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 ...


28

Vaccine efficacy Pfizer's target measures for efficacy (see the study on clinicaltrials.gov) seem to be: Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination From Pfizer's study plan (VE = vaccine efficacy): VE ...


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 ...


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-...


12

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. ...


11

It means protection against the virus brought to you by the vaccination. Around 45.000 people participate in the trial; 50% of these are vaccinated with the trial vaccine and 50% receive a placebo. Additionally, you exclude people from the trial who had had COVID-19 before. Because infecting people with a potentially deadly disease is not possible ethically, ...


10

Expectations for accelerated vaccine development are based on two main points. Groups have been working on vaccines for SARS-CoV-1 since 2003, and much of that work is applicable to SARS-CoV-2 (the COVID-19 virus). Here is a review article discussing work on SARS-2 vaccines based on work on SARS and MERS. One example, transgenic mice are available that ...


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 ...


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

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

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 ...


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 ...


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

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 ...


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

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 ...


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 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

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 ...


5

It's a weekly cycle due to reporting disruptions over the weekend. Use a 7-day moving average to get a better picture. Holidays and such can still be disruptive but the 7-day average solves most of it.


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

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 ...


4

This is the temperature at which RNA is stored for long term storage without the occurance of degradation. It is also standard lab routine to store RNA at this temperature. Conviniently, this temperature can be reached by dry ice (-78°C), which makes shipping a lot easier. However, there are indications by Biontech themselves that the vaccine will be stable ...


4

We cannot say if the virus in ferrets gets less or more dangerous than the one which actually circulates in humans. There are two problems with this infection: The ferrets can build a reservoir for the virus making it possible for circulation to occur among these animals and re-introduce it into the human population. It may also be possible that the virus ...


4

Even though the DNA sequence may be 90+% similar between two species, individual amino acids can make a huge difference in the interaction between two proteins. In this case, the most relevant proteins are the coronavirus spike protein and the ACE2 enzyme expressed on the surface of target cells. Even in the limited amount of time SARS-CoV-2 has existed and ...


4

The issue is using the number of positive tests as a measure for the total number of active cases at a given time. At least in the U.K., the early testing capacity was much lower than it was now: Because of this, many people who were infected were not being tested and so weren't included in the total number of infections. Therefore, the total number of ...


4

Data are usually binned in broad age groups partly because that's all the detail that's useful in some context, and because access to more detailed data often involves access to strongly controlled, personally identifiable information. This preprint (full disclosure: I'm a co-author) gives information in 2-year bins for COVID in Ontario, e.g. this graph of ...


4

I tried to break down your question into smaller parts and answer them individually: Q. What is immunity? A. Simply put, immunity is the ability to react to an infectious agent and stop it from causing disease. Q. Do vaccines make you immune to infectious diseases? A. Yes, by definition. If it doesn't make you immune, it's not a vaccine. Q. Can we get ...


4

It is not a coincidence, but it doesn't have to do with sudden evolutionary changes, rather with human behavior. The three viruses you mention are zoonotic — they can infect different species, including humans. Increased development of formerly untouched lands is bringing people into contact with animals (and existing, but formerly unknown zoonotic pathogens)...


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