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Article ; Online: Mucosal vaccine-induced cross-reactive CD8

Ying, Baoling / Darling, Tamarand L / Desai, Pritesh / Liang, Chieh-Yu / Dmitriev, Igor P / Soudani, Nadia / Bricker, Traci / Kashentseva, Elena A / Harastani, Houda / Raju, Saravanan / Liu, Meizi / Schmidt, Aaron G / Curiel, David T / Boon, Adrianus C M / Diamond, Michael S

Nature immunology

2024 Volume 25, Issue 3, Page(s) 537–551

Abstract: A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which ... ...

Abstract	A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced by monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect in passive transfer experiments, mucosal antibody and cross-reactive memory T cell responses were robust, and protection was evident against WA1/2020 D614G and Omicron variants BQ.1.1 and XBB.1.5 in mice and hamsters. However, depletion of memory CD8
MeSH term(s)	Cricetinae ; Animals ; Mice ; CD8-Positive T-Lymphocytes ; SARS-CoV-2 ; COVID-19/prevention & control ; Respiratory Tract Infections ; Vaccines ; Antibodies, Neutralizing ; Broadly Neutralizing Antibodies ; Pan troglodytes
Chemical Substances	Vaccines ; Antibodies, Neutralizing ; Broadly Neutralizing Antibodies
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-024-01743-x
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Article ; Online: Author Correction: Mucosal vaccine-induced cross-reactive CD8

Nature immunology

2024 Volume 25, Issue 3, Page(s) 578

Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Published Erratum
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-024-01781-5
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Article: A bivalent ChAd nasal vaccine protects against SARS-CoV-2 BQ.1.1 and XBB.1.5 infection and disease in mice and hamsters.

Ying, Baoling / Darling, Tamarand L / Desai, Pritesh / Liang, Chieh-Yu / Dmitriev, Igor P / Soudani, Nadia / Bricker, Traci / Kashentseva, Elena A / Harastani, Houda / Schmidt, Aaron G / Curiel, David T / Boon, Adrianus C M / Diamond, Michael S

bioRxiv : the preprint server for biology

2023

Abstract: We previously described a nasally delivered monovalent adenoviral-vectored SARS-CoV-2 vaccine (ChAd-SARS-CoV-2-S, targeting Wuhan-1 spike [S]; ... ...

Abstract	We previously described a nasally delivered monovalent adenoviral-vectored SARS-CoV-2 vaccine (ChAd-SARS-CoV-2-S, targeting Wuhan-1 spike [S]; iNCOVACC
Language	English
Publishing date	2023-05-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.05.04.539332
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Article: Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron Variants in Mice and Hamsters.

Case, James Brett / Scheaffer, Suzanne M / Darling, Tamarand L / Bricker, Traci L / Adams, Lucas J / Harastani, Houda / Trende, Reed / Sanapala, Shilpa / Fremont, Daved H / Boon, Adrianus C M / Diamond, Michael S

bioRxiv : the preprint server for biology

2023

Abstract: The continued evolution and emergence of novel SARS-CoV-2 variants has resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure ... ...

Abstract	The continued evolution and emergence of novel SARS-CoV-2 variants has resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure testing. Here, we tested a currently circulating SARS-CoV-2 Omicron lineage variant, BQ.1.1, in multiple rodent models including K18-hACE2 transgenic, C57BL/6J, and 129S2 mice, and Syrian golden hamsters. In contrast to a previously dominant BA.5.5 Omicron variant, inoculation of K18-hACE2 mice with BQ.1.1 resulted in a substantial weight loss, a characteristic seen in pre-Omicron variants. BQ.1.1 also replicated to higher levels in the lungs of K18-hACE2 mice and caused greater lung pathology than the BA.5.5 variant. However, C57BL/6J mice, 129S2 mice, and Syrian hamsters inoculated with BQ.1.1 showed no differences in respiratory tract infection or disease compared to animals administered BA.5.5. Airborne or direct contact transmission in hamsters was observed more frequently after BQ.1.1 than BA.5.5 infection. Together, these data suggest that the BQ.1.1 Omicron variant has increased virulence in some rodent species, possibly due to the acquisition of unique spike mutations relative to other Omicron variants. Importance: As SARS-CoV-2 continues to evolve, there is a need to rapidly assess the efficacy of vaccines and antiviral therapeutics against newly emergent variants. To do so, the commonly used animal models must also be reevaluated. Here, we determined the pathogenicity of the circulating BQ.1.1 SARS-CoV-2 variant in multiple SARS-CoV-2 animal models including transgenic mice expressing human ACE2, two strains of conventional laboratory mice, and Syrian hamsters. While BQ.1.1 infection resulted in similar levels of viral burden and clinical disease in the conventional laboratory mice tested, increases in lung infection were detected in human ACE2-expressing transgenic mice, which corresponded with greater levels of pro-inflammatory cytokines and lung pathology. Moreover, we observed a trend towards greater animal-to-animal transmission of BQ.1.1 than BA.5.5 in Syrian hamsters. Together, our data highlight important differences in two closely related Omicron SARS-CoV-2 variant strains and provide a foundation for evaluating countermeasures.
Language	English
Publishing date	2023-05-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.28.538747
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: mRNA Vaccine Mitigates SARS-CoV-2 Infections and COVID-19.

Kackos, Christina M / Surman, Sherri L / Jones, Bart G / Sealy, Robert E / Jeevan, Trushar / Davitt, Christopher J H / Pustylnikov, Sergei / Darling, Tamarand L / Boon, Adrianus C M / Hurwitz, Julia L / Samsa, Marcelo M / Webby, Richard J

Microbiology spectrum

2023 Volume 11, Issue 1, Page(s) e0424022

Abstract: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in December of 2019 and is responsible for millions of infections and deaths across the globe. Vaccination against SARS-CoV-2 has proven effective to ... ...

Abstract	The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in December of 2019 and is responsible for millions of infections and deaths across the globe. Vaccination against SARS-CoV-2 has proven effective to contain the spread of the virus and reduce disease. The production and distribution of these vaccines occurred at a remarkable pace, largely through the employment of the novel mRNA platform. However, interruptions in supply chain and high demand for clinical grade reagents have impeded the manufacture and distribution of mRNA vaccines at a time when accelerated vaccine deployment is crucial. Furthermore, the emergence of SARS-CoV-2 variants across the globe continues to threaten the efficacy of vaccines encoding the ancestral virus spike protein. Here, we report results from preclinical studies on mRNA vaccines developed using a proprietary mRNA production process developed by GreenLight Biosciences. Two mRNA vaccines encoding the full-length, nonstabilized SARS-CoV-2 spike protein, GLB-COV2-042 and GLB-COV2-043, containing uridine and pseudouridine, respectively, were evaluated in rodents for their immunogenicity and protection from SARS-CoV-2 challenge with the ancestral strain and the Alpha (B.1.1.7) and Beta (B.1.351) variants. In mice and hamsters, both vaccines induced robust spike-specific binding and neutralizing antibodies, and in mice, vaccines induced significant T cell responses with a clear Th1 bias. In hamsters, both vaccines conferred significant protection following challenge with SARS-CoV-2 as assessed by weight loss, viral load, and virus replication in the lungs and nasopharynx. These results support the development of GLB-COV2-042 and GLB-COV2-043 for clinical use.
MeSH term(s)	Animals ; Cricetinae ; Humans ; Mice ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; mRNA Vaccines/immunology ; SARS-CoV-2/genetics
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; mRNA Vaccines ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-01-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.04240-22
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Article ; Online: Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron variants in mice and hamsters.

Case, James Brett / Scheaffer, Suzanne M / Darling, Tamarand L / Bricker, Traci L / Adams, Lucas J / Harastani, Houda H / Trende, Reed / Sanapala, Shilpa / Fremont, Daved H / Boon, Adrianus C M / Diamond, Michael S

Journal of virology

2023 Volume 97, Issue 9, Page(s) e0062823

Abstract: The continued evolution and emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and ... ...

Abstract	The continued evolution and emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure testing. Here, we tested a recently circulating SARS-CoV-2 Omicron lineage variant, BQ.1.1, in multiple rodent models including K18-human ACE2 (hACE2) transgenic, C57BL/6J, and 129S2 mice, and Syrian golden hamsters. In contrast to a previously dominant BA.5.5 Omicron variant, inoculation of K18-hACE2 mice with BQ.1.1 resulted in substantial weight loss, a characteristic seen in pre-Omicron variants. BQ.1.1 also replicated to higher levels in the lungs of K18-hACE2 mice and caused greater lung pathology than the BA.5.5 variant. However, in C57BL/6J mice, 129S2 mice, and Syrian hamsters, BQ.1.1 did not cause increased respiratory tract infection or disease compared to animals administered BA.5.5. Moreover, the rates of direct contact or airborne transmission in hamsters were not significantly different after BQ.1.1 and BA.5.5 infections. Taken together, these data suggest that the BQ.1.1 Omicron variant has increased virulence in rodent species that express hACE2, possibly due to the acquisition of unique spike mutations relative to earlier Omicron variants. IMPORTANCE As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, there is a need to rapidly assess the efficacy of vaccines and antiviral therapeutics against newly emergent variants. To do so, the commonly used animal models must also be re-evaluated. Here, we determined the pathogenicity of the BQ.1.1 SARS-CoV-2 variant in multiple SARS-CoV-2 animal models including transgenic mice expressing human ACE2 (hACE2), two strains of conventional laboratory mice, and Syrian hamsters. While BQ.1.1 and BA.5.5 infection resulted in similar levels of viral burden and clinical disease in hamsters and the conventional strains of laboratory mice tested, increases in lung infection were detected in hACE2-expressing transgenic mice, which corresponded with greater levels of pro-inflammatory cytokines and lung pathology. Taken together, our data highlight important differences in two closely related Omicron SARS-CoV-2 variant strains and provide a foundation for evaluating countermeasures.
MeSH term(s)	Animals ; Cricetinae ; Humans ; Mice ; COVID-19/virology ; Disease Models, Animal ; Lung/pathology ; Lung/virology ; Mesocricetus/virology ; Mice, Inbred C57BL ; Mice, Transgenic ; SARS-CoV-2/classification ; SARS-CoV-2/genetics ; SARS-CoV-2/pathogenicity ; Viral Load ; Virulence
Chemical Substances	ACE2 protein, human (EC 3.4.17.23) ; spike protein, SARS-CoV-2
Language	English
Publishing date	2023-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00628-23
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Article: The highly conserved stem-loop II motif is dispensable for SARS-CoV-2.

Jiang, Hongbing / Joshi, Astha / Gan, Tianyu / Janowski, Andrew B / Fujii, Chika / Bricker, Traci L / Darling, Tamarand L / Harastani, Houda H / Seehra, Kuljeet / Chen, Hongwei / Tahan, Stephen / Jung, Ana / Febles, Binita / Blatter, Joshua A / Handley, Scott A / Parikh, Bijal A / Wang, David / Boon, Adrianus Cm

bioRxiv : the preprint server for biology

2023

Abstract: The stem-loop II motif (s2m) is a RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ... ...

Abstract	The stem-loop II motif (s2m) is a RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over twenty-five years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth Importance: RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contain functional structures to support virus replication, translation and evasion of the host antiviral immune response. The 3' untranslated region of early isolates of SARS-CoV-2 contained a stem-loop II motif (s2m), which is a RNA structural element that is found in many RNA viruses. This motif was discovered over twenty-five years ago, but its functional significance is unknown. We created SARS-CoV-2 with deletions or mutations of the s2m and determined the effect of these changes on viral growth in tissue culture and in rodent models of infection. Deletion or mutation of the s2m element had no effect on growth
Language	English
Publishing date	2023-03-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.15.532878
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Article ; Online: The Highly Conserved Stem-Loop II Motif Is Dispensable for SARS-CoV-2.

Journal of virology

2023 Volume 97, Issue 6, Page(s) e0063523

Abstract: The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, ... ...

Abstract	The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth
MeSH term(s)	Animals ; Cricetinae ; 3' Untranslated Regions/genetics ; COVID-19/virology ; Mesocricetus ; Mutation ; SARS-CoV-2/genetics ; Nucleotide Motifs/genetics ; RNA, Viral/chemistry ; RNA, Viral/genetics
Chemical Substances	3' Untranslated Regions ; RNA, Viral
Language	English
Publishing date	2023-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00635-23
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Reduced airborne transmission of SARS-CoV-2 BA.1 Omicron virus in Syrian hamsters.

Boon, Adrianus C M / Darling, Tamarand L / Halfmann, Peter J / Franks, John / Webby, Richard J / Barouch, Dan H / Port, Julia R / Munster, Vincent J / Diamond, Michael S / Kawaoka, Yoshihiro

PLoS pathogens

2022 Volume 18, Issue 12, Page(s) e1010970

MeSH term(s)	Animals ; Cricetinae ; Mesocricetus ; SARS-CoV-2 ; Respiratory Aerosols and Droplets ; COVID-19
Language	English
Publishing date	2022-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010970
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Article ; Online: Characterization of the SARS-CoV-2 BA.5.5 and BQ.1.1 Omicron Variants in Mice and Hamsters

Case, James Brett / Scheaffer, Suzanne M / Darling, Tamarand L / Bricker, Traci L / Adams, Lucas J / Harastani, Houda H. / Trende, Reed / Sanapala, Shilpa / Fremont, Daved H / Boon, Adrianus C M / Diamond, Michael S

bioRxiv

Abstract	The continued evolution and emergence of novel SARS-CoV-2 variants has resulted in challenges to vaccine and antibody efficacy. The emergence of each new variant necessitates the need to re-evaluate and refine animal models used for countermeasure testing. Here, we tested a currently circulating SARS-CoV-2 Omicron lineage variant, BQ.1.1, in multiple rodent models including K18-hACE2 transgenic, C57BL/6J, and 129S2 mice, and Syrian golden hamsters. In contrast to a previously dominant BA.5.5 Omicron variant, inoculation of K18-hACE2 mice with BQ.1.1 resulted in a substantial weight loss, a characteristic seen in pre-Omicron variants. BQ.1.1 also replicated to higher levels in the lungs of K18-hACE2 mice and caused greater lung pathology than the BA.5.5 variant. However, C57BL/6J mice, 129S2 mice, and Syrian hamsters inoculated with BQ.1.1 showed no differences in respiratory tract infection or disease compared to animals administered BA.5.5. Airborne or direct contact transmission in hamsters was observed more frequently after BQ.1.1 than BA.5.5 infection. Together, these data suggest that the BQ.1.1 Omicron variant has increased virulence in some rodent species, possibly due to the acquisition of unique spike mutations relative to other Omicron variants.
Keywords	covid19
Language	English
Publishing date	2023-05-01
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2023.04.28.538747
Database	COVID19

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