37

Answering my own question after reading the 2018 Nature review article “mRNA vaccines — a new era in vaccinology” The resources and motivation engendered by the COVID-19 pandemic are a major factor in the development of the first mRNA vaccines approved by national governments. However, before the COVID-19 pandemic, there were recent advances in mRNA vaccine ...


29

Yes, this is the effect of the vaccine. A reduction of infections of over 88%, a reduction of severe cases and death by 95% and higher. See reference 1 for the details. Data from the ReCoVAM Study from Malaysia (unfortunately only not yet published, so see here) shows a reduction of infection by 88% and a reduction of admission to ICU/death by up to 96%. So ...


27

This is not completely clear to say the least, but there are some hints. Please keep in mind that there was not much time for extensive research, since this disease is still quite new. What seems clear (at least at the moment) is that most like the nerve cells (in the olfactory bulb as well as in the taste bud) are not directly affected, since they do not ...


22

Since vaccination is not 100% protective against infection (i.e. the virus can sometimes succeed in establishing and replicating in a vaccinated host's body), the answer is yes. Furthermore, since vaccination is also not 100% protective against transmission — although it does lower the probability of transmission from infected individuals — such mutations ...


13

To enhance stability and translation efficiency according to {1}: The 5′UTR (TEV) [8,21] and 3′ UTR (F-I) of this construct have been shown to enhance stability and translation efficiency, as has the 100-nucleotide poly(A) tail interrupted by a short linker (A30LA70, where L = GCAUAUGACU) [22] References: {1} Stadler, C., Bähr-Mahmud, H., Celik, L. et al. ...


13

Very simply, mutations do occur, as they do for any cultured organism. This is a well recognized problem in many fields of biology where organisms are cultured and remains in particular a problem for cultured mammalian cell research. As far as I know there is no method for slowing or altering the rate of mutation as this is an inherent part of the RNA-...


11

These Chimpanzee adenoviral vectors do not bypass the innate immune system at all. In fact they are used precisely because of their activation of the innate immune system, which then results in greater immunity because activation of the innate immune system results in antigen presentation and then activation of the adaptive immune system. The reason they ...


10

Simple answer: This vaccine trial compared their trial vaccine against saline. See the original publication by Biontech and Pfizer in the New England Journal of Medicine linked below. The relevant information can be found in the methods section: TRIAL PROCEDURES With the use of an interactive Web-based system, participants in the trial were randomly ...


10

While the linked paper presents interesting results, the conclusions must be interpreted in context of their in vitro methods and cannot be readily extrapolated to understand the in vivo effect of SARS-CoV-2 mRNA-LNP vaccines. Here is their important caveat: Although no evidence has been published that SARS–CoV–2 can infect thymocytes or bone marrow ...


9

No, this is not possible, as the vectors used for the vaccination cannot replicate anymore. Some of the genes necessary for this step have been removed from the viral genome to prevent the uncontrolled spread and replaced by the spike protein which is used as the antigen for the vaccination. To replicate the virus in the production process, a special cell ...


9

The authors explicitly suggest the first part of your question in their discussion section: indicating that full–length spike–based vaccines may inhibit the recombination of V(D)J in B cells, However, for this to have a meaningful effect on the immune system as a whole requires that a significant portion of B cells uptake the vaccine and express spike ...


8

While I get your intuition, the hypothesis seems implausible Emerge of new CoV variants should be considered proportional to the current spread of the virus. Each virus has a certain mutation rate that surely does not depend on lock-downs. It seems implausible to interpret lock-downs as physical limitations to viral spread, that could potentially be ...


8

To judge about this assay, it is important to see how they worked. They used different sets of primers to analyze for SARS-CoV-2. Namely targets IP2 und IP4 from Institute Pasteur in Paris (see reference 1) and to validate results also primers targeting the "E" sequence (reference 2) and two against the nucleoproteins N1 and N2 (reference 3). Then ...


8

For Covaxin (BBV152), SARS-CoV-2 was inactivated by treatment with β-propiolactone [1]. β-propiolactone reacts with and modifies, among other things, nucleic acids, thus preventing their replication [2]. [1] Yadav P, Ella R, Kumar S, et al. 2020. Remarkable immunogenicity and protective efficacy of BBV152, an inactivated SARS-CoV-2 vaccine in rhesus macaques....


8

Well, we can work this out empirically. We know that the average molecular mass of a base of a RNA is 339.5 g/mol. However to calculate the approximate molecular mass of a single-stranded RNA molecule, you multiply the number of bases by 320.5 and add 159 (same source). This means for a single-stranded molecule of 1000 bases, it will have a molecular mass of ...


8

This is a lateral flow assay. [image source] A sample is applied at one end of the strip and flows across to the other side by capillary action. It first encounters antibodies against the target antigen and which are conjugated to some reporter (in the image above, the reporter is colloidal gold). When the sample contacts these antibodies, they too will ...


7

Saying that a vaccine is $95\%$ efficacious is neither claiming that it works $95\%$ of the time nor that it protects $95\%$ of its recipients.† Rather, a $95\%$ efficacy means that—during the clinical trial in which half the subjects had been vaccinated and half hadn't—among those who eventually developed the disease, the ratio of those who had been ...


7

The spike proteins expressed by cells that take up mRNA or ChAdOx vaccines are modified so they cannot induce membrane fusion. However, the research article you refer to indicates that circulating spike protein damages endothelial cells simply by binding ACE2, which suggests vaccine derived spike protein could still cause this kind of damage if it enters the ...


7

Both the AstraZeneca (AZ) and Janssen (J) vaccines against SARS-CoV-2 work by using what is known as a viral vector to generate an immune response. In both cases these vaccines use an Adenovirus as the vector (vector in this case means "carrier"). Adenoviruses are a family of double-stranded DNA viruses, most commonly known for being one of the ...


7

The CDC has evaluated COVID-19 vaccines for pregnant people, and has determined that they are safe. The main worry that they were addressing, however, was not either of your concerns (which do not make sense biologically). Instead, they were looking at whether the reaction of the body to the vaccine would be a potential cause of miscarriage. The answer is: ...


6

The two stop codons are obviously to prevent read-through of the termination codon. Why this should be necessary is not clear to me, but the following may be relevant: The synthetic mRNA differs from the natural mRNA in a particular respect that is easier to explain with reference to the transcript map of the virus, below. The two ORFs 1a and 1b are ...


6

This is more plausible (second point below) and less plausible (third point below). Selective advantage The emergence of a new strain of a virus relates to the selective advantage (Gordo 2009). This selective advantage might be that the reproduction rate is relatively higher. Reproduction rate The selective advantage (in terms of relative growth rate) is ...


6

The mRNA won't be entirely perfect, but the imperfections will not matter. The spike protein is big, encoded by thousands of base pairs in the virus. In the virus itself, it's not entirely homogeneous: there are always going to be small mutations that cause different variants to be produced, but nearly all of those are nearly identical. The mRNA in a vaccine ...


6

In short, no. It's not harmful but it won't do anything to prevent or mitigate the current infection. How vaccines work in general is that they train the immune system to respond to an infection so that they are prepared for it. Generally protein component of the virus or an inactivated form of the pathogen is used as a vaccine. The immune system recognises ...


6

The innate immune system has many different components to it. If we consider a natural virus, like the base adenovirus used as a vector used in the Oxford/AstraZeneca vaccine, then we can assume that the virus already has sufficiently effective strategies in place to deal with them. In particular: Physical and chemical barriers are irrelevant, given an ...


5

This is simply a coincidence. A RNA Virus will mutate all the time (although this one is pretty stable), there are thousands of known mutations (see Nextstrain for detailed information). It is only a matter of time, until one of these will dominate the others. It may also be the effect of a few superspreading events where one virus type is strongly promoted,...


5

Interesting question! Yes, the hydrophobic amino acids are very important; they facilitate interaction with the hydrophobic (inner) portion of the lipid bilayer. A useful review focusing on the bilayer side that I'll reference throughout this answer is here: Mechanics of membrane fusion, doi: 10.1038/nsmb.1455. (a) shows a model of two lipid bilayers fusing (...


4

The answer is yes, as there is no indication that SARS-COV-2 is an exception to the rule. Cp., for instance: SARS-CoV-2 triggers inflammatory responses and cell death through caspase-8 activation, Shufen Li, Yulan Zhang, Zhenqiong Guan, Huiling Li, Meidi Ye, Xi Ch https://www.nature.com/articles/s41392-020-00334-0 On exceptions to the rule cp., for ...


4

The other answer is a bit convoluted IMHO. First note that as the article cited notes, that's not actually CCA -> CCU but CCA -> CCΨ; they only used ASCII for convenience. Furthermore, these three all code for proline as the article also notes. Second, Ψ stands for pseudouridine and it's the golden discovery of Kariko and colleagues (which made mRNA ...


4

Epidemiological modeling If a virus is able to change so that it renders previous vaccination inefficient, reinfecting those who were previously vaccinated, one could describe this process using epidemiological SIS model (Susceptible-Infected-Susceptible) or its modification that includes a vaccinated group (like SISV model), and indeed estimate how quick ...


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