Poor antibody response to BioNTech/Pfizer COVID-19 vaccination in SARS-CoV-2 naïve residents of nursing homes

Pannus, P.; Neven, K. Y.; De Craeye, S.; Heyndrickx, L.; Vande Kerckhove, S.; Georges, D.; Michiels, J.; Francotte, A.; Van Den Bulcke, M.; Zrein, M.; Van Gucht, S.; Schmickler, M.-N.; Verbrugghe, M.; Matagne, A.; Thomas, I.; Dierick, K.; Weiner, J. A.; Ackerman, M. E.; Goriely, S.; Goossens, M. E.; Ariën, K. K.; Desombere, I.; Marchant, A.

Background Residents of nursing homes (NH) are at high risk of COVID-19 related morbidity and death and may respond poorly to vaccination because of old age and frequent comorbidities. Methods Forty residents and forty staff members either naive or previously infected with SARS-CoV-2 were recruited in two NH in Belgium before immunization with two doses of 30g BNT162b2 mRNA vaccine at day 0 and day 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD), spike domains S1 and S2, RBD Ab avidity, and neutralizing Ab against SARS-CoV-2 wild type and B.1.351 variant were assessed at days 0, 21, 28, and 49. Results SARS-CoV-2 naive residents had lower Ab responses to BNT162b2 mRNA vaccination than naive staff. These poor responses involved lower levels of IgG to all domains of the vaccine antigen, lower avidity of RBD IgG, and lower levels of Ab neutralizing the vaccine strain. No naive resident had detectable neutralizing Ab to the B.1.351 variant. High and comparable Ab responses were observed in residents and staff previously infected with SARS-CoV-2. Clustering analysis revealed that poor vaccine responders not only included naive residents but also naive staff, emphasizing the heterogeneity of responses to mRNA vaccination in the general population. Conclusions The poor Ab responses to mRNA vaccination observed in infection naive residents and in some naive staff members of NH suggest suboptimal protection against breakthrough infection, especially with variants of concern. Adapted vaccination regimens may be needed to provide optimal protection against COVID-19 to vulnerable populations.