With local transmission of the Delta variant now present, do we have a fighting chance?
Dr. Edsel Maurice T. Salvana
Just as many countries were starting to relax their pandemic restrictions, COVID-19 threw more curve balls. Rapid vaccination success stories like Israel, the UK, and the US have had to scale back their reopening plans as the Delta variant took over. Countries that were doing their best to vaccinate, like Chile and Indonesia, suddenly saw a horrific surge of infections reminiscent of the bloodbath in India.
We know the variants of concern may be more transmissible, deadlier, or more vaccine resistant. Partially vaccinated people have gotten infected and hospitalized. Even fully vaccinated people have had occasional breakthrough infections, especially with the new variants. The vaunted over 90 percent vaccine efficacy against symptomatic disease of the Pfizer vaccine against the original SARS-CoV-2 virus is now down to 64 percent against the Delta variant, according to preliminary data from Israel. More than one third of patients who sought medical care for COVID-19 in the UK have had at least one vaccine dose. There was much less breakthrough infection, however, lower than 10 percent, for fully vaccinated people.
We have heard of breakthrough infections in Indonesia and Thailand, with some healthcare workers succumbing to their illness. After some unbalanced reporting by Western news outlets questioning the efficacy of Chinese vaccines, it has become clearer that many of these breakthrough infections are mild. Breakthrough infections are less common among fully vaccinated individuals, and deaths are extremely rare compared to those who were not vaccinated.
In the Philippines, the Food and Drug Administration has released preliminary data from over 1.6 million healthcare workers fully vaccinated with Sinovac. Only 33 had breakthrough infection, almost all of them with just mild symptoms. There were zero deaths among those who completed the recommended doses.
Why is there so much variability among the vaccines when it comes to variants? Do we need to mix vaccines and/or add boosters? Do we need “better” vaccines?
Vaccine efficacy has always been a moving target. Early on, vaccine developers had to decide what vaccine efficacy targets were most feasible. The most important outcome for these vaccines in a pandemic emergency is the prevention of severe disease and death. The two other desirable outcomes are the prevention of symptomatic disease, and the prevention of transmission.
The immune response to vaccines includes the generation of antibodies, cell-mediated immunity, and memory cells. Among these three, antibodies are the easiest to measure, and are the most familiar to lay audiences. The protection that comes from antibodies is, however, among the easiest to misunderstand and this is also why many people are inappropriately calling for booster shots without understanding the natural behavior of antibodies and the rest of the immune system.
Antibodies are proteins that the body makes against a specific target. Antibodies are made by immune cells called B-cells, which are like factories of antibodies. Antibodies are like little guided missiles that seek out a pathogen and attach to them. Cell-mediated immunity produces immune cells called cytotoxic T-cells. These cells act like vigilant soldiers that inspect the body’s cells to see if any have been invaded by a pathogen. If the cytotoxic T-cell finds an infected cell, it destroys these infected cells along with the infecting organism.
When a virus or bacterium gets in, cells called macrophages can pick up pieces of the virus or bacterium and present it to another cell called a T-helper cell. The T-helper cell is a kind of coach of the immune system, which activates different parts, including B-cells. B-cells make antibodies, and cytotoxic T-cells which seek and destroy pathogens that are hiding inside the body’s cells.
Against bacteria that wreak their havoc outside human cells, the body prefers to make antibodies that latch on to these bacteria and slow them down. The antibodies also act as “tags,” which alert white blood cells called neutrophils to phagocytose, or eat, the bacteria. During a bacterial infection, the body makes lots of neutrophils (the white blood cell count goes up), which get rid of the bacteria. Neutrophils can recognize bacteria on their own, but the antibodies make the neutrophils much more potent. The antibodies also activate another arm of the immune system called complement, which pokes holes into the cell wall of bacteria.
Against viruses, which live and multiply inside cells, the body still makes antibodies, but these only work when the viruses are outside the host cells. When the viruses are inside the host cells, the cytotoxic T-cells have to hunt them down. Cytotoxic T-cells have receptors that can tell if a virus is hiding inside a host cell.
Antibodies, particularly neutralizing antibodies which block virus attachment to host cells, are important in stopping the spread of viruses to other cells and to other people. Once the viruses have established infection, however, the more important immune response to prevent severe infection is the cell-mediated cytotoxic T-cell response.
When the body sees a new infectious agent, it takes a bit of time to make antibodies. In the meantime, your innate immune system—neutrophils, macrophages, natural killer cells—try to take out the offending organism with varying degrees of success. The helper T-cells are also triggered and begin to activate antibody production and cytotoxic T-cell production proportionate to what is needed. If it’s a bacterial infection you usually get more antibodies and less cytotoxic T-cells. If it’s a virus, there is more cytotoxic T-cell response and less antibody response.
In addition, the body generates two types of memory cells—memory T-cells and memory B-cells. Memory B-cells can quickly make specific antibodies against a past invader. Memory T-cells can quickly mobilize cytotoxic T-cells against an organism it has seen before. This makes it easier for the body to mount an immune response if it sees the pathogen again.
After the first infection, antibody levels go down naturally over time because they are no longer needed. If the same infectious agent comes back, the memory cells generated from the first infection will result in a much faster ramp up of antibodies and cytotoxic T-cells and will get rid of the infection much faster.
The first dose of vaccination against a virus like COVID-19 simulates the first infection, and the second dose is like a second infection to boost the immune responses and memory cells. It takes longer for the body to make antibodies and mount a T-cell response with the first dose, while the second dose reinforces the response and quickly increases the antibody and cytotoxic T-cell responses.
If there are no further booster doses or exposure to the actual virus, the antibody levels naturally go down. That does not mean the vaccine is no longer working. It just means that the body is conserving its resources. If there is re-exposure, then the memory cells will start making antibodies and cytotoxic T-cells very fast. Therefore, falling antibody levels do not necessarily mean that a booster is needed. Memory B-cells and T-cells can potentially persist for years and can continue to protect even without any boosters. This is why actual clinical data, apart from measuring imperfect antibody levels, is needed to ascertain whether boosters are really necessary and when they need to be given. Laboratory data don’t necessarily reflect protection in real life.
Variants with mutations can become less susceptible to antibodies made in reaction to the original virus, whether by natural infection or by vaccination. This is especially true when mutations affect the spike protein, which the virus uses to attach to host cells to infect them. The impact of these mutations is less certain for cytotoxic T-cell responses, since cytotoxic T-cells use other markers to recognize infected cells. Real life observations show that while vaccine efficacy against symptomatic disease has indeed decreased, the protection against severe disease and death remains very high for all the vaccines. This is consistent with continued robust cell-mediated immunity form cytotoxic T-cells, despite decreased neutralizing antibody activity.
This means that all our vaccines will continue to save many lives, especially among the most vulnerable. We cannot completely rely, however, on vaccines to stop transmission of COVID-19 variants because these are becoming less susceptible to antibody neutralization. The best way forward to get on with our lives is to still use vaccines as a major part of our armor. These, however, may not be enough for complete protection, and we need to enhance this armor with face masks, face shields and physical distancing. This should continue at least until most people are vaccinated to prevent more deaths among the unvaccinated. It will also decrease the risk of the virus mutating further.
If we use all the tools available to us—vaccines, public health standards, strict border control—we will still be on track to have a happier Christmas. Whether it is with masks or not is still up in the air, but at least everyone will be present and no one else will have to die from COVID-19.