers at the time of SARS-CoV-2 exposure would blunt the size of the initial infection, and may provide an added contribution to limiting COVID-19 severity, on the basis of observations of protective immunity for other human respiratory viral inf”
• COVID-19 neutralizing antibodies predict disease severity and survival (2020, neutral): “Similarly, animal models testing candidate vaccine approaches have demonstrated that protection against SARS-CoV-2 challenge is positively correlated with the development of high titers of neutralizing antibodies (Mercado et al., 2020; Yu et al., 2020).”