SARS-CoV-2 vaccines in development

Krammer, Florian

doi:10.1038/s41586-020-2798-3

Cited by 1,792 publications

(1,766 citation statements)

References 98 publications

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“…Based on the uncertainty of whether cross-reactive T cells or antibodies will provide protective or long-lasting immunity to COVID-19, it will become absolutely critical to administrate a safe and effective vaccine to the population to reach broad immunity and break the negative spiral of new infections. Ongoing vaccine efforts mainly target B cells to promote the induction of neutralizing antibodies (nAbs) against SARS-CoV-2 (53,54). Although the induction of anti-spike nAbs is the key component for an effective SARS-CoV-2 vaccine, it is well-known that T cells, and in particular TFH cells, are critical to generate antibody-producing plasma cells and long-lived memory B cells.…”

Section: T Cells In Vaccinesmentioning

confidence: 99%

The known unknowns of T cell immunity to COVID-19

2020

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Section: T Cells In Vaccinesmentioning

confidence: 99%

The known unknowns of T cell immunity to COVID-19

2020

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“…Major efforts are underway to develop safe and effective drugs to treat COVID-19: Preventive and therapeutic strategies currently being explored include vaccination, SARS-CoV-2-specific antibodies, novel nucleoside analogs such as remdesivir, and repurposed drugs [23,24]. Remdesivir, an agent originally developed for treatment of Ebola virus, was reported to shorten the time to recovery in adults who were hospitalized with COVID-19 [25]; yet, a 10-day course of remdesivir did not show a statistically significant difference in clinical status compared with standard care for patients with moderate COVID-19 [26].…”

Section: Introductionmentioning

confidence: 99%

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19

et al. 2020

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The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of coexisting medical conditions, while the underlying mechanisms remain unclear. Furthermore, there are no approved therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, disease manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus–host protein–protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measurement revealed underlying pathogenesis for broad COVID-19-associated disease manifestations. Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2). To prioritize potential treatments, we combined network-based prediction and a propensity score (PS) matching observational study of 26,779 individuals from a COVID-19 registry. We identified that melatonin usage (odds ratio [OR] = 0.72, 95% CI 0.56–0.91) is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2 confirmed by reverse transcription–polymerase chain reaction assay. Using a PS matching user active comparator design, we determined that melatonin usage was associated with a reduced likelihood of SARS-CoV-2 positive test result compared to use of angiotensin II receptor blockers (OR = 0.70, 95% CI 0.54–0.92) or angiotensin-converting enzyme inhibitors (OR = 0.69, 95% CI 0.52–0.90). Importantly, melatonin usage (OR = 0.48, 95% CI 0.31–0.75) is associated with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2 in African Americans after adjusting for age, sex, race, smoking history, and various disease comorbidities using PS matching. In summary, this study presents an integrative network medicine platform for predicting disease manifestations associated with COVID-19 and identifying melatonin for potential prevention and treatment of COVID-19.

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“…Наибольшее количество их приходится опять-таки на аденовирусный вектор ChАдY25, а наименьшее -на HАд26, и, следовательно, с первым вектором связан наибольший, а со вторым -наименьший риск возникновения осложнений с дизрегуляцией иммунной системы. В этой связи нельзя не упомянуть о худшем профиле безопасности при клинических испытаниях вакцины СhAdOx 1nCov-19, чем у использованной в качестве плацебо одной из лицензированных противоменингитных вакцин, независимо от того, применялся или нет парацетамол для облегчения побочных эффектов [12]. Трудно признать случайным параллелизм в возникновении у двух привитых вакциной СhAdOx1 nCov-19 волонтеров неврологических осложнений и в целом худшего у этой вакцины профиля безопасности по сравнению с плацебо.…”

Section: результаты и обсуждениеunclassified

Vaccines against Covid-19: the Comparative Estimates of Risks in Adenovirus Vectors

Kharchenko

2020

Epidemiology and Vaccinal Prevention

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Relevance. The vaccine against the SARS-Cov-2 coronavirus is considered as the most promising approach to curb (tame) a current pandemic and prevent new one. Three vaccines (AstraZeneca’s СhAdOx1 nCov-19, CanSino’s vaccine and Russia’s Sputnik V one) are in Phase III clinical trials and have the S protein as immunogen but different adenovirus vectors. It is known adverse neurological events associated with the СhAdOx1 nCov-19 vacсine.Aim is to investigate the distribution of homologous sequences of adenovirus proteins in human nervous and immune systems proteins, estimate potential risks of using adenovirus vectors in vaccines and discuss possible mechanisms inducing immune damage in the nervous system.Materials and methods. For the computer analysis of peptide (immune epitope) relationship between adenovirus structural proteins and human proteins, the search of homologous sequences was made. All protein sequences were used from databases available on the INTERNET.Results. Among adenoviruses (НАд5, НАд26 , ChАдY25, and SAd3) ChАдY25 has the highest content of sequences homologous to human nervous system proteins that may be the cause of autoimmune complications in vaccination.Conclusion: In AstraZeneca’s СhAdOx1 nCov-19 vaccine there are a large number of peptide sequences homologous to human nervous system proteins and it allows to predict the possible risks with this vaccine.

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SARS-CoV-2 vaccines in development

Cited by 1,792 publications

References 98 publications

The known unknowns of T cell immunity to COVID-19

The known unknowns of T cell immunity to COVID-19

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19

Vaccines against Covid-19: the Comparative Estimates of Risks in Adenovirus Vectors

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