key: cord-0966157-gm4c9z1x authors: Breznik, J. A.; Zhang, A.; Huynh, A.; Miller, M. S.; Nazy, I.; Bowdish, D. M. E.; Costa, A. P.; Group, COVID-in-LTC Study title: Antibody Responses 3-5 Months Post-Vaccination with mRNA-1273 or BNT163b2 in Nursing Home Residents date: 2021-08-18 journal: nan DOI: 10.1101/2021.08.17.21262152 sha: 0e81f57c0d2fee7204416c2f482a553d67a045f2 doc_id: 966157 cord_uid: gm4c9z1x Nursing homes residents often fail to mount robust responses to vaccinations and recent reports of breakthrough infections, particularly from variants of concern, raise questions about whether vaccination regimens elicit a sufficient humoral immune response or if booster doses are warranted. We examined SARS-CoV-2 antibody levels and neutralizing capacity in nursing home residents 3-5 months after 2 doses of mRNA-1273 or BNT163b2 vaccination as per recommended schedules. Nursing home residents were recruited from eight long-term care homes in Ontario, Canada, between March and July 2021. Antibody levels and neutralization capacity from a previously published convalescent cohort were used as a comparator.Serum SARS-CoV-2 IgA/G/M against spike (S) protein and its receptor-binding domain (RBD) were measured by validated ELISA, with assay cut-off at the mean and 3 standard deviations of a pre-COVID-19 population from the same geographic region. Antibody neutralization was measured against the wild-type strain of SARS-CoV-2 and the beta variant of concern (B.1.351). No neutralizing antibodies were detected in ~20% of residents to the wild-type virus (30/155; 19%) or beta variant (27/134; 20%). Residents that received BNT163b2 had a ~4-fold reduction in neutralization to the wild-type strain, and a ~2-fold reduction in neutralization to the beta variant relative to those who received mRNA-1273. Current mRNA SARS-CoV-2 vaccine regimens may not have equivalent efficacy in nursing home residents. Our findings imply that differences in the humoral immune response may contribute to breakthrough infections, and suggest that consideration of the type of vaccine administered to older adults will have a positive impact on the generation of protective immunity. No neutralizing antibodies were detected in ~20% of residents to the wild-type virus (30/155; 19%) or beta variant (27/134; 20%). Residents that received BNT163b2 had a ~4-fold reduction in neutralization to the wild-type strain, and a ~2-fold reduction in neutralization to the beta variant relative to those who received mRNA-1273. Current mRNA SARS-CoV-2 vaccine regimens may not have equivalent efficacy in nursing home residents. Our findings imply that differences in the humoral immune response may contribute to breakthrough infections, and suggest that consideration of the type of vaccine administered to older adults will have a positive impact on the generation of protective immunity. Nursing home residents in Ontario, Canada, were prioritized for vaccination with mRNA vaccines from Moderna (mRNA-1273) or Pfizer (BNT163b2) in December 2020-January 2021, which significantly reduced the high morbidity and mortality due to COVID-19 1 . Yet nursing homes residents often fail to mount robust responses to vaccinations 2 and recent reports of breakthrough infections, particularly from variants of concern, raise questions about whether vaccination regimens elicit a sufficient humoral immune response or if booster doses are warranted. We examined SARS-CoV-2 antibody levels and neutralizing capacity in nursing home residents 3-5 months after 2 doses of mRNA-1273 or BNT163b2 vaccination as per recommended schedules. Nursing home residents were recruited from eight long-term care homes in Ontario, Canada, between March and July 2021. Antibody levels and neutralization capacity from a previously published convalescent cohort were used as a comparator 2 . All protocols were approved by the Hamilton Integrated Research Ethics Board, and informed consent was obtained. Venous blood was drawn in anti-coagulant-free vacutainers for isolation of serum. Serum SARS-CoV-2 IgA/G/M against spike (S) protein and its receptor-binding domain (RBD) were measured by validated ELISA, with assay cut-off at the mean and 3 standard deviations of a pre-COVID-19 population from the same geographic region 3 . Data are reported as a ratio of observed optical density (OD) to the determined assay cut-off OD, with ratios above 1 considered positive. Neutralization capacity of these antibodies was assessed by cell culture assays with live SARS-CoV-2 virus, with data reported as geometric microneutralization titers at 50% (MNT50) which ranged from below detection (MNT50 = 10) to MNT50 = 1280 3 . Antibody neutralization was measured against the wild-type strain of SARS-CoV-2 and the beta variant of concern (B.1.351). The beta variant was obtained through BEI Resources, NIAID, NIH: SARS-Related Coronavirus 2, . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 18, 2021. Differences between antibody levels and neutralization in individuals that received mRNA-1273 or BNT163b2 were assessed by chi-square of independence (proportions), Kruskal-Wallis test (median), and student's t-test (mean). All statistical analyses were conducted using SAS 9.4 (SAS Institute Inc.). The majority of residents (97.1%) produced antibodies to the S protein post vaccination; however, fewer residents (87.68%) produced IgG to the RBD domain (Table) . Residents who Double vaccination failed to elicit any antibody-mediated protective immunity in ~20% of nursing home residents. These data align with recent observations of decreased antibody production and/or neutralization after BNT162b2 vaccination in nursing home residents compared to healthy young individuals 4-6 . In addition, we found that vaccination against SARS-CoV-2 with mRNA-1273 elicited a stronger humoral response compared to BNT162b2, with greater circulating IgG and neutralization antibody titers ~3 months after vaccination. The . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.17.21262152 doi: medRxiv preprint mRNA-1273 vaccine contains a higher dose of mRNA, which may imply that a higher dose is beneficial to generate protective immunity in nursing home residents. Current mRNA SARS-CoV-2 vaccine regimens may not have equivalent efficacy in nursing home residents. Our findings imply that differences in the humoral immune response may contribute to breakthrough infections, and suggest that consideration of the type of vaccine administered to older adults will have a positive impact on the generation of protective immunity. Blue bars indicate median values. Dotted lines represent the level of detection. Microneutralization titres (MNT) are visualized as a log scale and individuals who did not have any detectable neutralization capacity (SB3: n=1, mRNA-1273 and n=10 BNT163b) are not included. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.17.21262152 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.17.21262152 doi: medRxiv preprint Early impact of Ontario's COVID-19 vaccine rollout on long-term care home residents and health care workers Immunosenescence and vaccination in nursing home residents Characteristics of Anti-SARS-CoV-2 Antibodies in Recovered COVID-19 Subjects Reduced BNT162b2 mRNA vaccine response in SARS-CoV-2-naive nursing home residents. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Antibody Responses After mRNA Vaccination in Residential Older Adults: Implications for Reopening Vaccines Among Residents of Long-Term Care Facilities