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

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.

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

Communications Biology ◽

10.1038/s42003-021-02128-8 ◽

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.

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Design of a Protective Single-Dose Intranasal Nanoparticle-Based Vaccine Platform for Respiratory Infectious Diseases

PLoS ONE ◽

10.1371/journal.pone.0017642 ◽

2011 ◽

Vol 6 (3) ◽

pp. e17642 ◽

Cited By ~ 81

Author(s):

Bret D. Ulery ◽

Devender Kumar ◽

Amanda E. Ramer-Tait ◽

Dennis W. Metzger ◽

Michael J. Wannemuehler ◽

...

Keyword(s):

Single Dose ◽

Infectious Diseases ◽

Vaccine Platform ◽

Respiratory Infectious Diseases

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Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19

10.1101/2021.06.22.21258961 ◽

2021 ◽

Author(s):

Chiara Agrati ◽

Stefania Capone ◽

Concetta Castilletti ◽

Eleonora Cimini ◽

Giulia Matusali ◽

...

Keyword(s):

Immune Response ◽

Single Dose ◽

Neutralizing Antibodies ◽

Small Sample Size ◽

Phase 1 ◽

Vaccination Campaign ◽

Small Sample ◽

Vaccine Platform ◽

Ideal Tool ◽

Cellular Immune

Here we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single administration GRAd-COV2 vaccine candidate in the context of the phase 1 clinical trial. We observed a clear boost of both binding/neutralizing antibodies as well as T cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single-dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.

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

10.1101/2021.05.25.21257797 ◽

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.

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

10.1101/2020.08.28.272518 ◽

2020 ◽

Cited By ~ 2

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.

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Replication-Defective West Nile Virus with NS1 Deletion as a New Vaccine Platform for Flavivirus

Journal of Virology ◽

10.1128/jvi.00720-19 ◽

2019 ◽

Vol 93 (17) ◽

Cited By ~ 2

Author(s):

Na Li ◽

Ya-Nan Zhang ◽

Cheng-Lin Deng ◽

Pei-Yong Shi ◽

Zhi-Ming Yuan ◽

...

Keyword(s):

Single Dose ◽

West Nile Virus ◽

Cell Line ◽

Vaccine Development ◽

Vero Cells ◽

High Dose ◽

Ns1 Protein ◽

Vaccine Platform ◽

West Nile ◽

Flavivirus Vaccine

ABSTRACTWe previously produced a replication-defective West Nile virus (WNV) lacking NS1 (WNV-ΔNS1) that could propagate at low levels (105infectious units [IU]/ml) in a 293T cell line expressing wild-type (WT) NS1. This finding indicates the potential of developing WNV-ΔNS1 as a noninfectious vaccine. To explore this idea, we developed an NS1-expressing Vero cell line (VeroNS1) that significantly improved the yield of WNV-ΔNS1 (108 IU/ml). We evaluated the safety and efficacy of WNV-ΔNS1 in mice. WNV-ΔNS1 appeared to be safe, as no replicative virus was found in naive Vero cells after continuous culturing of WNV-ΔNS1 in VeroNS1cells for 15 rounds. WNV-ΔNS1 was noninfectious in mice, even when IFNAR−/−mice were administered a high dose of WNV-ΔNS1. Vaccination with a single dose of WNV-ΔNS1 protected mice from a highly lethal challenge with WT WNV. The antibody response against WNV correlated well with the protection of vaccinated mice. Our study demonstrates the potential of the NS1transcomplementation system as a new platform for flavivirus vaccine development.IMPORTANCEMany flaviviruses are significant human pathogens that frequently cause outbreaks and epidemics around the world. Development of novel vaccine platforms against these pathogens is a public health priority. Using WNV as a model, we developed a new vaccine platform for flaviviruses. WNV containing a NS1 deletion (WNV-ΔNS1) could be efficientlytranscomplemented in Vero cells that constitutively expressed WT NS1 protein. A single-dose immunization with WNV-ΔNS1 elicited robust immune responses in mice. The immunized animals were fully protected against pathogenic WNV infection. No adverse effects related to the WNV-ΔNS1 vaccination were observed. The results have demonstrated the potential of the NS1 complementation system as an alternative platform for flavivirus vaccine development, especially for highly pathogenic flaviviruses.

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A virus-like particle vaccine platform elicits heightened and hastened local lung mucosal antibody production after a single dose

Vaccine ◽

10.1016/j.vaccine.2012.03.035 ◽

2012 ◽

Vol 30 (24) ◽

pp. 3653-3665 ◽

Cited By ~ 25

Author(s):

Laura E. Richert ◽

Amy E. Servid ◽

Ann L. Harmsen ◽

Agnieszka Rynda-Apple ◽

Soo Han ◽

...

Keyword(s):

Single Dose ◽

Antibody Production ◽

Vaccine Platform ◽

Mucosal Antibody ◽

Virus Like Particle

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599Rapid rises in antibody titers observed following single dose administration of a novel 4-antigen Staphylococcus aureus vaccine (SA4Ag) to healthy adults

Open Forum Infectious Diseases ◽

10.1093/ofid/ofu051.66 ◽

2014 ◽

Vol 1 (suppl_1) ◽

pp. S25-S25

Author(s):

Robert W. Frenck ◽

C. Buddy Creech ◽

Eric Sheldon ◽

David Seiden ◽

Martin K. Kankam ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Single Dose ◽

Healthy Adults ◽

Dose Administration ◽

Single Dose Administration ◽

Antibody Titers

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Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

Journal of Virology ◽

10.1128/jvi.00479-17 ◽

2017 ◽

Vol 91 (17) ◽

Cited By ~ 14

Author(s):

Nicholas J. Lennemann ◽

Andrew S. Herbert ◽

Rachel Brouillette ◽

Bethany Rhein ◽

Russell A. Bakken ◽

...

Keyword(s):

Single Dose ◽

West Africa ◽

Vesicular Stomatitis Virus ◽

Ebola Virus ◽

Dependent Manner ◽

Wild Type ◽

Vaccine Platform ◽

Virus Glycoprotein ◽

Conserved Regions ◽

Vesicular Stomatitis

ABSTRACT The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. The prime/boost regimen provided significantly better protection than a single dose. As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success. IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy.

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