Reductions in Cross‐Neutralizing Antibody Responses in Infants after Attenuation of the Human Rotavirus Vaccine Candidate 89‐12

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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Immunogenicity Studies of Bivalent Inactivated Virions of EV71/CVA16 Formulated with Submicron Emulsion Systems

BioMed Research International ◽

10.1155/2014/670506 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Chih-Wei Lin ◽

Chia-Chyi Liu ◽

Tsung-Chun Lu ◽

Shih-Jen Liu ◽

Yen-Hung Chow ◽

...

Keyword(s):

Single Dose ◽

Vaccine Candidate ◽

Emerging Infectious Diseases ◽

Foot And Mouth Disease ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Submicron Particles ◽

Emulsion Systems ◽

Submicron Emulsion ◽

Immunogenicity Study

We assessed two strategies for preparing candidate vaccines against hand, foot, and mouth disease (HFMD) caused mainly by infections of enterovirus (EV) 71 and coxsackievirus (CV) A16. We firstly design and optimize the potency of adjuvant combinations of emulsion-based delivery systems, using EV71 candidate vaccine as a model. We then perform immunogenicity studies in mice of EV71/CVA16 antigen combinations formulated with PELC/CpG. A single dose of inactivated EV71 virion (0.2 μg) emulsified in submicron particles was found (i) to induce potent antigen-specific neutralizing antibody responses and (ii) consistently to elicit broad antibody responses against EV71 neutralization epitopes. A single dose immunogenicity study of bivalent activated EV71/CVA16 virion formulated with either Alum or PELC/CpG adjuvant showed that CVA16 antigen failed to elicit CVA16 neutralizing antibody responses and did not affect EV71-specific neutralizing antibody responses. A boosting dose of emulsified EV71/CVA16 bivalent vaccine candidate was found to be necessary to achieve high seroconversion of CVA16-specific neutralizing antibody responses. The current results are important for the design and development of prophylactic vaccines against HFMD and other emerging infectious diseases.

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CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease Following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology

Vaccines ◽

10.3390/vaccines9111346 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1346

Author(s):

Jennifer K. DeMarco ◽

Joshua M. Royal ◽

William E. Severson ◽

Jon D. Gabbard ◽

Steve Hume ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Potential Role ◽

Vaccine Candidate ◽

Severe Disease ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Receptor Binding Domain ◽

Symptomatic Disease ◽

Human Igg1

We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.

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Development of a high-growth enterovirus 71 vaccine candidate inducing cross-reactive neutralizing antibody responses

Vaccine ◽

10.1016/j.vaccine.2018.01.041 ◽

2018 ◽

Vol 36 (9) ◽

pp. 1167-1173 ◽

Cited By ~ 1

Author(s):

Min-Yuan Chia ◽

Wan-Yu Chung ◽

Chun-Hsiung Wang ◽

Wei-Hau Chang ◽

Min-Shi Lee

Keyword(s):

Vaccine Candidate ◽

Enterovirus 71 ◽

High Growth ◽

Neutralizing Antibody ◽

Antibody Responses

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Early phase II trial of human rotavirus vaccine candidate RV3

Vaccine ◽

10.1016/s0264-410x(02)00235-9 ◽

2002 ◽

Vol 20 (23-24) ◽

pp. 2950-2956 ◽

Cited By ~ 60

Author(s):

G BARNES

Keyword(s):

Phase Ii ◽

Early Phase ◽

Vaccine Candidate ◽

Phase Ii Trial ◽

Rotavirus Vaccine ◽

Human Rotavirus

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Immunogenicity and protective efficacy of one- and two-dose regimens of the Ad26.COV2.S COVID-19 vaccine candidate in adult and aged rhesus macaques

10.1101/2020.11.17.368258 ◽

2020 ◽

Author(s):

Laura Solforosi ◽

Harmjan Kuipers ◽

Sietske K. Rosendahl Huber ◽

Joan E.M. van der Lubbe ◽

Liesbeth Dekking ◽

...

Keyword(s):

Single Dose ◽

Vaccine Candidate ◽

Protective Efficacy ◽

Rhesus Macaques ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Upper Respiratory Tract ◽

Post Dose ◽

Early Indication

AbstractSafe and effective coronavirus disease (COVID)-19 vaccines are urgently needed to control the ongoing pandemic. While single-dose vaccine regimens would provide multiple advantages, two doses may improve the magnitude and durability of immunity and protective efficacy. We assessed one- and two-dose regimens of the Ad26.COV2.S vaccine candidate in adult and aged non-human primates (NHP). A two-dose Ad26.COV2.S regimen induced higher peak binding and neutralizing antibody responses compared to a single dose. In one-dose regimens neutralizing antibody responses were stable for at least 14 weeks, providing an early indication of durability. Ad26.COV2.S induced humoral immunity and Th1 skewed cellular responses in aged NHP that were comparable to adult animals. Importantly, aged Ad26.COV2.S-vaccinated animals challenged 3 months post -dose 1 with a SARS-CoV-2 spike G614 variant showed near complete lower and substantial upper respiratory tract protection for both regimens. These are the first NHP data showing COVID-19 vaccine protection against the SARS-CoV-2 spike G614 variant and support ongoing clinical Ad26.COV2.S development.SummaryCOVID-19 vaccines are urgently needed and while single-dose vaccines are preferred, two-dose regimens may improve efficacy. We show improved Ad26.COV2.S immunogenicity in non-human primates after a second vaccine dose, while both regimens protected aged animals against SARS-CoV-2 disease.

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Lactobacilli and Bifidobacteria enhance mucosal B cell responses and differentially modulate systemic antibody responses to an oral human rotavirus vaccine in a neonatal gnotobiotic pig disease model

Gut Microbes ◽

10.4161/19490976.2014.969972 ◽

2014 ◽

Vol 5 (5) ◽

pp. 639-651 ◽

Cited By ~ 59

Author(s):

Sukumar Kandasamy ◽

Kuldeep S Chattha ◽

Anastasia N Vlasova ◽

Gireesh Rajashekara ◽

Linda J Saif

Keyword(s):

B Cell ◽

Disease Model ◽

Antibody Responses ◽

Rotavirus Vaccine ◽

Cell Responses ◽

Human Rotavirus ◽

B Cell Responses ◽

Gnotobiotic Pig

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Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle

Vaccines ◽

10.3390/vaccines9111347 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1347

Author(s):

Joshua M. Royal ◽

Carrie A. Simpson ◽

Alison A. McCormick ◽

Amanda Phillips ◽

Steve Hume ◽

...

Keyword(s):

Tobacco Mosaic Virus ◽

Mosaic Virus ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Nano Particle ◽

Th2 Response ◽

Adjuvanted Vaccine ◽

Human Igg1

Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.

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