Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

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Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Vaccines ◽

10.3390/vaccines9040307 ◽

2021 ◽

Vol 9 (4) ◽

pp. 307

Author(s):

Yong Bok Seo ◽

You Suk Suh ◽

Ji In Ryu ◽

Hwanhee Jang ◽

Hanseul Oh ◽

...

Keyword(s):

T Cell ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Dependent Manner ◽

Viral Loads ◽

Cell Responses ◽

Rapid Spread

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

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Soluble Spike DNA vaccine provides long-term protective immunity against SAR-CoV-2 in mice and nonhuman primates

10.1101/2020.10.09.334136 ◽

2020 ◽

Author(s):

Yong Bok Seo ◽

You Suk Suh ◽

Ji In Ryu ◽

Hwanhee Jang ◽

Hanseul Oh ◽

...

Keyword(s):

T Cell ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Dependent Manner ◽

Viral Loads ◽

Cell Responses ◽

Rapid Spread

SummaryThe unprecedented and rapid spread of SARS-CoV-2 has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19 vaccinated nonhuman primate seroconverted rapidly and exhibited detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they did not develop fever and reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2 in human clinical trials.

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Correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the AV7909 anthrax vaccine candidate

Vaccine ◽

10.1016/j.vaccine.2017.07.076 ◽

2017 ◽

Vol 35 (37) ◽

pp. 4952-4959 ◽

Cited By ~ 12

Author(s):

Vladimir Savransky ◽

Jeffry D. Shearer ◽

Melicia R. Gainey ◽

Daniel C. Sanford ◽

Gloria S. Sivko ◽

...

Keyword(s):

Guinea Pigs ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Lethal Toxin ◽

Anthrax Lethal Toxin ◽

Anthrax Vaccine ◽

Antibody Levels

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A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model

Vaccines ◽

10.3390/vaccines9040340 ◽

2021 ◽

Vol 9 (4) ◽

pp. 340

Author(s):

Izabela K Ragan ◽

Lindsay M Hartson ◽

Taru S Dutt ◽

Andres Obregon-Henao ◽

Rachel M Maison ◽

...

Keyword(s):

Vaccine Candidate ◽

Rapid Development ◽

Neutralizing Antibody ◽

Emerging Diseases ◽

Effective Vaccine ◽

Preliminary Evaluation ◽

Sequencing Data ◽

Post Challenge ◽

Vaccine Candidates ◽

The Impact

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

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Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach

10.1101/2020.07.01.150805 ◽

2020 ◽

Author(s):

Rohit Pritam Das ◽

Manaswini Jagadeb ◽

Surya Narayan Rath

Keyword(s):

Global Health ◽

Viral Infection ◽

B Cell ◽

Molecular Interaction ◽

Vaccine Candidate ◽

Virus Disease ◽

Spike Protein ◽

Vaccine Candidates ◽

Mhc Molecules ◽

Peptide Candidate

Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19.

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Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response

10.1101/2020.06.27.175166 ◽

2020 ◽

Cited By ~ 1

Author(s):

Nanda Kishore Routhu ◽

Sailaja Gangadhara ◽

Narayanaiah Cheedarla ◽

Ayalnesh Shiferaw ◽

Sheikh Abdul Rahman ◽

...

Keyword(s):

Antibody Response ◽

Room Temperature ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Full Length ◽

Spike Protein ◽

Strongly Correlated ◽

Igg Antibodies ◽

Potential Vaccine

AbstractThere is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.

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First-in-Human Trial of a SARS CoV 2 Recombinant Spike Protein Nanoparticle Vaccine

10.1101/2020.08.05.20168435 ◽

2020 ◽

Cited By ~ 8

Author(s):

Cheryl Keech ◽

Gary Albert ◽

Patricia Reed ◽

Susan Neal ◽

Joyce S. Plested ◽

...

Keyword(s):

T Cell ◽

Adverse Events ◽

Immune Responses ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Healthy Adults ◽

Spike Protein ◽

Wild Type Virus ◽

Cell Responses ◽

The Mean

Background NVX-CoV2373 is a recombinant nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins. We present the Day 35 primary analysis of our trial of NVX-CoV2373 with or without the saponin-based Matrix-M1 adjuvant in healthy adults. Methods This is a randomized, observer-blinded, placebo-controlled, phase 1 trial in 131 healthy adults. Trial vaccination comprised two intramuscular injections, 21 days apart. Primary outcomes were reactogenicity, safety labs, and immunoglobulin G (IgG) anti-spike protein response. Secondary outcomes included adverse events, wild-type virus neutralizing antibody, and T-cell responses. Results Participants received NVX-CoV2373 with or without Matrix-M1 (n=106) or placebo (n=25). There were no serious adverse events. Reactogenicity was mainly mild in severity and of short duration (mean ≥ 2 days), with second vaccinations inducing greater local and systemic reactogenicity. The adjuvant significantly enhanced immune responses and was antigen dose-sparing, and the two-dose 5μg NVX-CoV2373/Matrix-M1 vaccine induced mean anti-spike IgG and neutralizing antibody responses that exceeded the mean responses in convalescent sera from COVID-19 patients with clinically significant illnesses. The vaccine also induced antigen-specific T cells with a largely T helper 1 (Th1) phenotype. Conclusions NVX-CoV2373/Matrix-M1 was well tolerated and elicited robust immune responses (IgG and neutralization) four-fold higher than the mean observed in COVID-19 convalescent serum from participants with clinical symptoms requiring medical care and induced CD4+ T-cell responses biased toward a Th1 phenotype. These findings suggest that the vaccine may confer protection and support transition to efficacy evaluations to test this hypothesis. (Funded by the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04368988).

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RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00402-5 ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Zezhong Liu ◽

Wei Xu ◽

Shuai Xia ◽

Chenjian Gu ◽

Xinling Wang ◽

...

Keyword(s):

Subunit Vaccine ◽

Vaccine Candidate ◽

High Titer ◽

Neutralizing Antibody ◽

Spike Protein ◽

Receptor Binding Domain ◽

Angiotensin Converting Enzyme 2 ◽

Specific Antibodies ◽

Good Potential ◽

Neutralizing Epitopes

AbstractThe pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy, thus calling for the development of safe and effective vaccines. The receptor-binding domain (RBD) in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG, as an immunopotentiator, elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections. The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus (SARSr-CoV). Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge. These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants, as well as future emerging SARSr-CoVs and re-emerging SARS-CoV.

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Global distribution of single amino acid polymorphisms in Plasmodium vivax Duffy-binding-like domain and implications for vaccine development efforts

Open Biology ◽

10.1098/rsob.200180 ◽

2020 ◽

Vol 10 (9) ◽

pp. 200180

Author(s):

Payal Mittal ◽

Siddhartha Mishra ◽

Sonalika Kar ◽

Veena Pande ◽

Abhinav Sinha ◽

...

Keyword(s):

Plasmodium Vivax ◽

Binding Sites ◽

Vaccine Development ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Single Amino Acid ◽

Vaccine Candidates ◽

Malaria Burden ◽

Single Amino Acid Polymorphisms ◽

Polymorphic Residue

Plasmodium vivax ( Pv ) malaria continues to be geographically widespread with approximately 15 million worldwide cases annually. Along with other proteins, Duffy-binding proteins (DBPs) are used by plasmodium for RBC invasion and the parasite-encoded receptor binding regions lie in their Duffy-binding-like (DBL) domains—thus making it a prime vaccine candidate. This study explores the sequence diversity in Pv DBL globally, with an emphasis on India as it remains a major contributor to the global Pv malaria burden. Based on 1358 Pv DBL protein sequences available in NCBI, we identified 140 polymorphic sites within 315 residues of Pv DBL. Alarmingly, country-wise mapping of SAAPs from field isolates revealed varied and distinct polymorphic profiles for different nations. We report here 31 polymorphic residue positions in the global SAAP profile, most of which map to the Pv DBL subdomain 2 ( α 1– α 6). A distinct clustering of SAAPs distal to the DARC-binding sites is indicative of immune evasive strategies by the parasite. Analyses of Pv DBL-neutralizing antibody complexes revealed that between 24% and 54% of interface residues are polymorphic. This work provides a framework to recce and expand the polymorphic space coverage in Pv DBLs as this has direct implications for vaccine development studies. It also emphasizes the significance of surveying global SAAP distributions before or alongside the identification of vaccine candidates.

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