Pub Med luetuimpia artikkeleita 10 listan ensimmäistä 17.7. 2020. rokoteuutiset päälimmäisinä

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 1 Tämä artikkeli kertoo mRNA-1273-rokotteesta, joka  sai aikaan anti-SARS-CoV-2 immuunivastetta kaikissa kokeeseen osallistuneissa. Kandidaattirokote mRNA-1273 on eräs lipidinanopartikkelin  sisään kapseloitu  nukleosidilla modifioitu  lähetti-RNA-pohjainen  rokote , jossa   SARS-CoV-2 viruksen  piikkiproteiini S  on stabiloitu prefuusiomuotoonsa.  Viruksen pintapiikki (Spike) on se, millä se koettaa tarttua isäntäsoluun ja  se on  välttämätön viruksen pääsylle solun sisään ja  tämän viruksen vastaisen rokotteen kehittelyssä  se on  ensisijalla. Artikkeli kertoo suoritetusta  I kliinisen vaiheen  kokeesta terveillä aikuisilla, jotta selvitetään   mRNA-1273:n turvallisuus ja immunogenisyys  Kyse on väliaikatiedotuksesta. 
 

• Conclusions: The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461). 

• DOI: 10.1056/NEJMoa2022483

An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

Jackson LA, Anderson EJ et a. .." The candidate vaccine mRNA-1273 is a lipid nanoparticle–encapsulated, nucleoside-modified messenger RNA (mRNA)–based vaccine that encodes the SARS-CoV-2 spike (S) glycoprotein stabilized in its prefusion conformation. The S glycoprotein mediates host cell attachment and is required for viral entry³; it is the primary vaccine target for many candidate SARS-CoV-2 vaccines.^4-7We conducted a first-in-human phase 1 clinical trial in healthy adults to evaluate the safety and immunogenicity of mRNA-1273. Here we report interim results of the trial"

2.

SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls.

Le Bert N, Tan AT, Kunasegaran K, Tham CYL, Hafezi M, Chia A, Chng MHY, Lin M, Tan N, Linster M, Chia WN, Chen MI, Wang LF, Ooi EE, Kalimuddin S, Tambyah PA, Low JG, Tan YJ, Bertoletti A. Nature. 2020 Jul 15. doi: 10.1038/s41586-020-2550-z. Online ahead of print. PMID: 32668444.

Abstract

Memory T cells induced by previous pathogens can shape the susceptibility to, and clinical severity of, subsequent infections¹. Little is known about the presence of pre-existing memory T cells in humans with the potential to recognize SARS-CoV-2. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in COVID-19 convalescents (n=36). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then showed that SARS-recovered patients (n=23) still possess long-lasting memory T cells reactive to SARS-NP 17 years after the 2003 outbreak, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we also frequently detected SARS-CoV-2 specific T cells in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=37). SARS-CoV-2 T cells in uninfected donors exhibited a different pattern of immunodominance, frequently targeting the ORF-1-coded proteins NSP7 and 13 as well as the NP structural protein. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to "common cold" human coronaviruses but conserved amongst animal betacoranaviruses. Thus, infection with betacoronaviruses induces multispecific and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing NP- and ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic.

3

Potently neutralizing and protective human antibodies against SARS-CoV-2.

Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schäfer A, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Martinez DR, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Shrihari S, Mueller BK, Meiler J, Chandrashekar A, Mercado NB, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, McCune BT, Keeler SP, Holtzman MJ, Barouch DH, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr. Nature. 2020 Jul 15. doi: 10.1038/s41586-020-2548-6.
 Online ahead of print. PMID: 32668443The COVID-19 pandemic is a major threat to global health¹ for which there are limited medical countermeasures^2,3. Moreover, we currently lack a thorough understanding of mechanisms of humoral immunity⁴. From a larger panel of human monoclonal antibodies (mAbs) targeting the spike (S) glycoprotein⁵, we identified several that exhibited potent neutralizing activity and fully blocked the receptor-binding domain of S (S_RBD) from interacting with human ACE2 (hACE2). Competition-binding, structural, and functional studies allowed clustering of the mAbs into classes recognizing distinct epitopes on the S_RBD as well as distinct conformational states of the S trimer. Potent neutralizing mAbs recognizing non-overlapping sites, COV2-2196 and COV2-2130, bound simultaneously to S and synergistically neutralized authentic SARS-CoV-2 virus. In two mouse models of SARS-CoV-2 infection, passive transfer of either COV2-2196 or COV2-2130 alone or a combination of both mAbs protected mice from weight loss and reduced viral burden and inflammation in the lung. In addition, passive transfer of each of two of the most potently ACE2 blocking mAbs (COV2-2196 or COV2-2381) as monotherapy protected rhesus macaques from SARS-CoV-2 infection. These results identify protective epitopes on S_RBD and provide a structure-based framework for rational vaccine design and the selection of robust immunotherapeutics.

4

A perspective on potential antibody-dependent enhancement of SARS-CoV-2.

Arvin AM, Fink K, Schmid MA, Cathcart A, Spreafico R, Havenar-Daughton C, Lanzavecchia A, Corti D, Virgin HW. Nature. 2020 Jul 13. doi: 10.1038/s41586-020-2538-8. Online ahead of print. PMID: 32659783    Review.The possibility of antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection have the theoretical potential to amplify viral infections or trigger immunopathology. Observations relevant to the risks of ADE of disease require careful review at this critical point in the SARS-CoV-2 pandemic. At present, no clinical findings, immunologic assays or biomarkers are known to differentiate any severe viral infection from immune-enhanced disease, whether by antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same, and designing animal models depends on understanding how antiviral host responses may become harmful in people. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, since we cannot predict ADE of disease reliably after either vaccination or treatment with antibodies, regardless of what virus is the causative agent, it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 disease move forward.

5

The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis.

Winkler ES, Shrihari S, Hykes BL Jr, Handley SA, Andhey PS, Huang YS, Swain A, Droit L, Chebrolu KK, Mack M, Vanlandingham DL, Thackray LB, Cella M, Colonna M, Artyomov MN, Stappenbeck TS, Diamond MS. Cell. 2020 Jul 8:S0092-8674(20)30806-0. doi: 10.1016/j.cell.2020.06.029. Online ahead of print. PMID: 32668198

6

The link between Vitamin D and Covid-19: distinguishing facts from fiction.

Bergman P. J Intern Med. 2020 Jul 11. doi: 10.1111/joim.13158. Online ahead of print. PMID: 32652766https://doi.org/10.1111/joim.13158

7

Extrapulmonary manifestations of COVID-19.

Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, Bikdeli B, Ahluwalia N, Ausiello JC, Wan EY, Freedberg DE, Kirtane AJ, Parikh SA, Maurer MS, Nordvig AS, Accili D, Bathon JM, Mohan S, Bauer KA, Leon MB, Krumholz HM, Uriel N, Mehra MR, Elkind MSV, Stone GW, Schwartz A, Ho DD, Bilezikian JP, Landry DW. Nat Med. 2020 Jul;26(7):1017-1032. doi: 10.1038/s41591-020-0968-3. Epub 2020 Jul 10. PMID: 32651579
  Review. Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.

8

Ageing hallmarks exhibit organ-specific temporal signatures.

Schaum N, Lehallier B, Hahn O, Pálovics R, Hosseinzadeh S, Lee SE, Sit R, Lee DP, Losada PM, Zardeneta ME, Fehlmann T, Webber JT, McGeever A, Calcuttawala K, Zhang H, Berdnik D, Mathur V, Tan W, Zee A, Tan M; Tabula Muris Consortium, Pisco AO, Karkanias J, Neff NF, Keller A, Darmanis S, Quake SR, Wyss-Coray T. Nature. 2020 Jul 15. doi: 10.1038/s41586-020-2499-y. Online ahead of print. PMID: 32669715

9

Next-Generation Sequencing of T and B Cell Receptor Repertoires from COVID-19 Patients Showed Signatures Associated with Severity of Disease.

Schultheiß C, Paschold L, Simnica D, Mohme M, Willscher E, von Wenserski L, Scholz R, Wieters I, Dahlke C, Tolosa E, Sedding DG, Ciesek S, Addo M, Binder M. Immunity. 2020 Jun 30:S1074-7613(20)30279-X. doi: 10.1016/j.immuni.2020.06.024. Online ahead of print. PMID: 32668194 Free PMC article.

10

Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA.

Johnston SC, Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y; THALES Investigators. N Engl J Med. 2020 Jul 16;383(3):207-217. doi: 10.1056/NEJMoa1916870. PMID: 32668111