The Type-Specific Neutralizing Antibody Response Elicited by a Dengue Vaccine Candidate Is Focused on Two Amino Acids of the Envelope Protein

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 of E2CD154 Subunit Vaccine Candidate against Classical Swine Fever in Piglets with Different Levels of Maternally Derived Antibodies

Vaccines ◽

10.3390/vaccines9010007 ◽

2020 ◽

Vol 9 (1) ◽

pp. 7

Author(s):

Yusmel Sordo-Puga ◽

Danny Pérez-Pérez ◽

Carlos Montero-Espinosa ◽

Aymé Oliva-Cárdenas ◽

Iliana Sosa-Teste ◽

...

Keyword(s):

Adverse Effects ◽

Classical Swine Fever Virus ◽

Envelope Protein ◽

Subunit Vaccine ◽

Vaccine Candidate ◽

Geometric Mean ◽

Classical Swine Fever ◽

Neutralizing Antibody ◽

Modified Live Vaccine ◽

Different Levels

E2CD154 is a novel subunit vaccine candidate against classical swine fever virus (CSFV). It contains the E2 envelope protein from CSFV fused to the porcine CD154 molecule formulated in the oil adjuvant MontanideTM ISA50 V2. Previous works evidenced the safety and immunogenicity of this candidate. Here, two other important parameters related to vaccine efficacy were assessed. First, the existence of high maternally derived antibody (MDA) titers in piglets born to sows vaccinated with E2CD154 was demonstrated. These MDA titers remained above 1:200 during the first seven weeks of life. To assess whether the titers interfere with active vaccination, 79 piglets from sows immunized with either E2CD154 or a modified live vaccine were vaccinated with E2CD154 following a 0–21-day biphasic schedule. Animals immunized at either 15, 21, or 33 days of age responded to vaccination by eliciting protective neutralizing antibody (NAb) titers higher than 1:600, with a geometric mean of 1:4335, one week after the booster. Those protective levels of NAb were sustained up to six months of age. No vaccination-related adverse effects were described. As a conclusion, E2CD154 is able to induce protective NAb in piglets with different MDA levels and at different days of age.

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Inactivation of Zika Virus by Photoactive Iodonaphthyl Azide Preserves Immunogenic Potential of the Virus

Pathogens ◽

10.3390/pathogens8040188 ◽

2019 ◽

Vol 8 (4) ◽

pp. 188

Author(s):

Austin ◽

Galasso ◽

Nickens ◽

Knollmann-Ritschel ◽

Sharma

Keyword(s):

Public Health ◽

Monoclonal Antibodies ◽

Antibody Response ◽

Vaccine Candidate ◽

Binding Capacity ◽

Neutralizing Antibody ◽

Vero Cells ◽

Productive Infection ◽

Public Health Importance ◽

Significant Public Health

Zika virus’s (ZIKV) emergence as a pathogen of significant public health importance has accelerated efforts to develop a ZIKV vaccine. To date, the need for an effective ZIKV vaccine is unmet. In this study, we report inactivation of ZIKV using a hydrophobic photoactive compound: 1, 5 iodonaphthyl azide (INA). 50 and 100 µM of INA completely inactivated ZIKV (INA-ZIKV). Western blot and ELISA analysis show some loss of the binding capacity of INA-iZIKV to anti-ZIKV monoclonal antibodies; however, immunization of mice with INA-iZIKV demonstrated seroconversion and ZIKV-neutralizing antibody response. RNA isolated from INA-iZIKV did not induce productive infection in Vero cells, suggesting inactivation of ZIKV RNA. These results suggest that in the absence of an approved ZIKV vaccine, INA-iZIKV can be pursued as a viable ZIKV vaccine candidate.

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A 12-Month–Interval Dosing Study in Adults Indicates That a Single Dose of the National Institute of Allergy and Infectious Diseases Tetravalent Dengue Vaccine Induces a Robust Neutralizing Antibody Response

The Journal of Infectious Diseases ◽

10.1093/infdis/jiw067 ◽

2016 ◽

Vol 214 (6) ◽

pp. 832-835 ◽

Cited By ~ 30

Author(s):

Anna P. Durbin ◽

Beth D. Kirkpatrick ◽

Kristen K. Pierce ◽

Marya P. Carmolli ◽

Cecilia M. Tibery ◽

...

Keyword(s):

Single Dose ◽

Infectious Diseases ◽

Antibody Response ◽

Neutralizing Antibody ◽

Dengue Vaccine

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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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