key: cord-0757565-jw19p6qj authors: Breznik, Jessica A.; Zhang, Ali; Huynh, Angela; Miller, Matthew S.; Nazy, Ishac; Bowdish, Dawn M.E.; Costa, Andrew P. title: Antibody Responses 3-5 Months Post-Vaccination with mRNA-1273 or BNT163b2 in Nursing Home Residents date: 2021-11-01 journal: J Am Med Dir Assoc DOI: 10.1016/j.jamda.2021.10.001 sha: 3a79ce25b2cbe17cc51322354547392b830e271e doc_id: 757565 cord_uid: jw19p6qj nan Antibody Responses 3-5 Months Post-Vaccination with mRNA-1273 or BNT163b2 in Nursing Home Residents Q 1 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 Nursing home 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. Residents were recruited from 8 sites nursing 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. 3 All protocols were approved by the Hamilton Integrated Research Ethics Board, and informed consent was obtained. Data are reported as a ratio of observed optical density to the determined assay cutoff optical density, 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% (MNT 50 ), which ranged from below detection (MNT 50 ¼ 10) to MNT 50 ¼ 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, National Institute of Allergy and Infectious Diseases, National Institutes of Health: SARS-Related Coronavirus 2, Isolate hCoV-19/ South Africa/KRISP-K005325/2020, NR-54009, contributed by Alex Sigal and Tulio de Oliveira. 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 t test (mean). All statistical analyses were conducted using SAS, version 9.4 (SAS Institute Inc, Cary, NC). The majority of residents (97.1%) produced antibodies to the spike (S) protein post vaccination; however, fewer residents (87.68%) produced immunoglobulin G (IgG) to the receptorbinding domain (RBD) domain (Table 1) . Residents who received mRNA-1273 had higher median levels of IgG S protein [mRNA-1273 ¼ 2.9, interquartile range (IQR) 2.5-3.1] and IgG RBD (mRNA-1273 ¼ 2.5, IQR 1.7-3.0) than those who received BNT163b2 (IgG Spike: BNT163b2 ¼ 2.5, IQR 1.5-3.1, P ¼ .015; IgG RBD: BNT163b2 ¼ 1.5, IQR 0.7-2.6, P < .001). Participants who had been vaccinated with BNT163b2 had median values of both Ig Spike and RBD that were lower than the median values of a cohort of convalescent individuals. There were no differences between vaccine groups with respect to IgM/A to either S protein or RBD. No neutralizing antibodies were detected in w20% of residents to the wild-type virus (30/155; 19%) or beta variant (27/ 134; 20%). Residents that received BNT163b2 had an w4-fold reduction in neutralization to the wild-type strain and a w2fold reduction in neutralization to the beta variant relative to those who received mRNA-1273. Two doses of vaccine failed to elicit any antibody-mediated protective immunity in w20% 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 with healthy young individuals. 4e6 In addition, we found that vaccination against SARS-CoV-2 with mRNA-1273 elicited a stronger humoral response compared with BNT162b2, with greater circulating IgG and neutralization antibody titers w3 months after vaccination. The 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. 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 on behalf of the Congregate Care Setting Working Group and the Ontario COVID-19 Science Advisory Table. Early impact of Ontario's COVID-19 vaccine rollout on long-term care home residents and health care workers. Science table: COVID-19 Advisory for Ontario 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 We acknowledge administrative and technical assistance from Tara Kajaks, PhD, Ahmad Rahim, MSc, Komal Aryal, MSc, Megan Hagerman, Braeden Cowbrough, MSc, Lucas Bilaver, Sheneice Joseph, and Leslie Tan who were compensated for their contributions by a grant funded by the Canadian COVID-19 Immunity Task Force at McMaster University.