Another round of SARS-CoV-2 booster vaccines are being offered, but will another booster reduce our risk of COVID-19 disease? This is a question on the minds of many, including Dr. Bo Zhang, an Assistant Professor in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Center, Dr. Dean Follmann, the Director of the Office of Biostatistics Research of NIAID, and their collaborators. To help answer this question, the researchers focused on a specific part of our immune response, neutralizing antibodies, that can bind to a virus particle and block infection of cells. “We were eager to see if the [inverse] relationship between neutralizing antibody and COVID-19 [disease] that was convincingly demonstrated in the ancestral era in an unvaccinated population held up during the omicron era following a booster dose in a vaccinated population,” commented Dr. Follmann. The large team of researchers included several from the Fred Hutch-headquartered COVID-19 Prevention Network (CoVPN). The team went on to show in their paper recently published in Nature Communications that even if someone received as many as three doses of SARS-CoV-2 vaccines or became infected with the circulating strain, they still exhibited a boost in neutralizing antibodies following vaccination and reduced risk of COVID-19 disease.
The SARS-CoV-2 vaccines produce neutralizing antibodies that bind to the spike protein on the surface of the virus particle and block infection of cells. Past studies performed early during the pandemic found vaccine-induced, spike-specific binding and neutralizing antibodies as correlates of protection against COVID-19 disease. In other words, more of these spike-specific antibodies produced following vaccination meant less risk of COVID-19 disease. Since the vaccination status—one or more boosters received—or SARS-CoV-2 infection history may alter this correlation, researchers wanted to perform these analyses again to determine if measuring antibody responses following vaccination remained a good determinant of protection against COVID-19 disease. “We found that antibody measured after the booster dose generally correlated with Omicron COVID-19 and the effect was similar in those previously infected and never infected,” stated Dr. Follmann. “Jerry Sadoff had coined the memorable term `variant-invariant correlate’. Such a correlate would have the same curve linking neutralizing antibody to protection against COVID-19 whether it was ancestral antibody against ancestral COVID-19 or omicron antibody against omicron COVID-19. Our data, coupled with an observational study, showed similarity of the ancestral and omicron curves where they overlapped.” Together, this means that everyone benefited from an additional vaccine dose, irrespective of prior infection or vaccination history for the later wave of omicron variant circulation.
“While the project was a huge undertaking it was gratifying to work with such an outstanding team of scientists,” shared Dr. Follmann. “I felt our strengths complemented each other and we worked together very well.” These findings also help design future vaccine strategies. Dr. Follmann summarized, “Our results support the continued licensure of variant vaccines using small and quickly run immunogenicity studies that show an increase in variant neutralizing antibody.” This plan will help to select effective vaccines that protect against circulating SARS-CoV-2 variants by using neutralizing antibodies following vaccine boosts as an indicator of protection against COVID-19 disease.
The spotlighted research was funded by the National Institutes of Health, Administration for Strategic Preparedness and Response, and Biomedical Advanced Research and Development Authority Contracts.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Drs. Bo Zhang, Holly Janes, James Kublin, Lawrence Corey, Peter Gilbert contributed to this work.
Zhang B, Fong Y, Fintzi J, Chu E, Janes HE, Kenny A, Carone M, Benkeser D, van der Laan LWP, Deng W, Zhou H, Wang X, Lu Y, Yu C, Borate B, Chen H, Reeder I, Carpp LN, Houchens CR, Martins K, Jayashankar L, Huynh C, Fichtenbaum CJ, Kalams S, Gay CL, Andrasik MP, Kublin JG, Corey L, Neuzil KM, Priddy F, Das R, Girard B, El Sahly HM, Baden LR, Jones T, Donis RO, Koup RA, Gilbert PB, Follmann D; United States Government (USG) COVID-19 Immune Assays Team; Moderna, Inc. Team; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE) Team; USG/CoVPN Biostatistics Team. 2024. Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial. Nat Commun. 15(1):7954.
Science spotlight writer Annabel Olson is a postdoctoral research fellow in the Nabet lab at Fred Hutchinson Cancer Center. Her research focuses on studying the mechanisms that drive cancer development for both genetic and virus-associated cancers. A key tool in her research is the use of targeted protein degradation to dissect dysregulated signaling pathways in cancer and to double as a relevant pre-clinical therapeutic platform.
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