Kiki’s Comments                                                                                                        May 2020

                                    TWiV 613: Jenner, Vaccines, and COVID-19

            Key Points:

*be discerning with the information being disseminated—look at the sources, biases, and transparency being reported

*there is an interesting vectored mRNA vaccine being investigated at Oxford University’s Jenner Institute

*Remdesivir has been showing beneficial therapeutic use early in the course of the infection in humans

*unlikely that there are different mutations that have largely changed the pathogenicity within the CoV-2 infections

*we do not know if immunity is sterilizing or not for CoV-2 and people who have recovered can still act as walking fomite vectors; be aware that there are other diseases (e.g. seasonal flu) that may have similar symptoms to those described from COVID-19, so without a test it is difficult to determine CoV-2 infection or recovery

            General Discussion:

*Mother Jones Science Has an Ugly Dark Side Article: three criteria for how you should evaluate a news article: 1) transparency in contribution (have to be able to track the references), 2) participation in the scientific ecosystem (legitimacy of publication), 3) transparency of motivation. Real science takes time and is self-correcting. Be aware that not all, maybe not even most, publications meet all of these standards. Be discerning and find reliable sources.

*History of Edward Jenner: father of immunizations and vaccines. He took puss from the lesion of a woman’s hand who had cow pox and put it into a boy. He then challenged the child with smallpox and the boy did not get sick. This was the first experiment that showed vaccination (the name coming from the latin word for cow) was possible. This was the beginning of vaccinology, virology, and part of epidemiology. 

*Moderna’s mRNA Vaccine & Oxford’s Jenner Institute Vectored Vaccine: this is an adenovirus vectored vaccine. Adenovirus is one of the common cold viruses that is a DNA virus in which you can more easily insert the genes of other viruses—here we are inserting the SARS-CoV-2 spike protein. In 2001, recombineering (recombination-mediated genetic engineering) was first used, in which you put the entire adenovirus genome in a bacterial plasmid to be propagated in bacteria; important because it is difficult to work on large genomes and this mechanism uses positive and negative selection to generate the vector. For the CoV-2 vaccine, they are using a chimpanzee adenovirus so that there will be no preexisting immunity in the human community. This chimp adenovirus is missing the E1 gene, which is essential for replication, and has an inserted human E4 gene. When this new virus infects human cells, there will be gene expression of the transgene and the E4 genes (some chimp and some human adenovirus) that will cause protein, but not new adenovirus, to be made.

n.b.i. viral vector vaccine technology is relatively novel, as there are two licensed viral-vectored vaccines

n.b.ii. fast-tracking is a relative term when it comes to vaccines—many of the trials are scheduled to terminate in 2021

*Remdesivir: the Remdesivir large trial was stopped recently because it showed mild positive effect, so was given to the placebo group as well. Earlier administration is better. 


*Mercia: can you discuss the theory of different strains of CoV-2 causing the different symptoms? It is very unlikely that there are different mutations that have largely changed the pathogenicity within the CoV-2 infections. Remember that studies in non-human animals are not directly equatable to humans and disease dynamics.

*Amy: could effective therapeutics have as much of an effect on the pandemic as a vaccine? The problem of the therapeutics is who you give them to—if you wait to give them to people very sick in the hospital, it is likely too late or will have minimal benefit. The timing of antivirals is crucial and unless we have an instant and reliable test for infection, it is likely too late to administer a therapeutic. Also, some therapeutics cannot be taken at home (eg Remdesivir is given through an IV), which will make administration more difficult. That said, therapeutics will play an important role and we should still try things. A vaccine could be more universally administered and will be more useful.

*Lewis: are medical staff at higher risk of infection than non-medical workers? There is no evidence that there are higher infection rates for medical professionals.

*Anonymous: if my housemate is “immune” due to a previous infection, but comes into contact with someone who is infected, can she begin shedding virus again? No, this is unlikely. On the other hand, if she came in contact with an infected individual, she can serve as a vector or walking fomite. If she is in fact immune, and this is a big if as we do not know much about immunity in this case, then she should not replicate virus to any high titer. Again, we do not know if immunity is sterilizing or not for CoV-2, so she could still be spreading the virus. Also, if people believe they have been infected, but are not positive, they may have had a different illness and may still be able to get infected and spread the infection. 

*David: can you speak a bit about diagnostic testing? The take home message is that sensitivity and selectivity of tests are raw values, but the meaning can change depending on the disease. When you have high or low prevalence it impacts how you put people together and isolate people, the accuracy of testing can be even more important. MPV and PPV are important. Diagnostics are very important for determining pervasiveness of the infection and responses to it. Not all tests are reliable and there have been varying false positive and false negatives that need to be taken into account.

*Ted: Is there a way to protect people as we reopen from spreading the virus? Everyone going back into society will have to accept and understand the risks. It will take a while and some of our at risk people may have to isolate and stay home for longer. Use personal protective equipment, try to maintain social distancing and increased hygienic behaviors, and do not put yourself into undue risk.

*Amelia: can you discuss the COVID-19 and viral disease sniffing dogs? Patients have a particular scent, at least in the case of Parkinson’s Disease, so it is possible that patients with COVID-19 would emit different vapors to other people. It would be very interesting if the organic molecular changes causes different organic vapors to be released by both symptomatic and asymptomatic people for COVID-19, as this would be helpful. The idea is not crazy, but it may be hard to train a dog to identify these. 

*Asal: what is the relationship of CT-value to PCR-positive viral load? RNA is not enough to calculate viral load—this is why its called viral load and not RNA load. A CT-value is a cycle-threshold for how many cycles you need to go through before you can detect your product from your template. This has to be calibrated very carefully to the virus.

*Manoy: do you think that people in India are less susceptible to CoV-2 because of the vaccinations given in the country? We do not know how much testing is being done, so don’t draw any conclusions about population susceptibility. We need a trial to be done that controls for all factors and varies the vaccination before we could conclude anything.