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1.
Vaccine ; 40(21): 2960-2969, 2022 05 09.
Article in English | MEDLINE | ID: covidwho-1773836

ABSTRACT

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of T cells and antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.


Subject(s)
COVID-19 , Vaccines, DNA , Viral Vaccines , Animals , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Macaca mulatta , Mice , Mice, Inbred BALB C , SARS-CoV-2 , Vaccination
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321794

ABSTRACT

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the outbreak of viral pneumonia disease, COVID-19 which first emerged in mid-December 2019 in the city of Wuhan in central China. As of February 25, 2020 there are 80,994 people infected and 2,760 deaths, and documented human-to-human transmission across multiple continents. At this time, no vaccine is available to control further dissemination of the disease. We have previously developed a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein that was deployed in response to the MERS outbreak in South Korea. This vaccine induced potent antibody and CTL responses, and provided protection in a NHP challenge model. In the clinic, the vaccine generated humoral immunity including neutralizing antibody responses, as well as T cell immunity. Here we build on this prior work and report on the rapid development of a synthetic DNA-based vaccine targeting the major surface antigen Spike protein of SARS-CoV-2. The engineered construct, INO-4800 induced robust expression of the Spike protein in vitro, and generated antibody and T cell responses following a single immunization in mice and guinea pigs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further study for mobilization against this emerging disease threat.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311378

ABSTRACT

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we evaluate the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induces both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 x 10 6 pfu) via the intranasal and intratracheal routes we observe significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 is associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provides no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.

4.
Cell Rep ; 38(5): 110318, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1654152

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Nanoparticles/administration & dosage , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Binding Sites , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/genetics , Cricetinae , Epitopes , Guinea Pigs , Immunogenicity, Vaccine , Mice , Nanoparticles/chemistry , Nucleic Acid-Based Vaccines/administration & dosage , Nucleic Acid-Based Vaccines/chemistry , Nucleic Acid-Based Vaccines/genetics , Nucleic Acid-Based Vaccines/immunology , Polysaccharides/chemistry , Polysaccharides/genetics , Polysaccharides/immunology , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccine Potency
5.
Open Forum Infectious Diseases ; 8(Supplement_1):S391-S392, 2021.
Article in English | PMC | ID: covidwho-1570006

ABSTRACT

First generation COVID-19 vaccines matched to the original Wuhan-Hu-1 (WT) strain are showing reduced efficacy against emerging SARS-CoV-2 variants of concern (VOC). In response, next generation vaccines either matched to a single variant or designed to provide broader coverage across the VOC group are being developed. The latter pan-SARS-CoV-2 approach may offer substantial advantages in terms of cross-strain protection, immune coverage, reduced susceptibility to escape mutants, and non-restricted geographical use. Here we have employed our SynCon® design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants. Compared to WT and VOC-matched vaccines which showed limited cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster vaccination model showed enhanced humoral responses against VOCs in a heterologous pWT prime/INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOCs as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT-matched vaccines.Competing Interest StatementC.C.R., V.M.A., R.K., K.S., J.T., B.S., D.E., J.W., I.M., A.D., Z.E., P.P., D.A. M.Y., J.F., R.F., M.V., J.J.K., L.M.H., S.J.R., T.R.F.S., K.E.B. are employees of Inovio Pharmaceuticals and as such receive salary and benefits, including ownership of stock and stock options, from the company. D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board services. Remuneration received by D.B.W. includes direct payments or stock or stock options, and in the interest of disclosure he notes potential conflicts associated with this work with Inovio and possibly others. In addition, he has a patent DNA vaccine delivery pending to Inovio. All other authors report there are no competing interests.

8.
Open forum infectious diseases ; 8(Suppl 1):387-388, 2021.
Article in English | EuropePMC | ID: covidwho-1564905

ABSTRACT

Background DNA vaccines are safe, tolerable, elicit humoral and cellular responses, allow for repeated dosing over time, are thermostable at room temperature, and are easy to manufacture. We present a compilation of Phase 1 and Phase 2 data of Inovio’s US COVID-19 DNA Vaccine (INO-4800) targeting the full-length Spike antigen of SARS-CoV-2. A South Korean Phase 2 study is ongoing. Methods Participants in the open-label Phase 1 trial received 0.5 mg, 1.0 mg or 2.0 mg intradermally (ID) followed by electroporation (EP) at Days 0 and 28. An optional booster dose was administered >6 months post-dose 2. The Phase 2 further compared the 1.0 mg and 2.0 mg doses against placebo in a total of 401 participants randomized at a 3:3:1:1 ratio. ClinicalTrials.gov identifiers: NCT04336410 and NCT04642638 Results The majority of adverse events (AEs) related to INO-4800 across both trials were mild in severity and did not increase in frequency with age and subsequent doses. In Phase 1, 78% (14/18) and 84% (16/19) of subjects generated neutralizing antibody responses with geometric mean titers (GMTs) of 17.4 (95%CI 8.3, 36.5) and 62.3 (95% CI 36.4, 106.7) in the 1.0 and 2.0 groups, respectively (Figure 1). By week 8, 74% (14/19) and 100% (19/19) subjects generated T cell responses by Th1- associated IFNγ ELISPOT assay . Following a booster dose, neutralizing GMTs rose to 82.2 (95% CI 38.2, 176.9) and 124.7 (95% CI 62.8, 247.7) in the 1.0 mg and 2.0 mg groups, respectively, demonstrating the ability of INO-4800 to boost (Figure 2). In Phase 2, neutralizing antibody responses demonstrated GMTs of 93.6 (95%CI 77.3, 113.4) in the 1.0 mg dose group and 150.6 (95%CI 123.8, 183.1) in the 2.0 mg dose group (Figure 3). Conclusion INO-4800 appears safe and tolerable as a primary series and as a booster with the induction of both humoral and cellular immune responses. In addition to eliciting neutralizing antibodies, INO-4800 also induced T cell immune responses as demonstrated by IFNγ ELISpot. Finally, as a homologous booster, INO-4800, when administered 6-10.5 months following the primary series, resulted in an increased immune response without increase in reactogenicity. The 2.0 mg dose was selected for Phase 3 evaluation. Disclosures Joseph Agnes, PhD, Inovio (Employee, Shareholder) Mary Giffear, BS, Inovio Pharmaceuticals, Inc. (Employee) Kimberly A. Kraynyak, PhD, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, Stock options) Dinah Amante, BS, Inovio (Employee) Emma Reuschel, PhD, Inovio Pharmaceuticals (Employee) Aaron Christensen-Quick, PhD, Inovio Pharmaceuticals, Inc (Employee) Viviane M. Andrade, PhD, Inovio Pharmaceuticals Inc. (Employee) Gabriella Garufi, PhD, Inovio Pharmaceuticals, Inc. (Employee) Albert Sylvester, MS, Inovio (Employee, Shareholder) Matthew P. Morrow, PhD, Inovio Pharmaceuticals (Employee) Patrick P. Pezzoli, BS, Inovio Pharmaceuticals, Inc. (Employee) Jan Pawlicki, PhD, Inovio Pharmaceuticals (Employee) Elisabeth Gillespie, PhD, Inovio Pharmaceuticals, Inc. (Employee) Katherine Schultheis, MSc, Inovio Pharmaceuticals (Employee) Hedieh Badie, PhD, INOVIO Pharmaceuticals (Employee) Timothy A. Herring, MPH, Inovio Pharmaceuticals, Inc. (Employee, Other Financial or Material Support, Own stock in the company) Keiko O. Simon, PhD, Inovio Pharmaceuticals (Employee) Trevor R. F. Smith, PhD, Inovio (Employee, Shareholder) Stephanie Ramos, PhD, Inovio Pharmaceuticals (Employee) Jessica Lee, MPH, Inovio Pharmaceuticals (Employee) Michael Dallas, PhD, Inovio Pharmaceuticals, Inc. (Employee, Shareholder) Ami Shah Brown, PhD, Abbot Laboratories (Shareholder)IBB Biotech ETF (Shareholder)Inovio Pharmaceuticals (Employee)J & J (Shareholder)Moderna (Shareholder) Jacqueline E. Shea, PhD, Inovio Pharmaceuticals (Employee, Shareholder) J Joseph Kim, PhD, Inovio (Employee) David Weiner, PhD, Inovio (Board Member, Grant/Research Support, Shareholder, I serve on the SAB in addition to the above activities) Kate Broderick, PhD, Inovio (Employee) Trevor Mc ullan, MSc, Inovio (Shareholder) Jean Boyer, PhD, Inovio (Employee) Laurent Humeau, PhD, Inovio Pharmaceuticals (Employee) Mammen P. Mammen Jr., MD, Inovio Pharmaceuticals (Employee)

9.
Open forum infectious diseases ; 8(Suppl 1):S391-S392, 2021.
Article in English | EuropePMC | ID: covidwho-1564784

ABSTRACT

Background First-generation COVID-19 vaccines are matched to spike protein of the Wuhan-H1 (WT) strain. Convalescent and vaccinee samples show reduced neutralization of SARS-CoV-2 variants of concern (VOC). Next generation DNA vaccines could be matched to single variants or synthetically designed for broader coverage of multiple VOCs. Methods The synthetic consensus (SynCon®) sequence for INO-4802 SARS-CoV-2 spike with focused RBD changes and dual proline mutations was codon-optimized (Figure 1). Sequences for wild-type (pWT) and B.1.351 (pB.1.351) were similarly optimized. Immunogenicity was evaluated in BALB/c mice. Pre-clinical efficacy was assessed in the Syrian Hamster model. Figure 1. Design Strategy for INO-4802 Results INO-4802 induced potent neutralizing antibody responses against WT, B.1.1.7, P.1, and B.1.351 VOC in a murine model. pWT vaccinated animals showed a 3-fold reduction in mean neutralizing ID50 for the B.1.351 pseudotyped virus. INO-4802 immunized animals had significantly higher (p = 0.0408) neutralizing capacity (mean ID50 816.16). ID50 of pB.1.351 serum was reduced 7-fold for B.1.1.7 and significantly lower (p = 0.0068) than INO-4802 (317.44). INO-4802 neutralized WT (548.28) comparable to pWT. INO-4802 also neutralized P.1 (1026.6) (Figure 2). pWT, pB.1.351 or INO-4802 induced similar T-cell responses against all variants. INO-4802 skewed towards a TH1-response. All hamsters vaccinated with INO-4802 or pB.1.351 were protected from weight loss after B.1.351 live virus challenge. 4/6 pWT immunized hamsters were completely protected. pWT immunized hamsters neutralized WT (1090) but not B.1.351 (39.16). INO-4802 neutralized both WT (672.2) and B.1.351 (1121) (Figure 3). We observed higher increase of binding titers following heterologous boost with INO-4802 (3.6 – 4.4 log2-fold change) than homologous boost with pWT (2.0 – 2.4 log2 fold change) (Figure 4). Figure 2. INO-4802 Induces Functional Humoral Immune Response Against SARS-CoV-2 Variants of Concern Figure 3. INO-4802 Protects Hamsters Against Challenge With B.1.351 Live Virus Figure 4. Heterologous Boost with INO-4802 Induces Humoral Immune Response Against SARS-CoV-2 Variants Conclusion Vaccines matching single VOCs, like pB.1.351 and pWT, elicit responses against the matched antigen but have reduced cross-reactivity. Presenting a pan-SARS-CoV-2 approach, INO-4802 may offer substantial advantages in terms of cross-strain protection, reduced susceptibility to escape mutants and non-restricted geographical use. Disclosures Katherine Schultheis, MSc, Inovio Pharmaceuticals (Employee) Charles C. Reed, PhD, Inovio Pharmaceuticals (Employee, Shareholder) Viviane M. Andrade, PhD, Inovio Pharmaceuticals Inc. (Employee) Richa Kalia, MS, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, I have stock options with Inovio Pharmaceuticals as an employee.) Jared Tur, PhD, Inovio (Employee) Blake Schouest, PhD, Inovio Pharmaceuticals (Employee) Dustin Elwood, PhD, Inovio Pharmaceuticals (Employee) Arthur Doan, n/a, Inovio (Employee) Patrick Pezzoli, BS, Inovio (Employee) Dinah Amante, BS, Inovio (Employee) David Weiner, PhD, Inovio (Board Member, Grant/Research Support, Shareholder, I serve on the SAB in addition to the above activities) J Joseph Kim, PhD, Inovio (Employee) Laurent Humeau, PhD, Inovio Pharmaceuticals (Employee) Stephanie Ramos, PhD, Inovio Pharmaceuticals (Employee) Trevor R. F. Smith, PhD, Inovio (Employee, Shareholder) Kate Broderick, PhD, Inovio (Employee).

10.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295818

ABSTRACT

Here we have employed SynCon ® design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants of concern (VOC). Compared to WT and VOC-matched vaccines which showed reduced cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster challenge model demonstrated that INO-4802 conferred superior protection following intranasal B.1.351 challenge. Protection against weight loss associated with WT, B.1.1.7, P.1 and B.1.617.2 challenge was also demonstrated. Vaccinated hamsters showed enhanced humoral responses against VOC in a heterologous WT vaccine prime and INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOC as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT-matched vaccines.

11.
NPJ Vaccines ; 6(1): 121, 2021 Oct 14.
Article in English | MEDLINE | ID: covidwho-1469970

ABSTRACT

Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with broadened host specificity, pathogenicity, and immune evasion to vaccine-induced immunity. Here we compared humoral and cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested.

12.
Cell Rep Med ; 2(10): 100420, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1450242

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health and social and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (i.d.)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800, currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and induced spike antigen and RBD binding antibodies with ADCP and ADCD activity. Sera from the animals neutralized both the D614 and G614 SARS-CoV-2 pseudotype viruses. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T cell and neutralizing antibody responses. These responses were associated with lower viral loads in the lung. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system, which are likely important for providing durable protection against COVID-19 disease.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Lung/virology , T-Lymphocytes/immunology , Animals , Antibodies, Neutralizing/blood , COVID-19 Vaccines/therapeutic use , Female , Injections, Intradermal , Macaca mulatta , Male , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/therapeutic use , Viral Load
13.
Vaccine ; 39(34): 4885-4894, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1284599

ABSTRACT

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 × 106 pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.


Subject(s)
COVID-19 , Vaccines, DNA , Viral Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , Macaca mulatta , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
14.
EClinicalMedicine ; 31: 100689, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-987565

ABSTRACT

BACKGROUND: A vaccine against SARS-CoV-2 is of high urgency. Here the safety and immunogenicity induced by a DNA vaccine (INO-4800) targeting the full length spike antigen of SARS-CoV-2 are described. METHODS: INO-4800 was evaluated in two groups of 20 participants, receiving either 1.0 mg or 2.0 mg of vaccine intradermally followed by CELLECTRA® EP at 0 and 4 weeks. Thirty-nine subjects completed both doses; one subject in the 2.0 mg group discontinued trial participation prior to receiving the second dose. ClinicalTrials.gov identifier: NCT04336410. FINDINGS: The median age was 34.5, 55% (22/40) were men and 82.5% (33/40) white. Through week 8, only 6 related Grade 1 adverse events in 5 subjects were observed. None of these increased in frequency with the second administration. No serious adverse events were reported. All 38 subjects evaluable for immunogenicity had cellular and/or humoral immune responses following the second dose of INO-4800. By week 6, 95% (36/38) of the participants seroconverted based on their responses by generating binding (ELISA) and/or neutralizing antibodies (PRNT IC50), with responder geometric mean binding antibody titers of 655.5 [95% CI (255.6, 1681.0)] and 994.2 [95% CI (395.3, 2500.3)] in the 1.0 mg and 2.0 mg groups, respectively. For neutralizing antibody, 78% (14/18) and 84% (16/19) generated a response with corresponding geometric mean titers of 102.3 [95% CI (37.4, 280.3)] and 63.5 [95% CI (39.6, 101.8)], in the respective groups. By week 8, 74% (14/19) and 100% (19/19) of subjects generated T cell responses by IFN-É£ ELISpot assay with the median SFU per 106 PBMC of 46 [95% CI (21.1, 142.2)] and 71 [95% CI (32.2, 194.4)] in the 1.0 mg and 2.0 mg groups, respectively. Flow cytometry demonstrated a T cell response, dominated by CD8+ T cells co-producing IFN-É£ and TNF-α, without increase in IL-4. INTERPRETATION: INO-4800 demonstrated excellent safety and tolerability and was immunogenic in 100% (38/38) of the vaccinated subjects by eliciting either or both humoral or cellular immune responses. FUNDING: Coalition for Epidemic Preparedness Innovations (CEPI).

15.
J Clin Microbiol ; 58(11)2020 10 21.
Article in English | MEDLINE | ID: covidwho-733184

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of COVID-19, resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >20 million people worldwide, with >5 million cases in the United States (11 August 2020). The development of diagnostic and research tools to determine infection and vaccine efficacy is critically needed. We have developed multiple serologic assays using newly designed SARS-CoV-2 reagents for detecting the presence of receptor-binding antibodies in sera. The first assay is surface plasmon resonance (SPR) based and can quantitate both antibody binding to the SARS-CoV-2 spike protein and blocking to the Angiotensin-converting enzyme 2 (ACE2) receptor in a single experiment. The second assay is enzyme-linked immunosorbent assay (ELISA) based and can measure competition and blocking of the ACE2 receptor to the SARS-CoV-2 spike protein with antispike antibodies. The assay is highly versatile, and we demonstrate the broad utility of the assay by measuring antibody functionality of sera from small animals and nonhuman primates immunized with an experimental SARS-CoV-2 vaccine. In addition, we employ the assay to measure receptor blocking of sera from SARS-CoV-2-infected patients. The assay is shown to correlate with pseudovirus neutralization titers. This type of rapid, surrogate neutralization diagnostic can be employed widely to help study SARS-CoV-2 infection and assess the efficacy of vaccines.


Subject(s)
Antibodies, Blocking/blood , Betacoronavirus/immunology , Clinical Laboratory Techniques , Coronavirus Infections/diagnosis , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/diagnosis , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/isolation & purification , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Coronavirus Infections/blood , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Enzyme-Linked Immunosorbent Assay , Guinea Pigs , Humans , Immunoglobulin G/blood , Mice , Neutralization Tests , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , Primates , Rabbits , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Surface Plasmon Resonance , Viral Vaccines/administration & dosage , Viral Vaccines/immunology
16.
Nat Commun ; 11(1): 2601, 2020 05 20.
Article in English | MEDLINE | ID: covidwho-326048

ABSTRACT

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.


Subject(s)
Antigens, Viral/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/immunology , Viral Vaccines/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/immunology , Antigens, Viral/chemistry , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Epitope Mapping , Guinea Pigs , Immunity, Humoral , Immunoglobulin G/immunology , Lung/immunology , Mice , Mice, Inbred BALB C , Middle East Respiratory Syndrome Coronavirus , Models, Animal , Peptidyl-Dipeptidase A/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Viral Vaccines/chemistry
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