Early type I IFN blockade improves the efficacy of viral vaccines

Palacio, Nicole; Dangi, Tanushree; Chung, Young Rock; Wang, Yidan; Loredo-Varela, Juan Luis; Zhang, Zhongyao; Penaloza-MacMaster, Pablo

doi:10.1084/jem.20191220

Cited by 51 publications

(59 citation statements)

References 65 publications

(87 reference statements)

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“…Some CCHFV experimental vaccines have shown efficacy in type I IFN-deficient mice after a single-dose 13,20,21 . However, our immunogenicity data certainly indicate that the third vaccination may not be needed and the use of immunodeficient mice may not strictly predict efficacy in immunocompetent non-human primates and humans 43,44 . Second, our study design of performing a timed necropsy on day 6 PI was chosen to maximize readout parameters but it prevented us from evaluating the possibility of delayed disease development in sham and NP + GPC vaccinated animals.…”

Section: Discussionmentioning

confidence: 95%

A DNA-based vaccine protects against Crimean-Congo haemorrhagic fever virus disease in a Cynomolgus macaque model

et al. 2020

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There is currently no specific prophylaxis or vaccine against Crimean-Congo haemorrhagic fever virus (CCHFV). Crimean-Congo haemorrhagic fever (CCHF) is a severe febrile illness transmitted by Hyalomma ticks in endemic areas, handling of infected livestock or care of infected patients. We report here the successful protection against CCHFV-mediated disease in a non-human primate disease model. Cynomolgus macaques were vaccinated with a DNA-based vaccine using in vivo electroporation-assisted delivery. The vaccine contained two plasmids encoding the glycoprotein precursor (GPC) and the nucleoprotein (NP) of CCHFV. Animals received three vaccinations and we recorded potent antibody and T cell responses after vaccination. While all sham-vaccinated animals developed viraemia, high tissue viral loads and CCHF-induced disease, the NP + GPC vaccinated animals were significantly protected. In conclusion, this is evidence of a vaccine that can protect against CCHFV-induced disease in a non-human primate model. This supports clinical development of the vaccine to protect groups at risk for contracting the infection.

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Section: Discussionmentioning

confidence: 95%

A DNA-based vaccine protects against Crimean-Congo haemorrhagic fever virus disease in a Cynomolgus macaque model

et al. 2020

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“…This earlier study showed that CD8 T cells primed at the early stage of the infection preferentially differentiate into Tem, whereas CD8 T cells primed during the end of the infection preferentially differentiate into Tcm. Furthermore, we have previously shown that protracted acute infections favor Tem differentiation ( 13 ). Altogether, these prior reports suggest that a protracted antigen stimulation after a prime imprints a Tem phenotype, whereas a shortened antigen stimulation after a prime imprints a Tcm phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…Binding antibody titers were measured using ELISA as described previously ( 18 , 19 ), but using spike protein instead of viral lysates. In brief, 96-well flat bottom plates MaxiSorp (Thermo Scientific) were coated with 0.1μg/well of the respective spike protein, for 48 hr at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Limiting the priming dose of a SARS CoV-2 vaccine improves virus-specific immunity

Sanchez

Palacio

Dangi

et al. 2021

Preprint

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Since late 2019, SARS-CoV-2 has caused a global pandemic that has infected 128 million people worldwide. Although several vaccine candidates have received emergency use authorization (EUA), there are still a limited number of vaccine doses available. To increase the number of vaccinated individuals, there are ongoing discussions about administering partial vaccine doses, but there is still a paucity of data on how vaccine fractionation affects vaccine-elicited immunity. We performed studies in mice to understand how the priming dose of a SARS CoV-2 vaccine affects long-term immunity to SARS CoV-2. We first primed C57BL/6 mice with an adenovirus-based vaccine encoding SARS CoV-2 spike protein (Ad5-SARS-2 spike), similar to that used in the CanSino and Sputnik V vaccines. This prime was administered either at a low dose (LD) of 106 PFU or at a standard dose (SD) of 109 PFU, followed by a SD boost in all mice four weeks later. As expected, the LD prime induced lower immune responses relative to the SD prime. However, the LD prime elicited immune responses that were qualitatively superior, and upon boosting, mice that were initially primed with a LD exhibited significantly more potent immune responses. Overall, these data demonstrate that limiting the priming dose of a SARS CoV-2 vaccine may confer unexpected benefits. These findings may be useful for improving vaccine availability and for rational vaccine design.

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“…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

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Dangi

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.

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Early type I IFN blockade improves the efficacy of viral vaccines

Cited by 51 publications

References 65 publications

A DNA-based vaccine protects against Crimean-Congo haemorrhagic fever virus disease in a Cynomolgus macaque model

A DNA-based vaccine protects against Crimean-Congo haemorrhagic fever virus disease in a Cynomolgus macaque model

Limiting the priming dose of a SARS CoV-2 vaccine improves virus-specific immunity

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

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