Neutralizing antibody responses to SARS-CoV-2 variants in vaccinated Ontario long-term care home residents and workers

Abe, K. T.; Hu, Q.; Mozafarihashjin, M.; Samson, R.; Manguiat, K.; Robinson, A.; Rathod, B.; Chao, G.; Wang, J. H.; Iskilova, M.; Pasculescu, A.; Fazel-Zarandi, M.; Li, A.; Paterson, A.; Green, K.; Gilbert, L.; Barati, S.; Haq, N.; Takaoka, A.; Garnham Takaoka, J.; Quinn De Launay, K.; Fahim, C.; Sheikh-Mohamed, S.; Arita, Y.; Durocher, Y.; Marcusson, E. G.; Gommerman, J. L.; Ostrowski, M.; Colwill, K.; Straus, S. E.; Wood, H.; McGeer, A. J.; Gingras, A.-C.

Prioritizing Ontario's long-term care home (LTCH) residents for vaccination against severe acute respiratory syndrome coronavirus 2 has drastically reduced their disease burden; however, recent LTCH outbreaks of variants of concern (VOCs) have raised questions regarding their immune responses. In 199 residents, mRNA vaccine dose 1 elicited partial spike and receptor binding domain antibody responses, while the second elicited a response at least equivalent to convalescent individuals in most residents. Residents administered mRNA-1273 (Moderna) mounted stronger total and neutralizing antibody responses than those administered BNT162b2 (Pfizer-BioNTech). Two to four weeks after dose 2, residents (n = 119, median age 88) produced 4.92-6.5-fold fewer neutralizing antibodies than staff (n = 78; median age 45) against wild-type (with D614G) pseudotyped lentivirus, and residents administered BNT162b2 produced 2.95-fold fewer neutralizing antibodies than those who received mRNA-1273. These effects were exacerbated upon serum challenge with pseudotyped VOC spike, with up to 6.64-fold reductions in B.1.351 (Beta) neutralization. Cumulatively, weaker vaccine stimulation, age/comorbidities, and the VOC produced an ~130-fold reduction in apparent neutralization titers in LTCH residents and 37.9% of BNT162b2-vaccinated residents had undetectable neutralizing antibodies to B.1.351. Continued immune response surveillance and additional vaccine doses may be required in this population with known vulnerabilities.