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 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 Single-dose SARS-CoV-2 vaccine in a prospective cohort of COVID-19 patients

2021 ◽  
Author(s):  
Marit J. van Gils ◽  
Hugo D.G. Willegen ◽  
Elke Wynberg ◽  
Alvin X. Han ◽  
Karlijn van der Straten ◽  
...  
Keyword(s):  
Single Dose ◽  
Prospective Cohort ◽  
Serum Antibody ◽  
Neutralizing Antibody ◽  
Credible Interval ◽  
Time Interval ◽  
Vaccine Response ◽  
Vaccine Strategy ◽  
Igg Antibody ◽  
Antibody Titers

Background The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies, particularly single vaccine dosing of individuals with prior SARS-CoV-2 infection. Methods We evaluated SARS-CoV-2 specific antibody responses following a single-dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine in 155 previously SARS-CoV-2-infected individuals participating in a population-based prospective cohort study of COVID-19 patients. Participants varied widely in age, comorbidities, COVID-19 severity and time since infection, ranging from 1 to 15 months. Serum antibody titers were determined at time of vaccination and one week after vaccination. Responses were compared to those in SARS-CoV-2-naive health care workers after two BNT162b2 mRNA vaccine doses. Results Within one week of vaccination, IgG antibody levels to virus spike and RBD proteins increased 27 to 29-fold and neutralizing antibody titers increased 12-fold, exceeding titers of fully vaccinated SARS-CoV-2-naive controls (95% credible interval (CrI): 0.56 to 0.67 v. control 95% CrI: -0.16 to -0.02). Pre-vaccination neutralizing antibody titers had the largest positive mean effect size on titers following vaccination (95% CrI (0.16 to 0.45)). COVID-19 severity, the presence of comorbidities and the time interval between infection and vaccination had no discernible impact on vaccine response. Conclusion A single dose of BNT162b2 mRNA vaccine up to 15 months after SARS-CoV-2 infection provides neutralizing titers exceeding two vaccine doses in previously uninfected individuals. These findings support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection.

scholarly journals A single immunization with spike-functionalized ferritin vaccines elicits neutralizing antibody responses against SARS-CoV-2 in mice

2020 ◽  
Author(s):  
Abigail E. Powell ◽  
Kaiming Zhang ◽  
Mrinmoy Sanyal ◽  
Shaogeng Tang ◽  
Payton A. Weidenbacher ◽  
...  
Keyword(s):  
Single Dose ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Receptor Binding Domain ◽  
Amino Acid Deletion ◽  
Vaccine Candidates ◽  
Self Assembling ◽  
Antibody Titers

AbstractDevelopment of a safe and effective SARS-CoV-2 vaccine is a public health priority. We designed subunit vaccine candidates using self-assembling ferritin nanoparticles displaying one of two multimerized SARS-CoV-2 spikes: full-length ectodomain (S-Fer) or a C-terminal 70 amino-acid deletion (SΔC-Fer). Ferritin is an attractive nanoparticle platform for production of vaccines and ferritin-based vaccines have been investigated in humans in two separate clinical trials. We confirmed proper folding and antigenicity of spike on the surface of ferritin by cryo-EM and binding to conformation-specific monoclonal antibodies. After a single immunization of mice with either of the two spike ferritin particles, a lentiviral SARS-CoV-2 pseudovirus assay revealed mean neutralizing antibody titers at least 2-fold greater than those in convalescent plasma from COVID-19 patients. Additionally, a single dose of SΔC-Fer elicited significantly higher neutralizing responses as compared to immunization with the spike receptor binding domain (RBD) monomer or spike ectodomain trimer alone. After a second dose, mice immunized with SΔC-Fer exhibited higher neutralizing titers than all other groups. Taken together, these results demonstrate that multivalent presentation of SARS-CoV-2 spike on ferritin can notably enhance elicitation of neutralizing antibodies, thus constituting a viable strategy for single-dose vaccination against COVID-19.

A single dose polyanhydride-based vaccine platform promotes and maintains anti-GnRH antibody titers

Vaccine ◽  
2018 ◽  
Vol 36 (7) ◽  
pp. 1016-1023 ◽  
Author(s):  
Robert G. Schaut ◽  
Matthew T. Brewer ◽  
Jesse M. Hostetter ◽  
Kriscelle Mendoza ◽  
Julia E. Vela-Ramirez ◽  
...  
Keyword(s):  
Single Dose ◽  
Vaccine Platform ◽  
Antibody Titers

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 A Single Dose of Self-Transcribing and Replicating RNA Based SARS-CoV-2 Vaccine Produces Protective Adaptive Immunity In Mice

2020 ◽  
Author(s):  
Ruklanthi de Alwis ◽  
Esther S Gan ◽  
Shiwei Chen ◽  
Yan Shan Leong ◽  
Hwee Cheng Tan ◽  
...  
Keyword(s):  
Single Dose ◽  
Intracellular Cytokine Staining ◽  
Neutralizing Antibody ◽  
Cell Mediated Immunity ◽  
Spike Glycoprotein ◽  
T Helper Lymphocytes ◽  
Antibody Titers ◽  
Replicase Complex ◽  
Ifn Γ ◽  
Dose Vaccine

ABSTRACTA self-transcribing and replicating RNA (STARR™) based vaccine (LUNAR®-COV19) has been developed to prevent SARS-CoV-2 infection. The vaccine encodes an alphavirus-based replicon and the SARS-CoV-2 full length spike glycoprotein. Translation of the replicon produces a replicase complex that amplifies and prolong SARS-CoV-2 spike glycoprotein expression. A single prime vaccination in mice led to robust antibody responses, with neutralizing antibody titers increasing up to day 60. Activation of cell mediated immunity produced a strong viral antigen specific CD8+ T lymphocyte response. Assaying for intracellular cytokine staining for IFN-γ and IL-4 positive CD4+ T helper lymphocytes as well as anti-spike glycoprotein IgG2a/IgG1 ratios supported a strong Th1 dominant immune response. Finally, single LUNAR-COV19 vaccination at both 2 μg and 10 μg doses completely protected human ACE2 transgenic mice from both mortality and even measurable infection following wild-type SARS-CoV-2 challenge. Our findings collectively suggest the potential of Lunar-COV19 as a single dose vaccine.

scholarly journals Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

2016 ◽  
Vol 113 (29) ◽  
pp. E4133-E4142 ◽  
Author(s):  
Jasdave S. Chahal ◽  
Omar F. Khan ◽  
Christopher L. Cooper ◽  
Justine S. McPartlan ◽  
Jonathan K. Tsosie ◽  
...  
Keyword(s):  
Single Dose ◽  
Toxoplasma Gondii ◽  
Protective Immunity ◽  
Ebola Virus ◽  
H1n1 Influenza ◽  
Antibody Responses ◽  
Emerging Pathogens ◽  
Vaccine Platform ◽  
Production Methods ◽  
Multiple Antigen

Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8+ T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.

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.

Sign in / Sign up

Export Citation Format

Share Document