Progression and Resolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Golden Syrian Hamsters

Mulka, Kathleen; Beck, Sarah E.; Solis, Clarisse V.; Johanson, Andrew; Queen, Suzanne E.; McCarron, Megan E.; Richardson, Morgan R.; Zhou, Ruifeng; Marinho, Paula; Jedlicka, Anne; Guerrero-Martin, Selena M.; Shirk, Erin N.; Braxton, Alicia M.; Brockhurst, Jacqueline; Creisher, Patrick S.; Dhakal, Santosh; Brayton, Cory; Veenhuis, Rebecca T.; Pate, Kelly A. Metcalf; Karakousis, Petros C.; Zahnow, Cynthia A.; Klein, Sabra L.; Jain, Sanjay; Tarwater, Patrick M.; Pekosz, Andrew; Villano, Jason; Mankowski, Joseph L.; Betenbaugh, Michael J.; Carlson, Bess; Castell, Natalie; Castillo, Jennie Ruelas; Flavahan, Kelly; Hutchinson, Eric K.; Littlefield, Kirsten; Looney, Monika; Lowman, Maggie; Majewski, Natalia; Maxwell, Amanda; Mota, Fernando; Mueller, Alice; Ordoñez, Alvaro A.; Pieterse, Lisa; Quijada, Darla; Ruiz-Bedoya, Camilo A.; Stover, Mitchel Graham; Vistein, Rachel; Wood, Melissa

doi:10.1016/j.ajpath.2021.10.009

Cited by 25 publications

(50 citation statements)

References 42 publications

(73 reference statements)

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“…Immunopositivity for Iba-1 (macrophages) by IHC provides a useful orthogonal measure of tissue lesions that correlates with overall clinical disease irrespective of lung expansion in hamsters. 9,24,27,38 In this study, we did not detect robust differences in IgG treatment groups, likely related to samples being collected prior to the peak of macrophage inflammation. We did notice a trend toward decreased numbers of CD3+ T lymphocytes in the lungs of IgG-treated hamsters, but this did not correspond to maximum weight loss.…”

Section: Discussioncontrasting

confidence: 56%

Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune sera: Quantitative image analysis in pathologic assessments

Piedra-Mora

Robinson

Tostanoski³

et al. 2022

Vet Pathol

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There is a need to standardize pathologic endpoints in animal models of SARS-CoV-2 infection to help benchmark study quality, improve cross-institutional comparison of data, and assess therapeutic efficacy so that potential drugs and vaccines for SARS-CoV-2 can rapidly advance. The Syrian hamster model is a tractable small animal model for COVID-19 that models clinical disease in humans. Using the hamster model, the authors used traditional pathologic assessment with quantitative image analysis to assess disease outcomes in hamsters administered polyclonal immune sera from previously challenged rhesus macaques. The authors then used quantitative image analysis to assess pathologic endpoints across studies performed at different institutions using different tissue processing protocols. The authors detail pathological features of SARS-CoV-2 infection longitudinally and use immunohistochemistry to quantify myeloid cells and T lymphocyte infiltrates during SARS-CoV-2 infection. High-dose immune sera protected hamsters from weight loss and diminished viral replication in tissues and reduced lung lesions. Cumulative pathology scoring correlated with weight loss and was robust in distinguishing IgG efficacy. In formalin-infused lungs, quantitative measurement of percent area affected also correlated with weight loss but was less robust in non-formalin-infused lungs. Longitudinal immunohistochemical assessment of interstitial macrophage infiltrates showed that peak infiltration corresponded to weight loss, yet quantitative assessment of macrophage, neutrophil, and CD3+ T lymphocyte numbers did not distinguish IgG treatment effects. Here, the authors show that quantitative image analysis was a useful adjunct tool for assessing SARS-CoV-2 treatment outcomes in the hamster model.

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Section: Discussioncontrasting

confidence: 56%

Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune sera: Quantitative image analysis in pathologic assessments

Piedra-Mora

Robinson

Tostanoski³

et al. 2022

Vet Pathol

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“…We report that this technology efficiently couples a SpyTag-RBD fusion protein produced in mammalian cell culture onto bacterial OMVs, resulting in RBD-OMVs that are recognized by antibodies against SARS-CoV-2. Furthermore, we show that intranasal vaccination with RBD-OMVs elicits antibodies, including neutralization responses against both wild-type and Delta viral variants, and confers protection against challenge with SARS-CoV-2 in a recently developed hamster model Mulka et al, 2021).…”

Section: Introductionmentioning

confidence: 89%

“…SARS‐CoV‐2 RNA detected by ISH was measured as previously described (Mulka et al., 2021 ). In situ hybridization (ISH) was performed on sections (5 mm thick) of formalin‐fixed lung mounted onto charged glass slides using the Leica Bond RX automated system (Leica Biosystems, Richmond, IL).…”

Section: Methodsmentioning

confidence: 99%

A bacterial extracellular vesicle‐based intranasal vaccine against SARS‐CoV‐2 protects against disease and elicits neutralizing antibodies to wild‐type and Delta variants

Jiang

Driedonks

Jong

et al. 2022

J of Extracellular Vesicle

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Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, wellcharacterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titres of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. UponThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…We report that this technology efficiently couples a SpyTag-RBD fusion protein produced in mammalian cell culture onto bacterial OMVs, resulting in RBD-OMVs that are recognized by antibodies against SARS-CoV-2. Furthermore, we show that intranasal vaccination with RBD-OMVs elicits antibodies, including neutralization responses against both wildtype and Delta viral variants, and confers protection against challenge with SARS-CoV-2 in a recently developed hamster model 18,19 .…”

Section: Introductionmentioning

confidence: 89%

“…SARS-CoV-2 RNA detected by ISH was measured as previously described 19 . In situ hybridization (ISH) was performed on sections (5 mm thick) of formalin-fixed lung mounted onto charged glass slides using the Leica Bond RX automated system (Leica Biosystems, Richmond, IL).…”

Section: Rna-in Situ Hybridization (Rna-ish)mentioning

confidence: 99%

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants

Jiang

Lowman

Jong

et al. 2021

Preprint

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Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, and emergence of SARS-CoV-2 variants or entirely new viruses. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titers of blood anti-RBD IgG as well as detectable mucosal responses. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided weight loss, had lower virus titers in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.

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Progression and Resolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Golden Syrian Hamsters

Cited by 25 publications

References 42 publications

Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune sera: Quantitative image analysis in pathologic assessments

Reduced SARS-CoV-2 disease outcomes in Syrian hamsters receiving immune sera: Quantitative image analysis in pathologic assessments

A bacterial extracellular vesicle‐based intranasal vaccine against SARS‐CoV‐2 protects against disease and elicits neutralizing antibodies to wild‐type and Delta variants

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants

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