A recent study conducted by researchers in London suggests that the timing of the booster shot plays a large role in the effectiveness of the Oxford AstraZeneca vaccine. The study found that efficacy against the virus was higher as the time between doses increased. The study found no evidence that one shot of the vaccine offered less protection than two, and protection from the first shot of the ChAdOx1 nCoV-19 vaccine stayed consistent for the first three months after vaccination. A single dose protected against symptomatic cases in 90 days but was not as helpful with symptomatic cases. These findings are important because they show evidence for the effectiveness of two doses of the vaccine of the original booster.
The study was conducted by Merryn Voysey, Sue Ann Costa Clemens, Shabir Madhi, Lily Weckx, and Pedro Folegatti. It was conducted in London in early 2021 and was published in The Lancet in March 2021.
This topic is important in general because COVID is a virus that has impacted our lives since the end of 2019. The symptoms range from mild to severe and it has caused millions of deaths and health problems. Symptoms include fever, chills, coughing, shortness of breath, and body aches, and it is spread through droplets & particles in the air
In the United States, the Center for Disease Control or CDC reported 40,000,000 cases in the last 30 days. 75.2% of adults have at least one vaccine and community transmission is high. There have been 649,000 deaths in the last 30 days in the United States. In the United Kingdom, there have been 7,000,000 cases and 133,000 deaths. In Brazil, there have been 20,900,000 cases and 584,000 deaths. In South Africa, there have been 2,800,000 cases and 84,000 deaths.
When germs/viruses invade our bodies, they multiply and cause illness. Blood contains red cells which carry oxygen and white blood cells which fight infection. Macrophages are white blood cells that digest germs and dead cells. They leave parts of germs which are called antigens. Antibodies attack antigens because the body declares them to be dangerous. B-lymphocytes are defensive white blood cells and they produce antibodies that attack antigens. T-lymphocytes are also defensive white blood cells. They attack already infected cells, and they are memory cells. It takes days to weeks to use germ-fighting tools to overcome infection. Memory cells attack if the virus comes back.
Vaccines work when the body leaves a supply of memory T-lymphocytes & B-lymphocytes. It takes a few weeks after the vaccine to produce these lymphocytes and you can still get sick shortly before or after the vaccine. There are several types of vaccines. First is the mRNA vaccine, which uses material from the virus to instruct our cells to make harmless proteins for the virus. These cells make copies & destroy genetic material and the bodies recognize protein shouldn’t be there and build T&B lymphocytes to fight the virus if we get infected later. There is also a Protein subunit vaccine that Includes harmless proteins that cause COVID. The body recognizes protein shouldn’t be there & build T antibodies that remember how to fight the virus. Lastly is the vector vaccine. This is a modified version of a different virus. Inside the virus, the shell is material from covid which is called the viral vector. Genetic material instructs cells to make a protein that’s unique to the covid virus and the cells make copies of the protein. Our bodies build T&B lymphocytes to fight viruses.
There are four types of vaccines on the market. The main ones that we will be focusing on today include Pfizer-BioNTech which is two shots twenty-one days apart. If you are immunocompromised, you should have three shots. It is an mRNA vaccine. You are Fully vaccinated two weeks after the second shot. It is 95% effective in those who are sixteen and older and is effective at preventing covid in twelve- to fifteen-year-olds. It is also effective among different demographics. Secondly is Moderna. It is two shots twenty-eight days apart (some immunocompromised individuals should have three). It is also an mRNA vaccine. You are fully vaccinated two weeks after the second shot. It is 94.1% effective in adults eighteen and over. It is effective among different demographics. However, there is no data for real-world conditions. The Johnson and Johnson/Janssen is a one-shot vaccine. It is a viral vector vaccine. Many people have reported fainting after vaccination (653 reports among eight million doses). Blood clots in seven per one mill vaccinated women eighteen to forty-nine. With women over fifty and men in general, clots are very rare. You are fully vaccinated two weeks after the shot, and, in clinical trials, the vaccine was 66.3% effective. The vaccine that the study focuses on is the Oxford AstraZeneca vaccine. It was authorized for emergency use and prioritized for health workers and elderly people (sixty-five and older). It is not recommended for minors. It consists of two doses w/ an interval of eight to twelve weeks between them. The World Health Organization notes additional research to understand long term protection after a single dose and the efficacy of this vaccine is 63.09%
A booster shot is a dose of the vaccine that is given after the initial series when it is thought that the immune response has begun to wane over time. These shots “boost” the immune system. Some argue that a booster shot is needed to maximize the effect of the covid virus. Booster shots retrain the body to fight itself against the virus. These can be administered weeks, months, or years after the initial series. For COVID, it is currently recommended to get the booster eight months after the initial shot of the two-dose vaccines. There is a difference between a third shot and a booster. A third shot is for people who are immunocompromised and don’t build enough protection against the virus. Getting another dose can help build more protection. The CDC recommends moderately/severe immunocompromised people receive a third dose 28 days after the initial series. A booster is another dose of vaccine given to someone who built enough protection, but it decreased over time.
There is some debate over whether widespread booster shots would help to flatten the curve. The US gives boosters to immunocompromised individuals or healthcare workers. This is less controversial because benefits are seen and not many doses are required for this demographic. However, there is still not enough evidence that boosters are needed or will control the pandemic. The vaccines seem to be working well. The dose spacing was not chosen for long immunity, but to speed up clinical testing, so a boost a few months later may be ideal. Another question is whether we should prioritize vaccinating the unvaccinated? High-risk people worldwide do not have their first dose. Boosters are not a good way to use the limited global vaccine supply. If everyone in first-world countries received the booster, 1 billion doses would be used up. When countries stock up, it disrupts the system. In the United Kingdom with 66 million people and who bought 110 million doses, there is 80% of the population vaccinated. At-risk people should receive boosters first. Scientists say that one booster at the right time could provide long-lasting immunity. It is not known who will need a booster yet, how long after their dose, or which combination works best.
The study was conducted because the Oxford AstraZeneca vaccine was authorized for emergency use in the United Kingdom after efficacy results from 131 symptomatic cases. The vaccine rollout in the UK accounted for two doses of the vaccine 12 weeks apart, which was a very controversial policy.
The researchers were trying to find out: Does the efficacy of the vaccine depend on the length of the prime-boost interval?
Their hypothesis was that the vaccine is more effective with a longer interval between doses and that a single dose is effective within the first three months.
The study responded to prior research and questions whether the UK administer two doses 12 weeks apart because the vaccine was approved for emergency use in the UK because of efficacy results from over 100 symptomatic cases. Also, the immunogenicity and efficacy of a single dose vaccine. The study did have human subjects. There were three single-blind randomized trials in the UK, Brazil, and South Africa. There were three phases. First was the UK phase used subjects eighteen to fifty-five years of age. The second UK phase & Brazil used subjects who were eighteen and older and South Africa used subjects who were eighteen to sixty-five. It is interesting that the age stopped at sixty-five, because older people are at a greater risk to the symptoms of COVID, and because AstraZeneca was aimed at those sixty-five years and older. Brazil focused on healthcare workers and immunocompromised people. These methods were not based on another study. Participants had to be symptomatic. In the UK, asymptomatic infections were measured using nose and throat swabs. Even if subjects tested positive, they were not contacted for the study.
The study found no evidence that one shot of the vaccine offered less protection than two, and protection from the first shot stayed consistent for the first three months after vaccination. A single dose protected against symptomatic cases in 90 days but was not as helpful with symptomatic cases. This shows that we may not even need the booster, but for certain populations, it can be beneficial. This study provides policymakers with information on the optimal dose interval. These findings provide a basis for verification of the data that supported the emergency use authorization of the vaccine in the UK and provides strong evidence that supports the efficacy of two doses of the vaccine.
There were seven deaths (unrelated to vaccination but still worth noting; two in the AstraZeneca group and five in the control). There was one COVID death in the control group. The methods make sense. This study could be repeated in the future with a different vaccine [or different demographics]. The long-term effects are unknown. The study was not designed to determine if vaccine efficacy differed by dose interval and presence of data of varying intervals because this was a large clinical trial conducted during a pandemic. The study stated that there are “post-hoc exploratory analyses only with the potential for multiple sources of bias.”
This study could be improved in the future? Studies were not designed to establish if efficacy differed by dose interval. They could include the length of follow-up after the second dose as follow-up is usually longer with those who received the booster early and have a shorter prime-boost interval. The participants were a mixture of events before their booster dose and participants who did not receive the booster. The demographics could also be equalized. Most of the subjects were men- this is problematic because if this was done for J&J, the vast majority of those who passed away were women and women had the most health issues related to blood clots. Participants who got the booster were younger in this study, and less were white compared to those who did not get a booster dose) findings show effectiveness at reducing disease and advantages over some programs.
It is worth noting the funding that contributed to this project. Funded by National Institute for Health Research (NIHR), Vaccitech, Janssen, GlaxoSmithKline, UK Research and Innovation, Bill and Melinda Gates Foundation, Lemann Foundation, Rede D’or, Brava & Telles Foundation, Duke Human Vaccine Institute, SAMRC. Many of the authors worked to develop the vaccine and Oxford entered into a partnership with Astra Zeneca.
There is an ongoing study of correlates of protection, as one has yet to be identified for the COVID vaccine; the data in this study suggests that humoral immunity could play a role in the relationship between antibody levels and efficacy. Anonymous participant data will be available when the trial is completed and after approval, data can be shared after an agreement is signed.
The FDA recently made a big announcement regarding the Pfizer booster shot, and this news clip details what they said:[News Clip]
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