Interrogating Adaptive Immunity Using LCMV

Palacio

Sanchez

et al. 2021

Preprint

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Although SARS-CoV-2 vaccines have shown efficacy against SARS-CoV-2, it is unclear if they can also protect against other coronaviruses that may infect humans in the future. Here, we show that SARS-CoV-2 vaccination in humans elicits cross-reactive antibodies against other coronaviruses. Our studies in mice demonstrate that SARS-CoV-2 vaccination protects against a common cold coronavirus, and that SARS-CoV-1 vaccination protects against SARS-CoV-2. Similarly, infection with a common cold coronavirus also conferred enhanced protection from subsequent infections with other coronaviruses. Mechanistically, both T cells and antibodies mediated cross-protection. This is the first direct demonstration that coronavirus-specific immunity can confer heterologous protection in vivo, providing a rationale for universal coronavirus vaccines.

Section: Methodsmentioning

confidence: 99%

SARS coronavirus vaccines protect against different coronaviruses

Palacio

Sanchez

et al. 2021

Preprint

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“…Quantification of LCMV on Vero E6 cell monolayers was done as described in prior publications ( Dangi et al, 2020 ; Wang et al, 2019 ). In brief, Vero E6 cells (ATCC) were grown on 6-well plates at 2 × 10 5 cells/ml.…”

Section: Methodsmentioning

confidence: 99%

“…Virus-specific ELISA Virus-specific ELISA was done as described in prior publications (Dangi et al, 2020;Wang et al, 2019). In brief, 96-well flatbottom plates (MaxiSorp; Thermo Scientific) were coated with 100 µl/well of the respective viral lysate (e.g., Zika, YFV-17D, VSV, and MHV) diluted 1:10 in PBS for 48 h at room temperature.…”

Section: Reagents Flow Cytometry and Equipmentmentioning

confidence: 99%

Early type I IFN blockade improves the efficacy of viral vaccines

Palacio

Journal of Experimental Medicine

Chung

et al. 2020

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Type I interferons (IFN-I) are a major antiviral defense and are critical for the activation of the adaptive immune system. However, early viral clearance by IFN-I could limit antigen availability, which could in turn impinge upon the priming of the adaptive immune system. In this study, we hypothesized that transient IFN-I blockade could increase antigen presentation after acute viral infection. To test this hypothesis, we infected mice with viruses coadministered with a single dose of IFN-I receptor–blocking antibody to induce a short-term blockade of the IFN-I pathway. This resulted in a transient “spike” in antigen levels, followed by rapid antigen clearance. Interestingly, short-term IFN-I blockade after coronavirus, flavivirus, rhabdovirus, or arenavirus infection induced a long-lasting enhancement of immunological memory that conferred improved protection upon subsequent reinfections. Short-term IFN-I blockade also improved the efficacy of viral vaccines. These findings demonstrate a novel mechanism by which IFN-I regulate immunological memory and provide insights for rational vaccine design.

“…Binding antibody titers were quantified using ELISA as described previously 33,34 , using spike protein as a coating antigen. In brief, 96-well flat bottom plates MaxiSorp (Thermo Scientific) were coated with 0.1μg/well of SARS CoV-2 RBD protein, for 48 hr at 4°C.…”

Section: Methodsmentioning

confidence: 99%

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

Class

Richner

et al. 2021

Preprint

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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.