Protection against SARS-CoV-2 infection by a mucosal vaccine in rhesus macaques

Sui, Yongjun; Li, Jianping; Zhang, Roushu; Prabhu, Sunaina Kiran; Andersen, Hanné; Venzon, David; Cook, Anthony; Brown, Renita; Teow, Elyse; Velasco, Jason; Greenhouse, Jack; Putman-Taylor, Tammy; Campbell, Tracey-Ann; Pessaint, Laurent; Moore, Ian N.; Lagenaur, Laurel A.; Talton, James D.; Breed, Matthew W.; Kramer, Josh; Bock, Kevin W.; Minai, Mahnaz; Nagata, Bianca M.; Lewis, Mark G.; Wang, Lai-Xi; Berzofsky, Jay A.

doi:10.1172/jci.insight.148494

Cited by 56 publications

(67 citation statements)

References 53 publications

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“…Several important studies for understanding SARS-CoV-2 pathogenesis and transmission dynamics and assessing the efficacy of vaccines and therapeutics have been conducted in clinically relevant non-human primate (NHP) models, such as rhesus macaques, cynomolgus monkeys, and African green monkeys [81][82][83][84][85][86][87][88]. These models have distinct advantages over human subjects, including ease of control over experimental variables and ability for repeated sampling, among others [89,90].…”

Section: Utility In Clinical and Research Settingsmentioning

confidence: 99%

SARS-CoV-2 Subgenomic RNAs: Characterization, Utility, and Perspectives

Long

2021

Viruses

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SARS-CoV-2, the etiologic agent at the root of the ongoing COVID-19 pandemic, harbors a large RNA genome from which a tiered ensemble of subgenomic RNAs (sgRNAs) is generated. Comprehensive definition and investigation of these RNA products are important for understanding SARS-CoV-2 pathogenesis. This review summarizes the recent progress on SARS-CoV-2 sgRNA identification, characterization, and application as a viral replication marker. The significance of these findings and potential future research areas of interest are discussed.

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Section: Utility In Clinical and Research Settingsmentioning

confidence: 99%

SARS-CoV-2 Subgenomic RNAs: Characterization, Utility, and Perspectives

Long

2021

Viruses

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“…In all instances, both vaccinations have been shown to protect against respiratory SARS-CoV-2 exposure. 46 …”

Section: Intranasal Covid-19 Vaccinesmentioning

confidence: 99%

COVID-19 intranasal vaccines: current progress, advantages, prospects, and challenges

Dhama

Dhawan

Tiwari

et al. 2022

Human Vaccines & Immunotherapeutics

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Multiple vaccines have recently been developed, and almost all the countries are presently vaccinating their population to tackle the COVID-19 pandemic. Most of the COVID-19 vaccines in use are administered via intramuscular (IM) injection, eliciting protective humor and cellular immunity. COVID-19 intranasal (IN) vaccines are also being developed that have shown promising ability to induce a significant amount of antibody-mediated immune response and a robust cell-mediated immunity as well as hold the added ability to stimulate protective mucosal immunity along with the additional advantage of the ease of administration as compared to IM injected vaccines. By inducing secretory IgA antibody responses specifically in the nasal compartment, the intranasal SARS-CoV-2 vaccine can prevent virus infection, replication, shedding, and disease development, as well as possibly limits virus transmission. This article highlights the current progress, advantages, prospects, and challenges in developing intranasal COVID-19 vaccines for countering the ongoing pandemic.

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“…To evaluate the innate immunity induced by SARS-CoV-2 spike protein S1, we incubated the lung BAL cells with either 1 µg/ml (T1, 8.6nM) or 2 µg/ml (T2, 17.2nM) of S1 protein for hours. We chose these two concentrations of S1 protein based on that 1) as high as 28nM of S protein was added for in vitro stimulations in a SARS in vitro study (19); 2) In SARS-CoV-2 and HIV studies, 1-5ug/ml (8-40 nM) spike/envelope protein (peptide pool) is used to stimulate antigen-specific cells in vitro (20)(21)(22)(23)(24). This range is based on the viral load, and viral protein concentration in vivo.…”

Section: Sars-cov-2 Spike Protein Suppressed Ace2 and Type I Interferon Mrna Expression In Most Of The Primary Lung Bronchoalveolar Lavagmentioning

confidence: 99%

SARS-CoV-2 Spike Protein Suppresses ACE2 and Type I Interferon Expression in Primary Cells From Macaque Lung Bronchoalveolar Lavage

Sui

Venzon

et al. 2021

Front. Immunol.

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SARS-CoV-2 virus causes upper and lower respiratory diseases including pneumonia, and in some cases, leads to lethal pulmonary failure. Angiotensin converting enzyme-2 (ACE2), the receptor for cellular entry of SARS-CoV-2 virus, has been shown to protect against severe acute lung failure. Here, we provide evidence that SARS-CoV-2 spike protein S1 reduced the mRNA expression of ACE2 and type I interferons in primary cells of lung bronchoalveolar lavage (BAL) from naïve rhesus macaques. The expression levels of ACE2 and type I interferons were also found to be correlated with each other, consistent with the recent finding that ACE2 is an interferon-inducible gene. Furthermore, induction of ACE2 and type I interferons by poly I:C, an interferon inducer, was suppressed by S1 protein in primary cells of BAL. These observations suggest that the downregulation of ACE2 and type I interferons induced by S1 protein may directly contribute to SARS-CoV-2-associated lung diseases.

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Protection against SARS-CoV-2 infection by a mucosal vaccine in rhesus macaques

Cited by 56 publications

References 53 publications

SARS-CoV-2 Subgenomic RNAs: Characterization, Utility, and Perspectives

SARS-CoV-2 Subgenomic RNAs: Characterization, Utility, and Perspectives

COVID-19 intranasal vaccines: current progress, advantages, prospects, and challenges

SARS-CoV-2 Spike Protein Suppresses ACE2 and Type I Interferon Expression in Primary Cells From Macaque Lung Bronchoalveolar Lavage

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