SARS-CoV-2 mRNA vaccination exposes progressive adaptive immune dysfunction in patients with chronic lymphocytic leukemia
Qin, K.; Honjo, K.; Sherrill-Mix, S.; Liu, W.; Stoltz, R. M.; Oman, A. K.; Hall, L. A.; Li, R.; Sterrett, S.; Frederick, E. R.; Lancaster, J. R.; Narkhede, M.; Mehta, A.; Ogunsile, F. J.; Patel, R. B.; Ketas, T. J.; Cruz Portillo, V. M.; Cupo, A.; Larimer, B. M.; Bansal, A.; Goepfert, P. A.; Hahn, B. H.; Davis, R. S.
Show abstract
Chronic lymphocytic leukemia (CLL) patients have lower seroconversion rates and antibody titers following SARS-CoV-2 vaccination, but the reasons for this diminished response are poorly understood. Here, we studied humoral and cellular responses in 95 CLL patients and 30 healthy controls after two BNT162b2 or mRNA-2173 mRNA immunizations. We found that 42% of CLL vaccinees developed SARS-CoV-2-specific binding and neutralizing antibodies (NAbs), while 32% had no response. Interestingly, 26% were seropositive, but had no detectable NAbs, suggesting the maintenance of pre-existing endemic human coronavirus-specific antibodies that cross-react with the S2 domain of the SARS-CoV-2 spike. These individuals had more advanced disease. In treatment-naive CLL patients, mRNA-2173 induced 12-fold higher NAb titers and 1.7-fold higher response rates than BNT162b2. These data reveal a graded loss of immune function, with pre-existing memory being preserved longer than the capacity to respond to new antigens, and identify mRNA-2173 as a superior vaccine for CLL patients.
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