yesSeveral highly effective vaccines have been developed at unprecedented speed to combat the COVID-19 pandemic. During phase 3 clinical trials, mRNA vaccines had 94% to 95% vaccine efficacy in preventing symptomatic infections. After launch, real-world evidence showed that mRNA vaccines provided ~90% effectiveness against infection. Then came the variants. Wave after wave of new variants, with increasing transmissibility and ability to escape existing immunity, challenge the ability of vaccines to prevent infection and transmission. The effectiveness of a primary series of mRNA vaccines (two doses) in preventing hospitalization and death is also being undermined by these highly immunoevasive variants. Vaccine-mediated protection became shorter, especially with the appearance of Omicron variants. People look at this data and wonder, what’s the point of getting vaccinated if they don’t prevent symptomatic infections and the protection doesn’t last? Well, expecting strong protection from just the primary series of any vaccine is unreasonable, and probably always was, but somehow society has set the bar too high for what is considered an acceptable number of doses for COVID-19 vaccines. Instead, we must understand that we are going to receive reinforcements for the foreseeable future and appreciate its benefits.
Vaccines against other infectious diseases are given in multiple doses. Many of our childhood vaccines require multiple doses: 5 doses for (diphtheria/tetanus/pertussis), 4 doses (Haemophilus influenzae type b, pneumococcal conjugate, inactivated poliovirus), or 3 doses (hepatitis B) are commonly given before the age of 18 years. These doses are necessary and not considered optional to achieve immunity. In adulthood, many of these vaccines require regular booster doses to maintain immunity. The influenza virus requires annual doses of vaccination for all ages. However, people don’t complain about having to get the 60th dose of the flu vaccine. We should think of COVID-19 vaccines in the same way.
Why do we need booster doses? The primary series of vaccines kick-starts the immune response by engaging lymphocytes, white blood cells that detect specific characteristics of the pathogen to expand in number and receive instructions to eliminate the pathogen. Most of these cells disappear over time, except for a small subset of cells that the body retains for future use. These “memory cells” are responsible for long-lasting immunity against a given pathogen. What boosters do is stimulate these memory lymphocytes to rapidly increase in number and produce even more effective defenders. Boosting also selects for B cells that can secrete antibodies that are even better at binding to and blocking infection and spread of the virus.
The primary series can be thought of as the secondary school of lymphocytes, where naive cells receive basic instructions to learn about the pathogen. The boosters are like a university where the lymphocytes are further educated to be more skilled and mature, to fight off future infections. Periodically, these college grads need to be refreshed with more booster doses given later in life. This is the case for all vaccines. Booster doses give your immune system the education it needs to prevent serious illness from infection.
COVID-19 vaccines also need booster doses for the same reasons. We need to educate, maintain, and enhance T and B cell responses to prevent serious disease. The boosters provide significant benefits to people who received the primary series in preventing hospitalization and death. In the US in April 2022, people over the age of 50 who did not receive the vaccine, only the primary series (no booster dose), or a booster dose had a 38x, 6x, or 4x higher risk of death , respectively. of COVID-19 compared to those with two or more booster doses. During Omicron’s predominant period, the booster dose provided protection against hospitalization even in previously infected persons, whether they were older (>65 years) or younger (<65 years). Among children and adolescents, a primary series (two doses) of vaccination was less effective in preventing emergency department and urgent care encounters associated with COVID-19 during the Omicron wave compared to the Delta period. Immunity also declines with time since primary vaccination. No significant protection was detected more than five months after a second dose of vaccine among adolescents aged 16 to 17 years. However, a third booster dose restored the vaccine's effectiveness to 81% in this age group. Thus, there is a clear benefit of a booster dose across a wide range of age groups studied to date.
Can booster vaccination be improved in the future? Absolutely. We need improved boosters that can provide longer-lasting protection, are effective against variants we encounter in the future, and do a better job of preventing infection and blocking transmission. For example, booster-induced immune protection declines over 4 to 6 months during the current period of Omicron. We need vaccine strategies that provide longer-lasting protection. Boosters are now being developed to match Omicron’s BA.5 variant in circulation, which should provide better protection than boosters based on the original strain. However, due to the rapidly mutating nature of SARS-CoV-2, we will need boosters in the future that can provide coverage against not only existing but future variants as well.
There is a need to look for boosters that work against a wide range of SARS-CoV-2 variants, now or in the future, as well as other coronaviruses that may cause future pandemics. Coronaviruses have made the jump from animals to humans multiple times in history, resulting in pandemics. Vaccines that can broadly protect against a wide range of coronaviruses will also prevent future pandemics. In addition, future boosters should be administered as nasal spray vaccines to provide local mucosal immune protection, capable of reducing infection and transmission at the portal of entry of the virus and reducing the prolonged risk of COVID. Ultimately, we need booster strategies that can be more easily implemented around the world and have higher uptake and acceptance rates to provide the immune protection everyone needs. An over-the-counter nasal spray booster can bring us closer to that goal.
Researchers and industry are working as hard on developing next-generation vaccines as they have on our current vaccines, which have saved more than 14 million lives during the pandemic. But for now, take the booster doses you are eligible for to keep your immune system educated and up to date so that it has the best chance of protecting you from COVID-19 in the coming winter season and so that we can prevent the enormous loss of life. experienced last winter with over 300,000 people dying in the US from a disease that is preventable with today’s boosters.
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