scholarly journals Multivalent nanoparticle-based vaccines protect hamsters against SARS-CoV-2 after a single immunization

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shiho Chiba ◽  
Steven J. Frey ◽  
Peter J. Halfmann ◽  
Makoto Kuroda ◽  
Tadashi Maemura ◽  
...  
Keyword(s):  
Coat Protein ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Vaccine Platform ◽  
Death Rates ◽  
Widespread Distribution ◽  
Syrian Hamsters ◽  
Vaccine Trials ◽  
Multiple Copies ◽  
Antibody Titers

AbstractThe COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.

scholarly journals Multivalent Nanoparticle-Based Vaccines Protect Hamsters Against SARS-CoV-2 After a Single Immunization

2020 ◽  
Author(s):  
Shiho Chiba ◽  
Steven J. Frey ◽  
Peter J. Halfmann ◽  
Makoto Kuroda ◽  
Tadashi Maemura ◽  
...  
Keyword(s):  
Coat Protein ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Vaccine Platform ◽  
Death Rates ◽  
Widespread Distribution ◽  
Syrian Hamsters ◽  
Vaccine Trials ◽  
Multiple Copies ◽  
Antibody Titers

Abstract The COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage1,2 and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters3 from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.

scholarly journals ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Robert J. Fischer ◽  
Neeltje van Doremalen ◽  
Danielle R. Adney ◽  
Claude Kwe Yinda ◽  
Julia R. Port ◽  
...  
Keyword(s):  
Single Dose ◽  
Vaccine Efficacy ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Subgenomic Rna ◽  
Syrian Hamsters ◽  
Fold Reduction ◽  
Histopathological Evaluation ◽  
Gross Lesions ◽  
Pulmonary Pathology

AbstractWe investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observe a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 do not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals do not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus can be detected in lungs of vaccinated animals. Histopathological evaluation shows extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.

scholarly journals Ad26.COV2.S-elicited immunity protects against G614 spike variant SARS-CoV-2 infection in Syrian hamsters and does not enhance respiratory disease in challenged animals with breakthrough infection after sub-optimal vaccine dosing

2021 ◽  
Author(s):  
Joan E.M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Disease ◽  
Syrian Hamster ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Upper Respiratory Tract ◽  
Breakthrough Infection ◽  
Syrian Hamsters ◽  
Antibody Titers ◽  
Upper Respiratory

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1x109 vp and 1x1010 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

scholarly journals Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Joan E. M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Respiratory Disease ◽  
Syrian Hamster ◽  
Neutralizing Antibodies ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Upper Respiratory Tract ◽  
Syrian Hamsters ◽  
Antibody Titers ◽  
Upper Respiratory

AbstractPreviously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

scholarly journals Immunogenicity of an AAV-based, room-temperature stable, single dose COVID-19 vaccine in mice and non-human primates

2021 ◽  
Author(s):  
Nerea Zabaleta ◽  
Wenlong Dai ◽  
Urja Bhatt ◽  
Jessica A Chichester ◽  
Reynette Estelien ◽  
...  
Keyword(s):  
Single Dose ◽  
Room Temperature ◽  
Neutralizing Antibody ◽  
Global Scale ◽  
Emerging Pathogens ◽  
Vaccine Platform ◽  
Population Immunity ◽  
Antibody Titers ◽  
High Yields ◽  
Effective Immunization

SummaryThe SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 million deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological and logistical attributes of the vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity in mouse and nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained at 5 months and are complemented by functional memory T-cells responses. The AAVrh32.33 capsid of the AAVCOVID vaccine is an engineered AAV to which no relevant pre-existing immunity exists in humans. Moreover, the vaccine is stable at room temperature for at least one month and is produced at high yields using established commercial manufacturing processes in the gene therapy industry. Thus, this methodology holds as a very promising single dose, thermostable vaccine platform well-suited to address emerging pathogens on a global scale.

scholarly journals Treatment-Emergent Influenza Variant Viruses With Reduced Baloxavir Susceptibility: Impact on Clinical and Virologic Outcomes in Uncomplicated Influenza

2019 ◽  
Author(s):  
Takeki Uehara ◽  
Frederick G Hayden ◽  
Keiko Kawaguchi ◽  
Shinya Omoto ◽  
Aeron C Hurt ◽  
...  
Keyword(s):  
Infectious Virus ◽  
Virus Titer ◽  
Virus Detection ◽  
Neutralizing Antibody ◽  
Careful Study ◽  
Clinical Trial Registration ◽  
In Vitro Susceptibility ◽  
Antibody Titers ◽  
Virus Emergence

Abstract Background Single-dose baloxavir rapidly reduces influenza virus titers and symptoms in patients with uncomplicated influenza, but viruses with reduced in vitro susceptibility due to amino acid substitutions at position 38 of polymerase acidic protein (PA/I38X) sometimes emerge. Methods We evaluated the kinetics, risk factors, and effects on clinical and virologic outcomes of emergence of PA/I38X-substituted viruses. Results Viruses containing PA/I38X substitutions were identified 3–9 days after baloxavir treatment in 9.7% (36/370) of patients, of whom 85.3% had transient virus titer rises. Median time to sustained cessation of infectious virus detection was 192, 48, and 96 hours in the baloxavir recipients with PA/I38X-substituted viruses, without PA/I38X-substituted viruses, and placebo recipients, respectively. The corresponding median times to alleviation of symptoms were 63.1, 51.0, and 80.2 hours, respectively. After day 5, symptom increases occurred in 11.5%, 8.0%, and 13.0%, respectively, and in 8.9% of oseltamivir recipients. Variant virus emergence was associated with lower baseline neutralizing antibody titers. Conclusions The emergence of viruses with PA/I38X substitutions following baloxavir treatment was associated with transient rises in infectious virus titers, prolongation of virus detectability, initial delay in symptom alleviation, and uncommonly with symptom rebound. The potential transmissibility of PA/I38X-substituted viruses requires careful study. Clinical Trial Registration NCT02954354.

scholarly journals A measles-vectored COVID-19 vaccine induces long-term immunity and protection from SARS-CoV-2 challenge in mice

2021 ◽  
Author(s):  
Phanramphoei N. Frantz ◽  
Aleksandr Barinov ◽  
Claude Ruffié ◽  
Chantal Combredet ◽  
Valérie Najburg ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Measles Virus ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Full Length ◽  
World Population ◽  
Boost Immunization ◽  
Antibody Titers ◽  
Vectored Vaccine

AbstractIn light of the expanding SARS-CoV-2 pandemic, developing efficient vaccines that can provide sufficient coverage for the world population is a global health priority. The measles virus (MV)-vectored vaccine is an attractive candidate given the measles vaccine’s extensive safety history, well-established manufacturing process, and induction of strong, long-lasting immunity. We developed an MV-based SARS-CoV-2 vaccine using either the full-length spike (S) or S2 subunit as the antigen. While the S2 antigen failed to induce neutralizing antibodies, the prefusion-stabilized, full-length S (MV-ATU2-SF-2P-dER) construct proved to be an attractive vaccine candidate, eliciting strong Th1-dominant T-cell and neutralizing antibody responses against the S antigen while minimizing reactivity to the vector itself. Neutralizing antibody titers remained high three months after homologous prime-boost immunization, and infectious virus was undetectable in all animals after challenge with a mouse-adapted SARS-CoV-2 virus.

Presence of antibody in virus-infected brain cells of SSPE ferrets

1983 ◽  
Vol 41 ◽  
pp. 804-805
Author(s):  
Hannah R. Brown ◽  
Tammy L. Donato ◽  
Halldor Thormar
Keyword(s):  
Measles Virus ◽  
Plasma Cells ◽  
Subacute Sclerosing Panencephalitis ◽  
Protein A ◽  
Neutralizing Antibody ◽  
Brain Cells ◽  
Antibody Titers ◽  
A Cell ◽  
The Central Nervous System ◽  
The Brain

Measles virus specific immunoglobulin G (IgG) has been found in the brains of patients with subacute sclerosing panencephalitis (SSPE), a slowly progressing disease of the central nervous system (CNS) in children. IgG/albumin ratios indicate that the antibodies are synthesized within the CNS. Using the ferret as an animal model to study the disease, we have been attempting to localize the Ig's in the brains of animals inoculated with a cell associated strain of SSPE. In an earlier report, preliminary results using Protein A conjugated to horseradish peroxidase (PrAPx) (Dynatech Diagnostics Inc., South Windham, ME.) to detect antibodies revealed the presence of immunoglobulin mainly in antibody-producing plasma cells in inflammatory lesions and not in infected brain cells.In the present experiment we studied the brain of an SSPE ferret with neutralizing antibody titers of 1:1024 in serum and 1:512 in CSF at time of sacrifice 7 months after i.c. inoculation with SSPE measles virus-infected cells. The animal was perfused with saline and portions of the brain and spinal cord were immersed in periodate-lysine-paraformaldehyde (P-L-P) fixative. The ferret was not perfused with fixative because parts of the brain were used for virus isolation.

scholarly journals Convalescent Plasma Efficacy in Life-Threatening COVID-19 Patients Admitted to the ICU: A Retrospective Cohort Study

2021 ◽  
Vol 10 (10) ◽  
pp. 2113
Author(s):  
Mohamed Abuzakouk ◽  
Khaled Saleh ◽  
Manuel Algora ◽  
Ahmad Nusair ◽  
Jawahir Alameri ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Clinical Improvement ◽  
Primary Outcome ◽  
Neutralizing Antibody ◽  
Limited Data ◽  
Inverse Probability Weights ◽  
Single Center Study ◽  
Life Threatening ◽  
Antibody Titers ◽  
Disease Severity Scale

(1) Background: There are limited data regarding the efficacy of convalescent plasma (CP) in critically ill patients admitted to the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). We aimed to determine whether CP is associated with better clinical outcome among these patients. (2) Methods: A retrospective single-center study including adult patients with laboratory-confirmed SARS-CoV-2 infection admitted to the ICU for acute respiratory failure. The primary outcome was time to clinical improvement, within 28 days, defined as patient discharged alive or reduction of 2 points on a 6-point disease severity scale. (3) Results: Overall, 110 COVID-19 patients were admitted. Thirty-two patients (29%) received CP; among them, 62.5% received at least one CP with high neutralizing antibody titers (≥1:160). Clinical improvement occurred within 28 days in 14 patients (43.7%) of the CP group vs. 48 patients (61.5%) in the non-CP group (hazard ratio (HR): 0.75 (95% CI: 0.41–1.37), p = 0.35). After adjusting for potential confounding factors, CP was not independently associated with time to clinical improvement (HR: 0.53 (95% CI: 0.23–1.22), p = 0.14). Additionally, the average treatment effects of CP, calculated using the inverse probability weights (IPW), was not associated with the primary outcome (−0.14 days (95% CI: −3.19–2.91 days), p = 0.93). Hospital mortality did not differ between CP and non-CP groups (31.2% vs. 19.2%, p = 0.17, respectively). Comparing CP with high neutralizing antibody titers to the other group yielded the same findings. (4) Conclusions: In this study of life-threatening COVID-19 patients, CP was not associated with time to clinical improvement within 28 days, or hospital mortality.

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