There are serious disputes about the strategies for Covid-19 vaccination. It will take time to produce sufficient quantities of each vaccine, so some countries – notably the United Kingdom – have decided to delay the second dose.
“Pretend that nothing has happened,” is the advice of experts on how to behave after a single dose of any Covid-19 vaccine. And here’s why.
When 85-year-old Colin Horsman was admitted to Doncaster Hospital in late December, doctors suspected he had a kidney infection. But shortly thereafter, he contracted Covid-19 – at that time, about one in four people in the hospital with that virus contracted it there. Horseman developed severe symptoms and was eventually placed on a ventilator. He died a few days later.
Hersman’s case may seem typical, but it is no less tragic for that. At the time of this writing, over 90,000 people have died from the coronavirus in the United Kingdom alone. But as Colin Horsman’s son recently told a local newspaper, less than three weeks before his illness, his father became one of the first people in the world to receive the first dose of Pfizer-BioNTech’s Covid-19 vaccine. He was to receive the second dose two days before his death.
In fact, most vaccines require booster doses to maintain their effectiveness. Take, for example, the measles, mumps, and rubella vaccine, known as MMR, which is given to infants around the world to prevent these childhood infections. About 40% of people who received only one dose are not protected against all three viruses, compared to 4% of those who received the second dose. The first group is four times more likely to contract measles than the second. Outbreaks of the disease have been observed in areas where a significant proportion of the population has not received the full MMR vaccine.
“The reason people think boosters are important is that they put you in a completely different mode of fine-tuning your immune response,” says Danny Altmann, professor of immunology at Imperial College London.
When the immune system first encounters a vaccine, it activates two important types of leukocytes. The first are plasma B cells, which are primarily involved in antibody production. Unfortunately, this type of cell is short-lived, so while your body may fill up with antibodies in a few weeks without a second injection, this is often accompanied by a rapid decline in their number.
The role of T cells is to recognize and destroy pathogens. We explain quickly, simply, and clearly what happened, why it matters, and what will happen next. The number of episodes should not be changed. End of story. Podcast advertising.
The second type are T cells, each of which is specifically designed to identify and destroy a particular pathogen. Some of them, memory T cells, are capable of remaining in the body for decades until they meet their target, meaning that immunity to vaccines or infections can sometimes last a lifetime. But there is an important point. Usually, the number of these cells in your body will be small before the second encounter with the infection. A booster dose is a way to re-expose the body to antigens (molecules from pathogens that trigger the immune system) to initiate the second part of the immune response.
“So you have started this process,” says Oltmann. “Now, when you get the booster, you will have more memory T cells. To some extent, this also applies to the number of memory B cells in your body. They will also produce higher quality antibodies. With repeated exposure to the same vaccine or pathogen, the remaining B cells are capable of rapid division, resulting in a subsequent increase in the amount of circulating antibodies.
It will take time to produce sufficient quantities of each vaccine, so some countries – most notably the United Kingdom – have decided to delay the second dose. The second dose also activates the process of “B-cell maturation,” which selects young cells with better receptors for capturing a specific pathogen. This happens while they are still in the bone marrow, where white blood cells are formed, and then they enter the spleen to complete their development. This means that not only will there be more B cells in the future, but the antibodies they produce will be more effective. T cells also multiply rapidly. They are thought to have played a critical role in the current pandemic, protecting some people from developing severe forms of Covid-19. Although the virus may have been circulating worldwide since December 2019, there is evidence that memory T cells may have previously “seen” other coronaviruses, such as those that cause the common cold, allowing them to now recognize Covid-19.
So how effective is a single dose of each of the Covid-19 vaccines? Considering that the British government has decided to delay the second dose of all currently licensed Covid-19 vaccines from 3-4 weeks to 12 weeks, and that Russia is testing a single-dose regimen with the Sputnik V vaccine called “Sputnik-Light,” the answer to this question is extremely important and highly complex. Here is what we know at this time.
According to Pfizer data published in December 2020, the Pfizer-BioNTech vaccine is approximately 52% effective after the first dose.
According to the manufacturer, the Pfizer-BioNTech vaccine is approximately 52% effective after the first dose. Of the 36,523 participants in the third phase of the trial (the final phase of the trial in which people received either two full doses separated by 21 days or a placebo), 82 people in the placebo group and 39 people in the vaccine group developed symptoms of Covid-19 among those who had no evidence of infection.
However, this early protection comes with some important caveats. First, the protection does not take effect until at least day 12 – no difference was observed between the two groups before that time. Second, a single dose is still significantly less effective than two doses. A double dose achieves 95% disease prevention within one week.
But there is another number that has been circulating on the Internet, and surprisingly, some doctors have even talked about it with their patients: the assumption is that the first dose is about 90% effective. And this is where things get a little more complicated.
A similar assessment was made by the UK’s Joint Committee on Vaccination and Immunization (JCVI), which decided to calculate vaccine effectiveness differently. Instead of using all the data on the number of infections, including those in the first few days when the first dose had not yet taken effect, they used only the data from the 15th to the 21st day after the first dose. Using this method, the effectiveness of the vaccine increases to 89%, as it is not influenced by a relatively large number of infections before the vaccine begins to take effect.
If we go further and consider only the first seven days after the second dose (days 21-28) – because the second dose may not have taken effect by then – the efficacy reaches 92%. However, these calculations are at least questionable.
“People are currently carefully studying the graphs in the Pfizer article published in the New England Journal of Medicine, which show that some benefit should be apparent as early as day 14,” says Oltmann. “This is the case when the curves for the placebo group and the vaccine group completely diverge and the number of cases starts to rise in the placebo group. However, it is clear that this is not a direct measurement of the immune response, but rather a rough estimate of the number of infected individuals. Oltmann says he would not advise anyone to consider themselves safe 14 days after the first dose of the vaccine. “The timeline is just a way of saying ‘something is happening,'” he believes.
In Israel, which is leading the way in vaccinating its population, medical experts have warned that a single dose of the vaccine has proven to be “less effective than we thought” and less effective than Pfizer had anticipated. Israel’s government coordinator for coronavirus control, Nachman Ash, said that those who received the second dose of Pfizer’s vaccine showed a 6-12 times increase in antibody levels compared to those who received only one dose.
In the case of the Oxford-AstraZeneca vaccine, things are a little different. In the article published in January, the authors explain that the vaccine provides 64.1% protection after at least one standard dose. This can be compared to 70.4% for those who took two full doses, or surprisingly 90% for those who took a half dose and then a full dose.
The Ebola vaccine is the only one to use the same technology as the Russian vaccine and the Oxford-AstraZeneca vaccine against Covid-19. Meanwhile, based on unpublished data provided to the Committee, it has been calculated that the vaccine prevents approximately 70% of severe COVID cases between three and 9-12 weeks after the first vaccine injection. Because the third phase of the trial included two breaks between the first and second doses, including one of six weeks and a longer break of 12 weeks, it can be said with greater confidence that the first dose can continue to provide some protection for at least several months until a booster dose is given.
According to the company’s filing with the U.S. Food and Drug Administration (FDA), one dose of Moderna’s vaccine can provide 80.2% protection, compared to 95.6% after the second dose (in people aged 18 to 65 years) and 86.4% in those older than 65 years. As with the Pfizer vaccine, all participants in the third phase of the trial received two doses of the vaccine or a placebo within a fixed period of time – in this case, 28 days. As a result, it is not yet known whether a single dose of the vaccine will maintain or diminish immunity.
The CoronaVac vaccine was developed by Sinovac, a biopharmaceutical company based in Beijing. This vaccine is unique in that it has been independently tested in several countries, all with different results. The United Arab Emirates was the first country to estimate its effectiveness at 86%. According to Turkish researchers, the vaccine provides 91.25% protection, while scientists from Indonesia said it was effective at 65.3%, and the Butantan Institute in São Paulo, Brazil, recently announced that the vaccine prevents the development of symptoms in 50.4% of people. Currently, no one has published data on the effectiveness of a single dose – these numbers only apply to two doses 14 days apart.
The results were greeted with some skepticism because they were published in press releases rather than in a peer-reviewed journal, as is customary in the scientific community. Without access to additional information about the test methods and data collected, it is difficult for scientists to independently assess the reliability of the results.
The Sputnik V vaccine was developed by the N.F. Gamaleya National Research Center for Epidemiology and Microbiology in Moscow. As with others, this vaccine is administered in two doses and appears to be 91.4% effective after the second dose – there is currently no publicly available information on the effectiveness of a single dose. Again, these results were not published in a peer-reviewed journal and may be unreliable.
During the first week of vaccination last December, clinic waiting rooms were reportedly half empty. Recently, the Russian government announced the development of a new version of “Sputnik-Light” as a temporary solution to the problem of the original vaccine shortage. The vaccine will be administered as a single dose, although it is unclear how effective it will be.
“I would behave exactly the same as if I hadn’t been vaccinated,” says Oltmann. “I would never let my guard down for anything.” Deborah Dunn-Walters, a professor of immunology at the University of Surrey, is equally clear about how to behave. “There are several reasons for this,” she warns. “First, you will not be completely protected. And second, there is currently no evidence that vaccination completely prevents infection with the virus and its transmission.”
Dunn-Walters explains that the effectiveness of vaccines has largely been evaluated based on whether they prevent the development of symptoms in individuals, rather than the actual infection with the virus. “And we know that the infection can be asymptomatic,” she reminds. There is currently no evidence that one – or even two – doses of any of the existing vaccines will stop the virus from being transmitted to others. “Preclinical studies have shown that immunity is not sufficient after a single vaccination, so two doses are needed,” says Dunn-Walters. Also in the third phase of the trial, there were more antibodies and T cells in the blood after two doses than after a single dose.
It can take weeks to develop immunity, so no Covid-19 vaccine will protect you immediately.
In December, Pfizer CEO Albert Bourla said it would be a big mistake to miss the second dose because it nearly doubles the level of protection. Pfizer and BioNTech also urged caution based on the fact that “there are no data demonstrating that protection is maintained for 21 days after the first dose”. It is quite possible that the protection provided by the first dose will suddenly disappear after this time. This is not surprising given how the immune system normally works.
Reliably estimating the duration of protection from a single dose is further complicated by the fact that all currently approved vaccines against Covid-19 use completely new technology. The Oxford-AstraZeneca and “Sputnik V” vaccines contain modified versions of adenoviruses – a group of viruses that can invade many types of cells and cause a range of diseases, including respiratory infections. While the Oxford version uses chimpanzee adenovirus, the Russian version uses a mixture of two human types. For vaccine production, the virus has been modified so that it is safe and cannot replicate inside cells. It can teach the body to recognize the coronavirus by encoding instructions to recognize its characteristic feature – the spike protein. Although adenoviruses have been used in cancer vaccines and gene therapy for many years, they have only been used once to prevent viral infection – an Ebola vaccine using this method was approved for use in the United States in December 2019.
It is not clear how long the partial protection provided by a single dose of any Covid-19 vaccine will last. The Moderna and Pfizer-BioNTech versions may be even more innovative. Both contain countless tiny fragments of mRNA (messenger RNA) that, like the adenovirus-based vaccine, “synthesize” the spike protein from the surface of Covid-19. These are the only mRNA vaccines ever approved for use in humans, and their efficacy is simply not comparable. Ronald Corley, a professor of microbiology at Boston University, said in a recent interview with the university’s magazine that there are still many uncertainties about these vaccines. For example, it is unclear whether they will work equally well in people of all ages and races, and how long immunity will last.
The CoronaVac vaccine contains inactivated particles of the coronavirus. This method is not new – the concept of using dead pathogens in vaccines has been around since the late 19th century. However, it is still unclear how long such immunity will last, as no vaccine derived from members of this family of viruses has ever been approved for use prior to the pandemic.
Finally, Dunn-Walters emphasizes that it takes time for immunity to develop, so regardless of whether a single dose of any of the Covid-19 vaccines ultimately provides protection, during the first two weeks after receiving the vaccine, your immunity to the virus will be no greater than it was before the vaccine was administered.
Vaccines take time to protect against disease. “In the immune system, there is a part called “innate immunity” that responds immediately,” says Dunn-Walters. It includes physical barriers to infection, such as skin, as well as certain types of white blood cells and chemical signals. But, as the expert explains, this in itself usually does not prevent the disease – and vaccines have no effect on it. “So you need adaptive immunity. However, the problem with adaptive immunity is that, as the name suggests, it adapts to individual threats from pathogens,” Dunn-Walters continued. For vaccines to be effective, they must stimulate the body to produce more immune cells, some of which in turn produce antibodies. “And that takes time,” Dunn-Walters adds. So while the introduction of new vaccines can bring a wave of optimism, it seems that most of us will have to wait a little longer to return to normal life.