New Study Encourages Tailored Vaccination Strategies for Enhanced Protection

A study by a nationwide collaborative group including Larner scientists Mary Cushman, M.D., M.Sc., University of Vermont Distinguished Professor and co-director of the Vermont Center for Cardiovascular and Brain Health; Russell Tracy, Ph.D., University of Vermont Distinguished Professor and director of UVM’s Laboratory for Clinical Biochemistry Research; Margaret Doyle, Ph.D., associate professor of pathology and laboratory medicine and co-director of the Laboratory of Clinical Biochemistry; and Rebekah Boyle, M.S., senior research technician, Laboratory for Clinical Biochemistry Research, was recently published in Nature Communications. Titled “Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study,” the study explored how the human body responded to mRNA COVID-19 vaccines—such as BNT162b2 (PfizerBioNTech) and mRNA-1273 (Moderna). Both vaccines work by helping the body produce antibodies against the COVID-19 virus’s spike protein, but the study team found that the efficacy of the vaccines varied among subjects.

The study sample, which consisted of 6245 twice-vaccinated participants in total, was pulled from 14 long-term, NIH-funded prospective cohort studies, the Collaborative Cohort of Cohorts for COVID-19 Research (C4R). This meta-cohort, consisting of multi-ethnic American adults, considered a wide array of factors that might influence anti-S1 antibody levels, such as age, gender, weight, smoking, diabetes, lung disease, and which vaccine the subjects received. Cushman, who is also a UVM Cancer Center member, and Tracy, along with a team of researchers—including Larner colleagues Boyle and Doyle—found that individuals over the age of 65, men, those with higher weight, smokers, diabetics, and those with a history of emphysema tended to have lower antibody levels. To contrast, subjects who had been diagnosed with COVID-19 previously—particularly those with COVID-19 severe enough to lead to hospitalization—had significantly higher levels of anti-S1 than other groups in the study. Surprisingly, those who had taken the Moderna vaccine also reported a significantly higher level of anti-S1 than the PfizerBioNTech recipients.

The C4R investigation took place over the course of 18 months, from February 2021 to August 2022. The Larner team developed innovative methods to send blood collection kits and instructions directly to participants across the United States, who returned their own samples by taking a finger stick, dripping it on filter paper, and mailing it to Vermont. The “dried blood spots” were used to measure viral serology, including anti-S1 antibodies, at the Wadsworth Center State Department of Health in Albany, New York. S1 antibodies are produced by infection or vaccination. Measurements used Luminex-based microsphere immunoassays, a sophisticated laboratory technique used to detect and quantify specific proteins, such as antibodies, in biological samples like blood.

Previous investigations into vaccine effectiveness primarily relied on data from clinical trials or specific groups, such as healthcare workers or residents of long-term care facilities. In the United Kingdom, where the AstraZeneca vaccine was widely administered (by contrast to the United States), a population-based study revealed lower rates of antibody response post-vaccination among older adults, males, and individuals with underlying health issues. The new C4R study stands out for its comprehensive approach, utilizing meticulously collected pre-pandemic and pandemic-era risk factor data, and blood samples collected during the pandemic from racially and ethnically diverse cohorts in the United States. This approach offers a more nuanced understanding of vaccine response, particularly in comparison to prior studies that lacked detailed information on participants’ pre-existing health conditions.

Tracy stated, “I’m so proud of our lab’s team, especially lead technician Danielle Parent, who developed the methods and training materials to get the dried blood spots from over 20,000 people safely to Vermont, which allowed the study measurements.”

The study underscores the critical importance of COVID-19 vaccination in preventing illness from the virus. “Findings suggest the idea of a nuanced approach to vaccination, where certain population segments with weaker immune responses might need more frequent boosters or higher vaccine doses,” Cushman said. The Larner scientists and the entire C4R team are continuing efforts to understand risk factors for COVID-19, general health effects of the pandemic, and the health consequences of COVID-19.