Safety and protective efficacy of Salmonella Pullorum spiC and rfaH deletion rough mutant as a live attenuated DIVA vaccine candidate

AbstractVaccines remain the key protective measure to achieve herd immunity to control the disease burden and stop COVID-19 pandemic. We have developed and assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZyCoV-D (a plasmid DNA based vaccine candidates) administered through Needle Free Injection System (NFIS) and syringe-needle (intradermal) in rhesus macaques with three dose vaccine regimens. The vaccine candidate 2mg dose administered using Needle Free Injection System (NFIS) elicited a significant immune response with development of SARS-CoV-2 S1 spike region specific IgG and neutralizing antibody (NAb) titers during the immunization phase and significant enhancement in the levels after the virus challenge. In 2 mg NFIS group the IgG and NAb titers were maintained and showed gradual rise during the immunization period (15 weeks) and till 2 weeks after the virus challenge. It also conferred better protection to macaques evident by the viral clearance from nasal swab, throat swab and bronchoalveolar lavage fluid specimens in comparison with macaques from other immunized groups. In contrast, the animals from placebo group developed high levels of viremia and lung disease following the virus challenge. Besides this, the vaccine candidate also induced increase lymphocyte proliferation and cytokines response (IL-6, IL-5).The administration of the vaccine candidate with NFIS generated a better immunogenicity response in comparison to syringe-needle (intradermal route). The study demonstrated immunogenicity and protective efficacy of the vaccine candidate, ZyCoV-D in rhesus macaques.

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Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy

Science ◽

10.1126/science.abc4730 ◽

2020 ◽

pp. eabc4730 ◽

Cited By ~ 22

Author(s):

Hongjing Gu ◽

Qi Chen ◽

Guan Yang ◽

Lei He ◽

Hang Fan ◽

...

Keyword(s):

Vaccine Candidate ◽

Inflammatory Responses ◽

Protective Efficacy ◽

Small Animal ◽

Spike Protein ◽

Mouse Lung ◽

Receptor Binding Domain ◽

Intranasal Inoculation ◽

Adaptive Mutations ◽

Small Animal Models

The ongoing COVID-19 pandemic has prioritized the development of small animal models for SARS-CoV-2. Herein, we adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (termed MASCp6) showed increased infectivity in mouse lung, and led to interstitial pneumonia and inflammatory responses in both young and aged mice following intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.

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Reduction in Oviposition of Poultry Red Mite (Dermanyssus gallinae) in Hens Vaccinated with Recombinant Akirin

Vaccines ◽

10.3390/vaccines7030121 ◽

2019 ◽

Vol 7 (3) ◽

pp. 121 ◽

Cited By ~ 6

Author(s):

Jose Lima-Barbero ◽

Marinela Contreras ◽

Kathryn Bartley ◽

Daniel Price ◽

Francesca Nunn ◽

...

Keyword(s):

Egg Production ◽

Protective Antigen ◽

Vaccine Candidate ◽

Protective Efficacy ◽

Egg Yolk ◽

Economic Losses ◽

Dermanyssus Gallinae ◽

Poultry Red Mite ◽

Production Sector ◽

Worldwide Distribution

The poultry red mite (PRM), Dermanyssus gallinae, is a hematophagous ectoparasite of birds with worldwide distribution that causes economic losses in the egg-production sector of the poultry industry. Traditional control methods, mainly based on acaricides, have been only partially successful, and new vaccine-based interventions are required for the control of PRM. Vaccination with insect Akirin (AKR) and its homolog in ticks, Subolesin (SUB), have shown protective efficacy for the control of ectoparasite infestations and pathogen infection/transmission. The aim of this study was the identification of the akr gene from D. gallinae (Deg-akr), the production of the recombinant Deg-AKR protein, and evaluation of its efficacy as a vaccine candidate for the control of PRM. The anti-Deg-AKR serum IgY antibodies in hen sera and egg yolk were higher in vaccinated than control animals throughout the experiment. The results demonstrated the efficacy of the vaccination with Deg-AKR for the control of PRM by reducing mite oviposition by 42% following feeding on vaccinated hens. A negative correlation between the levels of serum anti-Deg-AKR IgY and mite oviposition was obtained. These results support Deg-AKR as a candidate protective antigen for the control of PRM population growth.

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