HOW DIFFICULT WILL IT BE FOR THIS VIRUS TO BE SUBDUED WITH VACCINES?
The currently most hunted quarries in the entire globe are not the reprobates listed on the FBI’s Most Wanted, but a chemical or biological (or both) formulation that can confer a lasting immune response against SARS-CoV-2 in human beings. Worldwide there are as much as 70 research groups working to secure either a vaccine or drug treatment (link).
Again, as in everything COVID-19, the media reports, the politicians, even the experts on the talk shows, are presenting a mish-mash of conflicting and confusing information. I have read about incredulous talk that a vaccine can be achieved in 6 months (link), and a range of other timelines right up to the other end of the extreme where it has been predicted that we may never find a vaccine. (link). The latter is by Boris Johnson, so do NOT believe a word of that statement he issued. The truth is somewhere between these extremes.
To understand all this confusion, it is important to understand the nature of vaccines and their chances of success in relation their interaction with their target – in this case, a virus. This being a blog, I am not going to describe in intricate detail the entire immune response system.
But, very briefly;
Firstly, the immune system evolved to protect against disease and parasites, and to allow the body to heal after injury. To reduce the concept down to cold brass tax biology- everything is food. The immune system prevents its owner from becoming food for microbes for most of its life. Without an immune system, an animal cannot survive. Without an immune system anything and everything can grow and proliferate and thrive in it, and it would quickly die and slowly waste away to bone and dust.
Human infants born with Severe Combined Immunodeficiency (SCID) have little chance in life, and will die quickly unless kept in sterile environments. One example, an American boy managed to live until 12 years old in a sterile “bubble” type environment (link).
So, a microbe enters your bloodstream. Technically speaking it is called an antigen. The type of immune response for a virus is different than for that of bacteria. Bacteria operate outside body cells (very generally speaking) and viruses invade and live inside cells (very generally speaking). A bacterial antigen will be attacked by the immune system via one of a number of pathways: the complement protein mediated lysis pathway; via phagocytosis; via cell mediated immunity. Each one of these pathways have levels of complexity that I cannot go into here. If you wish to know more Google it and have fun. After an immune response to a new antigen, a series of immunological manoeuvres result in the eventual creation of special immune cells called B-cells, or B-lymphocytes. These produce the antibodies that are specific to each antigen (bacteria, virus, anything). Crucially, they may stay active for a very long time in the body and recognise their specific antigen in the future; . The body then has immunity for that disease.
For viruses, the immune response is different. And it is a perfect example of how ingeniously “clever” the immune system appears to be. Since the virus attacks and enters cells, once inside a cell the immune system cannot readily detect the presence of a virus. Sneaky virus! To deal with that, there are a number of immune responses that come into play. Firstly, cells have a system of communication to “show” other cells what is inside them. Utilising protein molecules called “class I major histo-compatibility complex proteins” (or MHC class I), these display examples of proteins that are inside the cell. If there is a viral infection in that cell, then examples of the viral protein will be on display also.
Now, constantly circulating the bodily system is an immune cell called a T-cell, and this cell is part of a surveillance system to detect infections. A certain type of T-cell, called a cytotoxic T-cell, can detect the viral proteins on viral infected cells. Being cytotoxic (meaning it can kill cells) it then destroys this virally infected cell to prevent viral reproduction. In cases where viruses manage to disable the MHC Class 1 activity (thus hide the presence of viral proteins from patrolling T-cells) another type of cell, called natural killer cells, will detect that levels MHC class 1 molecules are less than they should be, and then will kill the cell. Additionally, virally infected cells can produce proteins called interferons, which can disrupt the activity of viral reproduction inside cells. They also act as signalling proteins to neighbouring cells that viral infection is afoot, thereby stimulating the increase of MHC class 1 proteins on other cells, which in turn attracts T-cells to destroy cells in the infected area.
Furthermore, if that particular species/type of virus had been breaking and entering the body previously, there will be those B-cell produced antibodies surveilling the system ready to pounce and destroy viruses before they can actually get access to a cell in the first place. In this case, an animal has immunity to that particular virus. Now, immunity can be time limited; sometimes lasting less than a year, or can be up to 30 years to life such as with measles immunity. That is why many current vaccine programmes require booster shots after a few years, such as TB or rabies.
To far so good. I have tried to be succinct in describing the immune system, I have in fact barely touched on it.
The evolutionary interplay, in development terms, between immune systems and their foe, is a multi-million-year-old molecular arms race, driven by molecular mutations. An immune system develops antibodies against a virus or bacteria? In time, the bacteria or virus will mutate and develop a new molecular way to overcome the antibodies – often so that the antibodies don’t recognise its target antigens quickly enough, giving the edge once again to invade and colonise. The timeline can be fast, such as with highly mutating RNA viruses that cause cold and flu (link), or extremely slowly such as with DNA viruses like the human papillomavirus (HPV – link). The high mutation rate for the HIV virus is one of the principle reasons it’s been so difficult to develop a vaccine against AIDS for example (link).
This is the fear with SARS-CoV-19. Being new, we know not much. A lot of the work on the COVID-19 virus is so new that it currently remains unpublished. The growing numbers of studies that are published remain mostly as of yet un-peer reviewed. So it can be argued that they are unreliable.
But recent a study on the mutability of SARS-CoV-19 has suggested that it is low, which means that it may be more easy to design an effective vaccine against it (link). To highlight the variability in the data coming through, the authors describe a strain they found in India that has a mutation conferring reduced receptor binding capacity. Although this mutation may weaken the virus, that the mutation occurred at all raises the possibility of others occurring. And this mutation is a worry since it confers a change at the exact site that the majority of vaccines and drug trials are targeting at present.
Another Chinese study reported that the virus had mutated into 2 types, one more severe than the other in terms of infectivity and epidemiological spread (link). This study, it is important to state, has issues, mostly in relation to its small sample size and the small amount of mutations uncovered which may not actually result in a change in viral function (link).
Early in the pandemic (January) bioinformatic computer modelling seemed to suggest that the virus was circulating with low accumulative mutations (link). Recently the same group suggested that the virus may accumulate 24 mutations per year (link). Of course, it is difficult to predict if these mutations might alter the behaviour of the virus (in terms of infectivity, pathogenicity, spread rate, etc). It is important to remember that SARS-CoV-19 is an RNA virus which may mean it has a high mutation rate in common with most other RNA viruses. This is not encouraging. But, it also, rather unusually, has a molecular proof-reading mechanism built into its replication system, much like that of the DNA viruses, and this might prove to suppress the emergence of new dangerous mutations (link).
Now, in May 2020, with far more SARS-CoV-19 genomes sequenced from a wider range of time frames and geographic spreads, more information on the mutation rate is starting to percolate through. A study from the London School of Hygiene and Tropical Medicine have concluded that the mutation rate is low (link). But they add that there are emerging mutations developing independent of each other at different global sites. Two of them alter the protein spikes employed by the virus to attack human cells, which is disconcerting. We know that this virus uses the protein spikes to efficiently attack a wider range of human cell types than previous coronaviruses such as SARS-CoV-1 or common cold viruses. The fear is that mutations can occur that either avoids any new vaccine we manage to develop or makes it far worse than it already is (i.e. increasing the fatality rate) .
The conclusion is as before – the situation is uncertain. It seems to have a low mutation rate, limiting its characteristics to what we currently experience, and raising the hope that a successful treatment may be found and remain effective. But we have detected multiple genetic variations that could change those characteristics, for better or for worse, we are not sure. We have to wait.
Business as usual then.