66 Matching Annotations
  1. Jan 2022
    1. Home

      Zuo, F., Abolhassani, H., Du, L., Piralla, A., Bertoglio, F., Campos-Mata, L. de, Wan, H., Schubert, M., Wang, Y., Sun, R., Cassaniti, I., Vlachiotis, S., Kumagai-Braesch, M., Andréll, J., Zhang, Z., Xue, Y., Wenzel, E. V., Calzolai, L., Varani, L., … Pan-Hammarström, Q. (2022). Heterologous immunization with inactivated vaccine followed by mRNA booster elicits strong humoral and cellular immune responses against the SARS-CoV-2 Omicron variant (p. 2022.01.04.22268755). https://doi.org/10.1101/2022.01.04.22268755

  2. Dec 2021
    1. ReconfigBehSci. (2021, November 26). maybe this is a good moment to remind people that makers of mRNA vaccines have been extensively prepping for the possibility of new variants. Biontech/Pfizer have given a timeline of 100 days to the delivery of a retooled version of their vaccine [Tweet]. @SciBeh. https://twitter.com/SciBeh/status/1464225264523747359

    1. Garcia-Beltran, W. F., Denis, K. J. S., Hoelzemer, A., Lam, E. C., Nitido, A. D., Sheehan, M. L., Berrios, C., Ofoman, O., Chang, C. C., Hauser, B. M., Feldman, J., Gregory, D. J., Poznansky, M. C., Schmidt, A. G., Iafrate, A. J., Naranbhai, V., & Balazs, A. B. (2021). MRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant (p. 2021.12.14.21267755). https://doi.org/10.1101/2021.12.14.21267755

    1. Bert Hubert’s excellent and widely shared article about Reverse Engineering the source code of the Pfizer-BioNTech SARS-CoV-2 Vaccine

      These 2 articles form an informational island on covid19 mRNA vaccines.

    1. Translational kinetics of mRNA-LNP delivered by different routes in vivo. Quantification of the bioluminescent signal measured in BALB/c mice injected with (A) 0.1 μg, (B) 1.0 μg or (C) 5.0 μg mRNA-LNPs by intradermal (i.d.), intramuscu

      Diagrams of the presence of proteins versus time in various administration methods in mouse

    1. In this mouse model, the mRNA hit the hepatocytes and caused them to make plenty of luciferase, but not for long: at Day 1, the livers were lit up like a used car lot, but by Day 3, everything was gone. At that point, though, there was still some light coming from the sites of injection.

      Where does all the mRNA end up, according to this 2015 study on mice](https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4624045/)?

      Here we learn stuff not reorted in the paper.

  3. Nov 2021
    1. It remains unclear whether the reduction in the neutralization sensitivity of the N501Y.V2 strain to vaccine-induced antibodies is enough to seriously reduce vaccine efficacy. First, mRNA vaccines also induce virus-specific helper T cells and cytotoxic T cells, both of which might be involved in protection against challenge. Also, the mRNA vaccines, in particular, induce such a strong NAb response that there could be enough “spare capacity” to deal with reductions in the sensitivity of the variant to NAbs. In other words, N501Y.V2 (and the related virus from Brazil) may be less sensitive to NAbs, but not to an extent that will cause widespread vaccine failure.

      Variants that show reduced sensitivity to NAbs don't necessarily mean mRNA vaccine failure

      New variants may emerge that show reduced sensitivity to NAbs.

      This may not result in vaccine failure because:

      1. The mRNA vaccines induce such a strong NAb response, there will be enough spare capacity to deal with the virus.
      2. The mRNA vaccines also induce other virus specific protection such as helper T cells and cytotoxic T cells, which may not be affected by the reduction in NAb sensitivity.
    1. Monto, A. S. (2021). The Future of SARS-CoV-2 Vaccination—Lessons from Influenza. New England Journal of Medicine, 0(0), null. https://doi.org/10.1056/NEJMp2113403

    2. The effect on asymptomatic infections was a welcome surprise, because it has been thought that most vaccines for respiratory illnesses, including influenza, are “leaky” — that is, they allow some degree of asymptomatic infection and are better at preventing symptomatic infection.

      Most vaccines for respiratory illnesses are leaky.

      The efficacy the mRNA vaccines showed in preventing asymptomatic transmission was therefore a welcome surprise.

  4. Oct 2021
    1. Tartof, S. Y., Slezak, J. M., Fischer, H., Hong, V., Ackerson, B. K., Ranasinghe, O. N., Frankland, T. B., Ogun, O. A., Zamparo, J. M., Gray, S., Valluri, S. R., Pan, K., Angulo, F. J., Jodar, L., & McLaughlin, J. M. (2021). Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: A retrospective cohort study. The Lancet, 398(10309), 1407–1416. https://doi.org/10.1016/S0140-6736(21)02183-8

    1. Following IM administration, the maximum concentration (Cmax) of the injection site muscle was 5,680 ng/mL, and the level declined with an estimated t1/2 of 18.8 hr

      Vaccine's halg-life was measured just below a day for mice muscles.

    2. The spleen and liver had a mean Cmax of 86.9 ng/mL

      Spleen & liver had x30 less mRNA concentration than Lymph nodes closest to the vaccine site, and x70 less the injected muscle.

    3. Proximal lymph nodes had the second highest concentration at 2,120 ng/mL (tmax of 8 hr with a relatively long t1/2 of 25.4 hr)

      Lymph-node mRNA half-life is a day.

    1. Lucas, C., Vogels, C. B. F., Yildirim, I., Rothman, J. E., Lu, P., Monteiro, V., Gelhausen, J. R., Campbell, M., Silva, J., Tabachikova, A., Peña-Hernandez, M. A., Muenker, M. C., Breban, M. I., Fauver, J. R., Mohanty, S., Huang, J., Shaw, A. C., Ko, A. I., Omer, S. B., … Iwasaki, A. (2021). Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature, 1–9. https://doi.org/10.1038/s41586-021-04085-y

    1. Barros-Martins, J., Hammerschmidt, S. I., Cossmann, A., Odak, I., Stankov, M. V., Morillas Ramos, G., Dopfer-Jablonka, A., Heidemann, A., Ritter, C., Friedrichsen, M., Schultze-Florey, C., Ravens, I., Willenzon, S., Bubke, A., Ristenpart, J., Janssen, A., Ssebyatika, G., Bernhardt, G., Münch, J., … Behrens, G. M. N. (2021). Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination. Nature Medicine, 1–5. https://doi.org/10.1038/s41591-021-01449-9

  5. Sep 2021
    1. Published clinical data on the safety of mRNA-LNP vaccines are scarce, in comparison with siRNA, and are limited to local administration (ID and IM).

      Safety of mRNA vaccines.

    2. Although LNPs are promising delivery systems, safety issues need to be addressed to enable proper clinical development of LNP-formulated mRNA vaccines. LNPs’ potential toxicity could be complex and might manifest in systemic effects due to innate immune activation (induction of pro-inflammatory cytokine production), and/or in local, cellular toxicity due to accumulation of lipids in tissues (Hassett et al. 2019; Semple et al. 2010; Sabnis et al. 2018). Toxicity could potentially be abrogated, or reduced, by the administration of prophylactic anti-inflammatory steroids or other molecules and/or using biodegradable lipids (Hassett et al. 2019; Abrams et al. 2010; Tabernero et al. 2013; Tao et al. 2011). LNPs can also activate the complement system and might potentially elicit a hypersensitivity reaction known as complement activation-related pseudoallergy (CARPA) (Dezsi et al. 2014; Mohamed et al. 2019; Szebeni 2005, 2014), which can be alleviated using different strategies such as steroid and anti-allergic premedication (i.e., dexamethasone, acetaminophen, and antihistaminic drugs) or the use of low infusion rates during intravenous administration (Mohamed et al. 2019; Szebeni et al. 2018). Alternatively, co-delivery of regulatory cytokines (i.e., IL-10) using LNPs might be a viable strategy to reduce potential LNP-associated adverse events.

      Safety of mRNA Liquid Nanoparticles

  6. Aug 2021
    1. Hillus, David, Tatjana Schwarz, Pinkus Tober-Lau, Hana Hastor, Charlotte Thibeault, Stefanie Kasper, Elisa T. Helbig, et al. “Safety, Reactogenicity, and Immunogenicity of Homologous and Heterologous Prime-Boost Immunisation with ChAdOx1-NCoV19 and BNT162b2: A Prospective Cohort Study,” June 2, 2021. https://doi.org/10.1101/2021.05.19.21257334.

    1. Tenbusch, M., Schumacher, S., Vogel, E., Priller, A., Held, J., Steininger, P., Beileke, S., Irrgang, P., Brockhoff, R., Salmanton-García, J., Tinnefeld, K., Mijocevic, H., Schober, K., Bogdan, C., Yazici, S., Knolle, P., Cornely, O. A., Überla, K., Protzer, U., … Wytopil, M. (2021). Heterologous prime–boost vaccination with ChAdOx1 nCoV-19 and BNT162b2. The Lancet Infectious Diseases, 0(0). https://doi.org/10.1016/S1473-3099(21)00420-5

  7. Jul 2021
    1. Collier, D. A., Ferreira, I. A. T. M., Kotagiri, P., Datir, R., Lim, E., Touizer, E., Meng, B., Abdullahi, A., Elmer, A., Kingston, N., Graves, B., Gresley, E. L., Caputo, D., Bergamaschi, L., Smith, K. G. C., Bradley, J. R., Ceron-Gutierrez, L., Cortes-Acevedo, P., Barcenas-Morales, G., … Gupta, R. K. (2021). Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2. Nature, 1–9. https://doi.org/10.1038/s41586-021-03739-1

  8. Jun 2021
  9. May 2021
    1. Eric Topol. (2021, May 1). Downgrading the concern on B.1.617, the poorly named ‘double mutant’—98% effectiveness of mRNA vaccine in an Israeli outbreak @CT_Bergstrom https://t.co/tGbuwPUmAL —Lab studies: Minimal immune evasion, expected full protection from vaccine @GuptaR_lab https://t.co/AIp24G0ROK https://t.co/AK20UWlDBD [Tweet]. @EricTopol. https://twitter.com/EricTopol/status/1388539223230140422

    1. Dr. Tom Frieden. (2021, April 30). Globally, the end of the pandemic isn’t near. More than a million lives depend on improving our response quickly. Don’t be blinded by the light at the end of the tunnel. There isn’t enough vaccine and the virus is gathering strength & speed. Global cooperation is crucial. 1/ [Tweet]. @DrTomFrieden. https://twitter.com/DrTomFrieden/status/1388172436999376899

  10. Apr 2021
    1. Kustin, T., Harel, N., Finkel, U., Perchik, S., Harari, S., Tahor, M., Caspi, I., Levy, R., Leschinsky, M., Dror, S. K., Bergerzon, G., Gadban, H., Gadban, F., Eliassian, E., Shimron, O., Saleh, L., Ben-Zvi, H., Amichay, D., Ben-Dor, A., … Stern, A. (2021). Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals. MedRxiv, 2021.04.06.21254882. https://doi.org/10.1101/2021.04.06.21254882

  11. Feb 2021
    1. Andrew💙Croxford. (2020, December 3). NEW THREAD: possible development of anti-Syncytin responses after immunization with the SARS-CoV-2 spike protein-coding mRNA vaccines, based on a ‘homologous’ region shared between these proteins. [Tweet]. @andrew_croxford. https://twitter.com/andrew_croxford/status/1334593606196187136

  12. Jan 2021
    1. mRNA vaccines are a new type of vaccine to protect against infectious diseases. To trigger an immune response, many vaccines put a weakened or inactivated germ into our bodies. Not mRNA vaccines. Instead, they teach our cells how to make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies. That immune response, which produces antibodies, is what protects us from getting infected if the real virus enters our bodies.
    1. the mRNA in the vaccine contains instructions to tell our body how to build a coronavirus spike protein. As soon as we do that, our immune system freaks out, as it’s supposed to, and creates antibodies to the spike protein. The mRNA is destroyed shortly after the injection, but the antibodies stick around. They can then recognize the real virus if we ever encounter it in the wild.
  13. Nov 2020
    1. transcriptionalleve

      This is the process of a complementary mRNA copy of a single gene on the DNA that is created in the nucleus. The mRNA is smaller than the DNA so it can carry the genetic code into the ribosome and into the cytoplasm that enables the protein creation.

    1. intracellular signaling

      This is an important mechanism that cells can respond to their environment and extracellular cues. Cells sense their environment and modify genes, mRNA splicing, protein expression and protein modifying to respond to these cues.

  14. Oct 2020
    1. messenger RNA (mRNA)

      This is a single strand on an RNA molecule that leaves the the nucleus of a cell in order to relocate to the cytoplasm. This is where the mRNA can help create the protein for the cell in a process known as protein synthesis. The mRNA takes in information passed into it by DNA and decode it for the ribosomes to make more protein for the cell to live on.

  15. Aug 2020
    1. Corbett, K. S., Edwards, D. K., Leist, S. R., Abiona, O. M., Boyoglu-Barnum, S., Gillespie, R. A., Himansu, S., Schäfer, A., Ziwawo, C. T., DiPiazza, A. T., Dinnon, K. H., Elbashir, S. M., Shaw, C. A., Woods, A., Fritch, E. J., Martinez, D. R., Bock, K. W., Minai, M., Nagata, B. M., … Graham, B. S. (2020). SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature, 1–8. https://doi.org/10.1038/s41586-020-2622-0

  16. Jul 2020