scholarly journals Experimental Vesicular Stomatitis in Swine: Effects of Route of Inoculation and Steroid Treatment

1997 ◽  
Vol 9 (2) ◽  
pp. 136-142 ◽  
Author(s):  
Elizabeth W. Howerth ◽  
David E. Stallknecht ◽  
Mark Dorminy ◽  
Tracy Pisell ◽  
Gerard R. Clarke
Keyword(s):  
Soft Palate ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Steroid Treatment ◽  
Sand Fly ◽  
Virus Shedding ◽  
Viral Shedding ◽  
Contact Transmission ◽  
Vesicular Stomatitis ◽  
Experimental Trials

An enzootic focus of vesicular stomatitis virus New Jersey serotype (VSV-NJ) exists on Ossabaw Island, Georgia. Many questions regarding the epizootiology of this virus at this focus still exist, but evidence suggests that the vector for this virus is a phlebotomine sand fly ( Lutzomyia shannoni), with feral swine serving as a potential source of virus for the sand fly and for other swine via contact transmission. We conducted 2 experimental trials in domestic swine using VSV-NJ isolated from a sand fly from Ossabaw Island to determine if route of inoculation or immunosuppression via steroid administration affected the development of disease, viremia, viral shedding, or the neutralizing antibody response. In a third trial, we studied the potential for contact transmission among swine using this isolate. Virus isolations were made from nasal cavity or palatine tonsil of the soft palate, and VSV-NJ neutralizing antibodies developed when pigs were inoculated intradermally in the apex of the snout, ear, or coronary band, intravenously, intranasally, or via scarification of the apex of the snout or coronary band. Vesicles developed only in pigs inoculated in the apex of the snout or coronary band, and these vesicles were at the site of inoculation. Steroid treatment did not potentiate the development of secondary vesicles and did not prolong the period of virus shedding from VSV-NJ-infected swine. Contact transmission, as determined by shedding of virus from the tonsil of the soft palate and the development of VSV-NJ neutralizing antibodies, occurred in pigs in contact with animals inoculated in the apex of the snout but not in contact animals exposed to pigs inoculated intradermally in the coronary band or intranasally. These trials show that contact transmission can occur and VSV-NJ can be shed without the development of clinical disease (i.e., vesicle formation). Viremia was never detected in any of the experimental pigs, suggesting that swine may not be a good amplifying host for VSV-NJ.

scholarly journals Experimental infection of domestic dogs and cats with SARS-CoV-2: Pathogenesis, transmission, and response to reexposure in cats

2020 ◽  
Vol 117 (42) ◽  
pp. 26382-26388 ◽  
Author(s):  
Angela M. Bosco-Lauth ◽  
Airn E. Hartwig ◽  
Stephanie M. Porter ◽  
Paul W. Gordy ◽  
Mary Nehring ◽  
...  
Keyword(s):  
Antibody Response ◽  
Acute Infection ◽  
Clinical Signs ◽  
Neutralizing Antibody ◽  
Human Infection ◽  
Vaccine Strategy ◽  
Animal Reservoir ◽  
Viral Shedding ◽  
Contact Transmission ◽  
Infection Resistance

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached nearly every country in the world with extraordinary person-to-person transmission. The most likely original source of the virus was spillover from an animal reservoir and subsequent adaptation to humans sometime during the winter of 2019 in Wuhan Province, China. Because of its genetic similarity to SARS-CoV-1, it is probable that this novel virus has a similar host range and receptor specificity. Due to concern for human–pet transmission, we investigated the susceptibility of domestic cats and dogs to infection and potential for infected cats to transmit to naive cats. We report that cats are highly susceptible to infection, with a prolonged period of oral and nasal viral shedding that is not accompanied by clinical signs, and are capable of direct contact transmission to other cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection, but are unlikely to develop clinical disease. Further, we document that cats developed a robust neutralizing antibody response that prevented reinfection following a second viral challenge. Conversely, we found that dogs do not shed virus following infection but do seroconvert and mount an antiviral neutralizing antibody response. There is currently no evidence that cats or dogs play a significant role in human infection; however, reverse zoonosis is possible if infected owners expose their domestic pets to the virus during acute infection. Resistance to reinfection holds promise that a vaccine strategy may protect cats and, by extension, humans.

scholarly journals Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats

2020 ◽  
Author(s):  
Angela M. Bosco-Lauth ◽  
Airn E. Hartwig ◽  
Stephanie M. Porter ◽  
Paul W. Gordy ◽  
Mary Nehring ◽  
...  
Keyword(s):  
Antibody Response ◽  
Acute Infection ◽  
Clinical Signs ◽  
Neutralizing Antibody ◽  
Domestic Cats ◽  
Vaccine Strategy ◽  
Animal Reservoir ◽  
Viral Shedding ◽  
Contact Transmission ◽  
Infection Resistance

AbstractThe pandemic caused by SARS-CoV-2 has reached nearly every country in the world with extraordinary person-to-person transmission. The most likely original source of the virus was spillover from an animal reservoir and subsequent adaptation to humans sometime during the winter of 2019 in Wuhan Province, China. Because of its genetic similarity to SARS-CoV-1, it is likely that this novel virus has a similar host range and receptor specificity. Due to concern for human-pet transmission, we investigated the susceptibility of domestic cats and dogs to infection and potential for infected cats to transmit to naïve cats. We report that cats are highly susceptible to subclinical infection, with a prolonged period of oral and nasal viral shedding that is not accompanied by clinical signs, and are capable of direct contact transmission to other cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection, but are unlikely to develop clinical disease. Further, we document that cats develop a robust neutralizing antibody response that prevented re-infection to a second viral challenge. Conversely, we found that dogs do not shed virus following infection, but do mount an anti-viral neutralizing antibody response. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis is possible if infected owners expose their domestic pets during acute infection. Resistance to re-exposure holds promise that a vaccine strategy may protect cats, and by extension humans, to disease susceptibility.

scholarly journals SARS-CoV-2 Virus like Particles produced by a single recombinant baculovirus generate potent neutralizing antibody that protects against variant challenge

2021 ◽  
Author(s):  
Edward Sullivan ◽  
Po-yu Sung ◽  
Weining Wu ◽  
Neil Berry ◽  
Sarah Kempster ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Expression System ◽  
Recombinant Baculovirus ◽  
Neutralizing Antibody ◽  
Structural Proteins ◽  
Lung Pathology ◽  
Challenge Virus ◽  
Virus Shedding ◽  
Virus Like Particles

The Covid-19 pandemic caused by SARS-CoV-2 infection has highlighted the need for the rapid generation of efficient vaccines for emerging disease. Virus-like particles, VLPs, are an established vaccine technology that produces virus-like mimics, based on expression of the structural proteins of a target virus that can stimulate strong neutralizing antibody responses. SARS-CoV-2 is a coronavirus where the basis of VLP formation has been shown to be the co-expression of the spike, membrane and envelope structural proteins. Here we describe the generation of SARS-CoV-2 VLPs by the co expression of the salient structural proteins in insect cells using the established baculovirus expression system. VLPs were heterologous ~100nm diameter enveloped particles with a distinct fringe that reacted strongly with SARS-CoV-2 convalescent sera. In a Syrian hamster challenge model, a non adjuvanted VLPs induced neutralizing antibodies to the VLP-associated Wuhan S protein, reduced virus shedding following a virulent challenge with SARS-CoV-2 (B.1.1.7 variant) and protected against disease associated weight loss. Immunized animals showed reduced lung pathology and lower challenge virus replication than the non-immunized controls. Our data, using an established and scalable technology, suggest SARS-CoV-2 VLPs offer an efficient vaccine that mitigates against virus load and prevents severe disease.

scholarly journals Recombinant adenovirus expressing vesicular stomatitis virus G proteins induce both humoral and cell-mediated immune responses in mice and goats

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Xiaojuan Xue ◽  
Zhaorong Yu ◽  
Hongyan Jin ◽  
Lin Liang ◽  
Jiayang Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
G Proteins ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Recombinant Adenovirus ◽  
Neutralizing Antibody ◽  
Negative Control ◽  
Antibody Titers ◽  
Vesicular Stomatitis ◽  
Cellular Immune

Abstract Background Vesicular stomatitis (VS) is an acute, highly contagious and economically important zoonotic disease caused by the vesicular stomatitis virus (VSV). There is a need for effective and safe stable recombinant vaccine for the control of the disease. The human type 5 replication-defective adenovirus expression vector is a good way to construct recombinant vaccines. Results Three recombinant adenoviruses (rAd) were successfully constructed that expressed the VSV Indiana serotype glycoprotein (VSV-IN-G), VSV New Jersey serotype glycoprotein (VSV-NJ-G), and the G fusion protein (both serotypes of G [VSV-IN-G-NJ-G]) with potentiality to induce protective immunity. G proteins were successfully expressed with good immunogenicity. The rAds could induce the production of VSV antibodies in mice, and VSV neutralizing antibodies in goats, respectively. The neutralizing antibody titers could reach 1:32 in mice and 1:64 in goats. The rAds induced strong lymphocyte proliferation in mice and goats, which was significantly higher compared to the negative control groups. Conclusions The three rAds constructed in the study expressed VSV-G proteins and induced both humoral and cellular immune responses in mice and goats. These results lay the foundation for further studies on the use of rAds in vaccines expressing VSV-G.

scholarly journals Virological Characterization of the First 2 COVID-19 Patients Diagnosed in Italy: Phylogenetic Analysis, Virus Shedding Profile From Different Body Sites, and Antibody Response Kinetics

2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Francesca Colavita ◽  
Daniele Lapa ◽  
Fabrizio Carletti ◽  
Eleonora Lalle ◽  
Francesco Messina ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Clinical Manifestations ◽  
Neutralizing Antibody ◽  
Laboratory Diagnosis ◽  
Viral Rna ◽  
Clinical Samples ◽  
Serum Samples ◽  
Virus Shedding ◽  
Modes Of Transmission

Abstract Background The pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unclear. We report the detection of viral RNA from different anatomical districts and the antibody profile in the first 2 COVID-19 cases diagnosed in Italy. Methods We tested for SARS-CoV-2 RNA clinical samples, either respiratory and nonrespiratory (ie, saliva, serum, urine, vomit, rectal, ocular, cutaneous, and cervico-vaginal swabs), longitudinally collected from both patients throughout the hospitalization. Serological analysis was carried out on serial serum samples to evaluate IgM, IgA, IgG, and neutralizing antibody levels. Results SARS-CoV-2 RNA was detected since the early phase of illness, lasting over 2 weeks in both upper and lower respiratory tract samples. Virus isolate was obtained from acute respiratory samples, while no infectious virus was rescued from late respiratory samples with low viral RNA load, collected when serum antibodies had been developed. Several other specimens came back positive, including saliva, vomit, rectal, cutaneous, cervico-vaginal, and ocular swabs. IgM, IgA, and IgG were detected within the first week of diagnosis, with IgG appearing earlier and at higher titers. Neutralizing antibodies developed during the second week, reaching high titers 32 days after diagnosis. Conclusions Our longitudinal analysis showed that SARS-CoV-2 RNA can be detected in different body samples, which may be associated with broad tropism and different spectra of clinical manifestations and modes of transmission. Profiling antibody response and neutralizing activity can assist in laboratory diagnosis and surveillance actions.

scholarly journals Recombinant Adenovirus Expressing Vesicular Stomatitis Virus G Proteins Induce both Humoral and Cell-mediated Immune Responses in Mice and Goats

2021 ◽  
Author(s):  
Xiaojuan Xue ◽  
Zhaorong Yu ◽  
Hongyan Jin ◽  
Lin Liang ◽  
Jiayang Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
G Proteins ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Recombinant Adenovirus ◽  
Neutralizing Antibody ◽  
Negative Control ◽  
Antibody Titers ◽  
Vesicular Stomatitis ◽  
Cellular Immune

Abstract Background: Vesicular stomatitis (VS) is an acute, highly contagious and economically important zoonotic disease caused by the vesicular stomatitis virus (VSV). There is a need for effective and safe stable recombinant vaccine for the control of the disease. The human type 5 replication-defective adenovirus expression vector is a good way to construct recombinant vaccines.Results: Three recombinant adenoviruses (rAd) were successfully constructed that expressed the VSV Indiana serotype glycoprotein (VSV-IN-G), VSV New Jersey serotype glycoprotein (VSV-NJ-G), and the G fusion protein (both serotypes of G [VSV-IN-G-NJ-G]) with potentiality to induce protective immunity. G proteins were successfully expressed with good immunogenicity. The rAds could induce the production of VSV antibodies in mice, and VSV neutralizing antibodies in goats, respectively. The neutralizing antibody titers could reach 1:32 in mice and 1:64 in goats. The rAds induced strong lymphocyte proliferation in mice and goats, which was significantly higher compared to the negative control groups. Conclusions: The three rAds constructed in the study expressed VSV-G proteins and induced both humoral and cellular immune responses in mice and goats. These results lay the foundation for further studies on the use of rAds in vaccines expressing VSV-G.

scholarly journals Models to inform neutralizing antibody therapy strategies during pandemics: the case of SARS-CoV-2

2021 ◽  
Vol 4 (1) ◽  
pp. 60-71
Author(s):  
Donovan Guttieres ◽  
Anthony J Sinskey ◽  
Stacy L Springs
Keyword(s):  
Value Chain ◽  
Neutralizing Antibodies ◽  
Resource Constraints ◽  
Antibody Therapy ◽  
Neutralizing Antibody ◽  
Epidemiological Data ◽  
Production Costs ◽  
Production Scale ◽  
Design And Optimization ◽  
Critical Components

Abstract Background Neutralizing antibodies (nAbs) against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) can play an important role in reducing impacts of the COVID-19 pandemic, complementing ongoing public health efforts such as diagnostics and vaccination. Rapidly designing, manufacturing and distributing nAbs requires significant planning across the product value chain and an understanding of the opportunities, challenges and risks throughout. Methods A systems framework comprised of four critical components is presented to aid in developing effective end-to-end nAbs strategies in the context of a pandemic: (1) product design and optimization, (2) epidemiology, (3) demand and (4) supply. Quantitative models are used to estimate product demand using available epidemiological data, simulate biomanufacturing operations from typical bioprocess parameters and calculate antibody production costs to meet clinical needs under various realistic scenarios. Results In a US-based case study during the 9-month period from March 15 to December 15, 2020, the projected number of SARS-CoV-2 infections was 15.73 million. The estimated product volume needed to meet therapeutic demand for the maximum number of clinically eligible patients ranged between 6.3 and 31.5 tons for 0.5 and 2.5 g dose sizes, respectively. The relative production scale and cost needed to meet demand are calculated for different centralized and distributed manufacturing scenarios. Conclusions Meeting demand for anti-SARS-CoV-2 nAbs requires significant manufacturing capacity and planning for appropriate administration in clinical settings. MIT Center for Biomedical Innovation’s data-driven tools presented can help inform time-critical decisions by providing insight into important operational and policy considerations for making nAbs broadly accessible, while considering time and resource constraints.

scholarly journals Design and Characterization of a DNA Vaccine Based on Spike with Consensus Nucleotide Sequence against Infectious Bronchitis Virus

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 50
Author(s):  
Lei Zuo ◽  
Wenjun Yan ◽  
Zhou Song ◽  
Hao Li ◽  
Xin Xie ◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Dna Vaccine ◽  
Infectious Bronchitis Virus ◽  
Neutralizing Antibody ◽  
Economic Losses ◽  
Post Translational Modification ◽  
Virus Shedding ◽  
Infectious Bronchitis ◽  
Specific Pathogen ◽  
Cellular Immune

Avian coronavirus infectious bronchitis virus (IBV) causes severe economic losses in the poultry industry, but its control is hampered by the continuous emergence of new genotypes and the lack of cross-protection among different IBV genotypes. We designed a new immunogen based on a spike with the consensus nucleotide sequence (S_con) that may overcome the extraordinary genetic diversity of IBV. S_con was cloned into a pVAX1 vector to form a new IBV DNA vaccine, pV-S_con. pV-S_con could be correctly expressed in HD11 cells with corresponding post-translational modification, and induced a neutralizing antibody response to the Vero-cell-adapted IBV strain Beaudette (p65) in mice. To further evaluate its immunogenicity, specific-pathogen-free (SPF) chickens were immunized with the pV-S_con plasmid and compared with the control pVAX1 vector and the H120 vaccine. Detection of IBV-specific antibodies and cell cytokines (IL-4 and IFN-γ) indicated that vaccination with pV-S_con efficiently induced both humoral and cellular immune responses. After challenge with the heterologous strain M41, virus shedding and virus loading in tissues was significantly reduced both by pV-S_con and its homologous vaccine H120. Thus, pV-S_con is a promising vaccine candidate for IBV, and the consensus approach is an appealing method for vaccine design in viruses with high variability.

scholarly journals Neutralizing Antibody Therapeutics for COVID-19

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 628
Author(s):  
Aeron C. Hurt ◽  
Adam K. Wheatley
Keyword(s):  
High Risk ◽  
Neutralizing Antibodies ◽  
Controlled Trial ◽  
Antiviral Treatment ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Supplemental Oxygen ◽  
European Medicines Agency ◽  
Global Public Health ◽  
Public Health Burden

The emergence of SARS-CoV-2 and subsequent COVID-19 pandemic has resulted in a significant global public health burden, leading to an urgent need for effective therapeutic strategies. In this article, we review the role of SARS-CoV-2 neutralizing antibodies (nAbs) in the clinical management of COVID-19 and provide an overview of recent randomized controlled trial data evaluating nAbs in the ambulatory, hospitalized and prophylaxis settings. Two nAb cocktails (casirivimab/imdevimab and bamlanivimab/etesevimab) and one nAb monotherapy (bamlanivimab) have been granted Emergency Use Authorization by the US Food and Drug Administration for the treatment of ambulatory patients who have a high risk of progressing to severe disease, and the European Medicines Agency has similarly recommended both cocktails and bamlanivimab monotherapy for use in COVID-19 patients who do not require supplemental oxygen and who are at high risk of progressing to severe COVID-19. Efficacy of nAbs in hospitalized patients with COVID-19 has been varied, potentially highlighting the challenges of antiviral treatment in patients who have already progressed to severe disease. However, early data suggest a promising prophylactic role for nAbs in providing effective COVID-19 protection. We also review the risk of treatment-emergent antiviral resistant “escape” mutants and strategies to minimize their occurrence, discuss the susceptibility of newly emerging SARS-COV-2 variants to nAbs, as well as explore administration challenges and ways to improve patient access.

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