Cutting Edge: Mouse SARS-CoV-2 Epitope Reveals Infection and Vaccine-Elicited CD8 T Cell Responses

Joag, Vineet; Wijeyesinghe, Sathi; Stolley, J. Michael; Quarnstrom, Clare F.; Dileepan, Thamotharampillai; Soerens, Andrew G.; Sangala, Jules; O’Flanagan, Stephen; Gavil, Noah Veis; Hong, Sung Wook; Bhela, Siddheshvar; Gangadhara, Sailaja; Weyu, Eyob; Matchett, William E.; Thiede, Joshua M.; Krishna, Venkatramana D.; Cheeran, Maxim C.-J.; Bold, Tyler D.; Amara, Rama Rao; Southern, Peter J.; Hart, Geoffrey T.; Schifanella, Luca; Vezys, Vaiva; Jenkins, Marc K.; Langlois, Ryan A.; Masopust, David

doi:10.4049/jimmunol.2001400

Cited by 39 publications

(41 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we focus on a specific topic: our current knowledge concerning the definition and recognition of SARS-CoV-2-derived T cell epitopes in humans. While the data related to this topic was initially sparse, 25 different studies have now been published as of March 15, 2021 (Chen et al, 2021;Ferretti et al, 2020;Gangaev et al, 2020;Habel et al, 2020;Joag et al, 2021;Kared et al, 2021;Keller et al, 2020;Le Bert et al, 2021Lee et al, 2020;Mahajan et al, 2020;Mateus et al, 2020;Nelde et al, 2021;Nielsen et al, 2020;Peng et al, 2020;Poran et al, 2020bPoran et al, , 2020aPrakash et al, 2020;Rha et al, 2021;Sahin et al, 2020;Saini et al, 2020, 2021, Schulien et al, 2021Sekine et al, 2020;Shomuradova et al, 2020;Snyder et al, 2020;Tarke et al, 2021a), which collectively report data from 1,197 human subjects (870 COVID-19 and 327 unexposed controls), leading to the identification of over 1,400 different CD4 (n = 382) and CD8 (n = 1052) T cell epitopes. These studies are listed in Table 1, which also captures whether these studies defined class I/CD8 epitopes and/or class II/CD4 epitopes.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19

Grifoni

Sidney

Vita

et al. 2021

Cell Host & Microbe

269

View full text Add to dashboard Cite

Over the past year, numerous studies in the peer reviewed and preprint literature have reported on the virological, epidemiological and clinical characteristics of the coronavirus, SARS-CoV-2. To date, 25 studies have investigated and identified SARS-CoV-2-derived T cell epitopes in humans. Here, we review these recent studies, how they were performed, and their findings. We review how epitopes identified throughout the SARS-CoV2 proteome reveal significant correlation between number of epitopes defined and size of the antigen provenance. We also report additional analysis of SARS-CoV-2 human CD4 and CD8 T-cell epitope data compiled from these studies, identifying 1400 different reported SARS-CoV-2 epitopes and revealing discrete immunodominant regions of the virus and epitopes that are more prevalently recognized. This remarkable breadth of epitope repertoire has implications for vaccine design, cross-reactivity and for immune escape by SARS-CoV-2 variants.

show abstract

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19

Grifoni

Sidney

Vita

et al. 2021

Cell Host & Microbe

269

View full text Add to dashboard Cite

show abstract

“…dose of 1.8 Â 10 11 viral particles of either a replication-deficient (E1-and E3-deleted) human adenovirus type 5 (Ad5) vectors expressing SARS-CoV-2-N (Ad5-N) or a control Ad-5 vector (Ad5-NULL). Ad5 vectors were constructed as described (6). Hamsters were moved to BSL-3 containment for SARS-CoV-2 challenge studies, anesthetized with isoflurane and challenged intranasally (i.n.)…”

Section: Hamster Immunizations and Sars-cov-2 Infectionmentioning

confidence: 99%

“…1A, 1B). Vaccinated hamsters were also challenged with WA or a variant strain B.1.1.7, which contains two amino acid substitutions in N that do not occur within the N 219227 immunodominant epitope that we previously defined in C57BL/6 mice (6). Vaccination elicited a significant 30-fold (WA) and 12-fold (B.1.1.7) reduction in median lung viral titer 3 days following challenge, although the latter was not significant.…”

Section: Ad5-n Vaccine Confers Protection Against Sars-cov-2 Infectionmentioning

confidence: 99%

Cutting Edge: Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity

Matchett

Joag

Stolley

et al. 2021

The Journal of Immunology

Self Cite

139

117

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Neutralizing Abs target the receptor binding domain of the spike (S) protein, a focus of successful vaccine efforts. Concerns have arisen that S-specific vaccine immunity may fail to neutralize emerging variants. We show that vaccination with a human adenovirus type 5 vector expressing the SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity, defined by reduced weight loss and viral load, in both Syrian hamsters and K18-hACE2 mice. Challenge of vaccinated mice was associated with rapid N-specific T cell recall responses in the respiratory mucosa. This study supports the rationale for including additional viral Ags in SARS-CoV-2 vaccines, even if they are not a target of neutralizing Abs, to broaden epitope coverage and immune effector mechanisms.

show abstract

“…Mice were immunized intramuscularly (50 μL per quadriceps) with an Ad5 vector expressing SARS CoV-2 spike protein (Ad5-S), or nucleocapsid protein (Ad5-N), or both; diluted in sterile PBS, at 10 9 PFU per mouse. Ad5-N was a kind gift of the Masopust/Vezys laboratory 32 . These are non-replicating Ad5 vectors (E1/E3 deleted).…”

Section: Methodsmentioning

confidence: 99%

A SARS CoV-2 nucleocapsid vaccine protects against distal viral dissemination

Class

Dangi

Richner

et al. 2021

Preprint

View full text Add to dashboard Cite

The SARS CoV-2 pandemic has killed millions of people. This viral infection can also result in substantial morbidity, including respiratory insufficiency and neurological manifestations, such as loss of smell and psychiatric diseases. Most SARS CoV-2 vaccines are based on the spike antigen, and although they have shown extraordinary efficacy at preventing severe lung disease and death, they do not always confer sterilizing immune protection. We performed studies in K18-hACE2 mice to evaluate whether the efficacy of SARS CoV-2 vaccines could be augmented by incorporating nucleocapsid as a vaccine antigen. We vaccinated mice with adenovirus-based vaccines encoding spike antigen alone, nucleocapsid antigen alone, or combined spike and nucleocapsid antigens. Mice were then challenged intranasally with SARS CoV-2, and acute viral loads were quantified at a proximal site of infection (lung) and a distal site of infection (brain). Interestingly, the spike-based vaccine conferred acute protection in the lung, but not in the brain. The spike-based vaccine conferred acute protection in the brain only if combined with the nucleocapsid-based vaccine. These findings suggest that nucleocapsid-specific immunity is important for the distal control of SARS CoV-2, warranting the inclusion of nucleocapsid in next-generation COVID-19 vaccines.

show abstract

Cutting Edge: Mouse SARS-CoV-2 Epitope Reveals Infection and Vaccine-Elicited CD8 T Cell Responses

Cited by 39 publications

References 20 publications

SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19

SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19

Cutting Edge: Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity

A SARS CoV-2 nucleocapsid vaccine protects against distal viral dissemination

Contact Info

Product

Resources

About