1/Been a lot of recent talk about virus mutations/transients that might result. Some think natural infections likely to bring about dangerous strains, others fear the vaccines deployed in the midst of a pandemic are more of a concern.
nature.com/articles/s4156…
nature.com/articles/s4156…
2/ “...mutations are a natural part of the virus life cycle and rarely impact outbreaks dramatically.”
3/“...individual mutations seldom become fixed during outbreaks nor modulate complex virological traits. Rather, mutation is a humdrum aspect of life for an RNA virus. “
4/“.....although a mutation that changes how a virus is transmitted or its virulence may readily appear in a virus population, it will not spread to high frequencies unless it is selectively advantageous
5/At the same time, epidemiologically relevant traits like the viral mode of transmission and virulence can be controlled by multiple genes. As such, they are likely beholden to stringent evolutionary constraints because they require multiple mutations to evolve. “
6/Indeed, across a broad swathe of viruses it is unusual to find those that have changed or expanded their mode of transmission over short evolutionary time-scales despite high rates of mutation
7/“Mutations can also make a virus either more or less virulent. A common idea is that virulence will only change — either upwards or downwards — if it increases the transmission rate of the virus, which effectively means an increase in the number of virus ‘offspring’. “
7a/However, high virulence may (although by no means always) reduce transmissibility if the host is too sick to expose others.
8/“Without information on the precise evolutionary forces and selection pressures in operation, predicting how virulence might evolve is an extremely difficult and perhaps futile task.”
9/“Mutations are requisite during host jumps, for example, when a virus ‘spills over’ from an animal reservoir into humans or utilizes an alternate arthropod vector for transmission.”
10/“It is also hypothesized that mutations in highly pathogenic avian influenza A(H5N1) could lead toward more efficient human-to-human transmission, although thankfully this has yet to occur.
11/...we can look to the 2002–2003 SARS-CoV epidemic. Large deletions in the open reading frame 8 region and mutations in the spike protein were discovered during the early stages of the outbreak and eventually dominated the epidemic, suggesting these were adaptations to humans.
12/Based on this observation, some hypothesized that virus genetic changes in part drove the SARS epidemic, but this claim is unsubstantiated.
13/ So, could SARS-CoV-2 adapt in the same way? Yes. Will adaptation precipitate more deaths? Unlikely...
Mutations are not indicative of outlandish and devastating new viral characteristics. Mutation is an inevitable consequence of being a virus.”
Mutations are not indicative of outlandish and devastating new viral characteristics. Mutation is an inevitable consequence of being a virus.”
14a/Marek’s disease — a highly contagious, paralyzing and ultimately deadly ailment that costs the chicken industry more than $2 billion a year — might be evolving in response to its vaccine.
15/Today, the poultry industry is on its third vaccine. It still works, but Read and others are concerned it might one day fail, too — and no fourth-line vaccine is waiting. Worse, in recent decades, the virus has become more deadly.
16/U.S. Department of Agriculture, posit that the virus that causes Marek’s has been changing over time in ways that helped it evade its previous vaccines.
17/In a 2015 paper in PLOS Biology, Read and his colleagues vaccinated 100 chickens, leaving 100 others unvaccinated. They then infected all the birds with strains of Marek’s that varied in how virulent — as in how dangerous and infectious — they were.
18/The team found that, over the course of their lives, the unvaccinated birds shed far more of the least virulent strains into the environment, whereas the vaccinated birds shed far more of the most virulent strains
19/The findings suggest that the Marek’s vaccine encourages more dangerous viruses to proliferate. This increased virulence might then give the viruses the means to overcome birds’ vaccine-primed immune responses and sicken vaccinated flocks.
20/Immunization is also making once-rare or nonexistent genetic variants of pathogens more prevalent, presumably because vaccine-primed antibodies can’t as easily recognize and attack shape-shifters that look different from vaccine strains.
21/Evolutionary biologists aren’t surprised ... A vaccine is a novel selection pressure placed on a pathogen, and if the vaccine does not eradicate its target completely, then the remaining pathogens with the greatest fitness — those able to survive, .. will become more common. “
22/Yet don’t mistake these findings as evidence that vaccines are dangerous or that they are bound to fail — because undesirable outcomes can be thwarted by using our knowledge of natural selection, too. Evolution might be inevitable, but it can be coaxed in the right direction.
23/many vaccines don’t provide lifelong immunity, for a variety of reasons. A new flu vaccine is developed every year because influenza viruses naturally mutate quickly.
23a/Vaccine-induced immunity can also wane over time. Research suggests a drop in protection over time occurs with the mumps vaccine, too.
24/Vaccine failures caused by vaccine-induced evolution are different. These drops in vaccine effectiveness are incited by changes in pathogen populations that the vaccines themselves directly cause.
25/. When an RNA virus replicates, the copying process generates one new error, or mutation, per 10,000 nucleotides, a mutation rate as much as 100,000 times greater than that found in human DNA
26/. In 1992, recommendations from the U.S. Centers for Disease Control and Prevention (CDC) began promoting a new vaccine to prevent the infection, which is caused by bacteria called Bordetella pertussis.
27/The old vaccine was made using whole killed bacteria, which incited an effective immune response but also caused rare side effects, such as seizures.The new version, known as the “acellular” vaccine,contained just two to five outer membrane proteins isolated from the pathogen.
28/The unwanted side effects disappeared but were replaced by new, unexpected problems. First, for unclear reasons, protection conferred by the acellular vaccine waned over time. Epidemics began to erupt around the world.
29/vaccination was inciting evolution, causing strains of the bacteria that lacked the targeted proteins, or had different versions of them, to survive preferentially.
30/In Australia, B. pertussis samples from 320 patients between 2008 and 2012 were sequenced. The percentage of bacteria that did not express pertactin, a protein targeted by the acellular vaccine, leapt from 5 percent in 2008 to 78 percent in 2012.
31/ In the U.S., nearly all circulating viruses lack pertactin, according to a 2017 CDC paper. “I think pretty much everyone agrees pertussis strain variation is shaped by vaccination,”
32/The current Hepatitis B vaccine, targets a portion of the virus known as the hepatitis B surface antigen. It was introduced in the U.S. in 1989.
32a/A year later, in a paper published in the Lancet, researchers detected circulating hepatitis B viruses in 44 vaccinated subjects, but in some of them, the virus was missing part of that targeted antigen.
33/ In Taiwan researchers sequenced the viruses that infected children who had tested positive for hepatitis B. They reported that the prevalence of these viral “escape mutants”, that lacked the surface antigen had increased from 7.8 percent in 1984 to 23.1 percent in 1999.
34/ in 2000 A new vaccine called Prevnar 7 was developed to prevent infections caused by Streptococcus pneumoniae. Scientists had discovered more than 90 distinct S. pneumoniae serotypes and Prevnar 7 targeted the seven most common serotypes
35/while Prevnar 7 almost completely eliminated infections with the seven targeted serotypes, the other, rarer serotypes quickly swept in to take their place, including a serotype called 19A
36/ in 2010, the U.S. introduced a new vaccine, Prevnar 13, which targets 19A and five additional serotypes. Previously unseen serotypes have again flourished in response. A 2017 paper in Pediatrics compared the situation to a high-stakes game of whack-a-mole.
37/Overall, the incidence of invasive pneumococcal infections in the U.S. has dropped dramatically among children and adults as a result of Prevnar 13. It is saving many American lives, presumably because it targets the subset of serotypes most likely to cause infections.
38/ In England while infections in kids have dropped, pneumococcal infections have been increasing in older adults and are much higher now than they were before Prevnar 7 was introduced. The serotypes that are now carried by children are better able to cause disease in adults.
39/ One can think about vaccination as a kind of sieve, argues Troy Day, a mathematical evolutionary biologist .
39a/Leaky vaccines prevent many pathogens from passing through and surviving, but if a few squeeze by, those in that nonrandom sample will preferentially survive, replicate and ultimately shift the composition of the pathogen population.
40/The ones that leak through might be escape mutants with genetic differences that allow them to hide from vaccine-primed antibodies, or they may simply be serotypes that weren’t targeted by the vaccine in the first place.
41/ Most of the vaccines we get in childhood prevent pathogens from replicating inside us and thereby also prevent us from transmitting the infections to others. These are called sterilizing vaccines
42/ researchers have been developing immunizations that prevent disease without actually preventing infections — what are called “leaky” vaccines. And these new vaccines may incite a different, and potentially scarier, kind of microbial evolution.
42/Virulence, as a trait, is directly related to replication: The more pathogens that a person’s body houses, the sicker that person generally becomes.
42a/A high replication rate has evolutionary advantages — more microbes in the body lead to more microbes in snot, which gives the microbes more chances to infect others — but it also has costs, as it can kill hosts before they have the chance to pass on their infection.
43/The problem with leaky vaccines, Read says, is that they enable pathogens to replicate unchecked while also protecting hosts from illness and death, thereby removing the costs associated with increased virulence.
44/Over time, then, in a world of leaky vaccinations, a pathogen might evolve to become deadlier to unvaccinated hosts because it can reap the benefits of virulence without the costs This virulence can also cause the vaccine to start failing by causing illness in vaccinated hosts
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