Some studies suggest that the protection offered by currently authorized COVID-19 vaccines against contracting a SARS-CoV-2 infection and developing severe disease starts to wane after a few months. A booster shot can counter this decline in immune protection.
The Decline in Immunity against SARS-CoV-2
The decline in immunity against SARS-CoV-2 is associated with a gradual decrease in neutralizing antibody levels. A recent phase 2, randomized clinical trial assessed the safety and effectiveness of seven different vaccines as the third booster dose after two initial doses of either the Pfizer-BioNTech or Oxford-AstraZeneca vaccine. All vaccines except one were effective in enhancing the antibody response at 28 days after the booster.The inflammatory side effects caused by the vaccines were tolerable and generally involved headaches, fatigue, and injection site pain.
This decline in immunity against SARS-CoV-2 may have contributed to the recent rise in COVID-19 cases in the United States and Europe. However, COVID-19 vaccines continue to confer a reasonably high degree of protection against severe disease and death at least 6 months after vaccination.
The evidence of waning protection against the Delta variant of SARS-CoV-2 led health agencies in the U.S. and Europe to authorize the use of boosters for older inpiduals and those at higher risk of developing COVID-19 earlier this year.
Heterologous Dosing
The recent rise in COVID-19 cases has prompted public health agencies in the U.S. and some European countries to expand the eligibility for booster shots to all inpiduals over the age of 18 years.
Moreover, the Centers for Disease Control and Prevention (CDC) allow inpiduals to choose a different vaccine for their booster shot than the one they received for their initial two doses.
Such a mix-and-match approach to vaccination, otherwise known as heterologous dosing, may be advantageous over a homologous schedule, which involves the use of the same vaccine for the prime and the boost.
Previous studies that used heterologous dosing for the initial two doses suggested that this approach may provide greater protection against a SARS-CoV-2 infection than a homologous schedule.
A recent randomized clinical trial called COV-Boost assessed the safety of and immune response generated by heterologous and homologous booster schedules in inpiduals who received two initial doses of either the Oxford-AstraZeneca vaccine or the Pfizer-BioNTech vaccine. The study found that both schedules were effective in boosting immune response at 28 days after the booster shot and produced well-tolerated side effects.
COVID-19 Vaccines and Immunity
The Oxford-AstraZeneca and Pfizer-BioNTech vaccines deliver the genetic information that encodes for the SARS-CoV-2 spike protein to human cells, enabling them to produce this protein. The production of the coronavirus spike protein by cells in the human body generates an immune response involving antibodies and T cells. Neutralizing antibodies produced by B cells, which are a type of white blood cell, bind to the virus to disrupt its ability to infect human cells. Some studies have suggested that neutralizing antibody levels tend to predict the degree of protection against SARS-CoV-2 infection.
The levels of neutralizing antibodies against the wild-type SARS-CoV-2 tend to wane a few months after the second dose of the vaccine. Moreover, vaccinated inpiduals tend to produce lower levels of neutralizing antibodies against variants of concerns, such as the Delta variant. These variants of concern can also escape neutralization by antibodies in vaccinated inpiduals. In other words, the decline in the neutralizing antibody response may result in limited protection against SARS-CoV-2 infection.
Vaccination also results in the generation of memory immune cells that persist despite the decline in neutralizing antibodies. These memory cells form the second line of defense and prevent severe disease after the infection has occurred. The presence of memory T cells, which are another type of white blood cell, can help launch a rapid T cell response after infection. T cells help eliminate infected cells to prevent the spread of the infection. So, early activation of T cells due to vaccination plays a critical role in preventing severe COVID-19 and death. Unlike the relatively drastic decline in neutralizing antibodies, the T cell response remains mostly intact.
Studies have suggested that COVID-19 boosters can help enhance immunity against the Delta variant and prevent breakthrough infections.
Omicron Variant
The Omicron variant of COVID-19 has been called a variant of concern by WHO based on the evidence that it has several mutations that may have an impact on how it behaves. There is still substantial uncertainty regarding Omicron and a lot of research underway to evaluate its transmissibility, severity and reinfection risk.
Two doses of a Covid vaccine are not enough to stop catching the Omicron variant. Early analysis of UK Omicron and Delta cases showed the vaccines were less effective at stopping the new variant.But a third booster prevents around 75% of people getting any Covid symptoms. One of the main concerns since the heavily-mutated Omicron variant first emerged was that it would make vaccines less effective.
The UK Health Security Agency analyzed data from 581 Omicron cases and thousands of Delta cases to calculate how effective the vaccines were against the new variant. The showed a dramatic drop in effectiveness for the Oxford-AstraZeneca vaccine and a significant drop off for two doses of Pfizer. The 75% protection against Covid symptoms after a booster is not as high as against previous variants.
Vaccines are still likely to offer good protection against severe Covid that needed hospital treatment. However, an Omicron wave could be problematic even if it was milder. A large and sudden wave could lead to everyone who is still vulnerable needing hospital care at the same time.
The vaccines were all developed to fight the first form of the virus that emerged two years ago. The protection you're left with after the third dose is bigger, broader and more memorable than you had before.
Fighting coronavirus is something your immune system has to learn. One option is to figure it out on the job when you encounter the virus for real. Vaccines are more like a school - a safer environment to further your immune system's Covid education.
The first dose is the primary school education that nails the fundamentals. Your second and third doses are comparable to sending your immune system to secondary school and then university to dramatically deepen its understanding. It's not just repeating primary school over and over. The immune system is left with a richer knowledge and understanding of the virus.
A booster is like a university education for the immune system. Antibodies are a major beneficiary of this education. These are the sticky proteins that attach themselves to the outside of the coronavirus. Neutralizing antibodies can gum up the virus so it can't invade your cells.
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