COVID-19 vaccine's effectiveness diminishes with age, UTSW research shows – UT Southwestern

A new study underscores the need for boosters and variant-specific vaccines in older adults
DALLAS – Nov. 29, 2022 – The Pfizer-BioNTech COVID-19 vaccine limits transmission, hospitalization, and death from COVID-19 even among patients infected by variants of the virus, but the effectiveness of antibodies it generates diminishes as patients get older, according to a study by UT Southwestern researchers.
“The fact that these antibody functions decrease with age is one reason why the elderly are still more susceptible to severe illness with COVID-19 and highlights the need to develop different approaches for older, vulnerable individuals,” said Lenette Lu, M.D., Ph.D., Assistant Professor of Internal Medicine and Immunology in the Division of Infectious Diseases and Geographic Medicine, and lead author of the paper published in Cell Reports.
The vaccine, approved by the U.S. Food and Drug Administration in August 2021, contains a piece of mRNA encoding the SARS-CoV-2 spike protein, which the virus uses to infect human cells. Initial studies of the vaccine focused on how it led to the generation of antibodies that could prevent SARS-CoV-2 from entering cells, neutralizing the virus before it could cause disease. 
The emergence of new variants, including Delta and Omicron, left the vaccine less effective at neutralizing SARS-CoV-2 and resulted in increased rates of infection. However, vaccinated individuals, even when infected with COVID-19, continued to be protected against severe disease and death. 
To understand how vaccines protect people without completely neutralizing the virus, blood samples were analyzed from 51 adults, ranging in age from 21 to 82, who had not been infected previously with COVID-19 and who each received two doses of the Pfizer-BioNTech vaccine between December 2020 and February 2021. From the samples, the researchers isolated antibodies specific to the SARS-CoV-2 spike protein.
The team showed that the antibodies generated in response to the vaccine were effective at neutralizing the original version of SARS-CoV-2 that emerged in 2019 but, as expected, were not as effective against the Delta and Omicron variants. In addition, the researchers found that these antibodies led to the activation of immune cells that can carry out a variety of antiviral effector functions after infection.
“In other words, even if an antibody is less able to prevent variants of a virus from infection, it can still block the development of symptoms, disease severity, and spread from one person to another,” said Dr. Lu.
These antibody activities and functions differed by age, with people under 65 carrying significantly more of the activities and functions compared to those over 65. Dr. Lu’s team discovered these observations could be attributed to different sugars attached to the antibodies. With age, these sugars change and antibody functions diminish.
The data suggests that boosters and updated vaccines are more important for older adults. In addition, as new variants of SARS-CoV-2 emerge, a better understanding of how to make vaccines that are effective at preventing disease in addition to infection is important.
“Beyond COVID-19, all viruses and bacteria that infect us change over time,” said Dr. Lu. “If we understand how antibodies protect us despite these changes, then we can enhance the durability of preventive clinical tools such as vaccines.”
Other UTSW researchers who contributed to this study include Pei Lu, Ye Jin Kang, Micah Thornton, Chanhee Park, and Daehwan Kim.
This study was supported by grants from the M.J. Murdock Charitable Trust, Oregon Health & Science University (1018784), the OHSU Foundation, the National Institutes of Health (R011R01AI141549-01A1, R01AI145835, T32HL083808), the Burroughs Wellcome Fund UT Southwestern Training Resident Doctors as Innovators in Science, and the UT Southwestern Department of Internal Medicine and Disease-Oriented Scholars Award.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 24 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.
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