Differential Anti-S Antibody Titers in Vaccinated Residents During an Outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant B.1.351 (β) in an Elderly Nursing Home

To the Editor— We previously reported an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.351 (β) in a nursing home where 83.9% of residents had been fully vaccinated by means of the BNT162b2 messenger RNA (mRNA) vaccine [1]. We read with interest the letter from Vanker and colleagues, who reported a similar outbreak of the same SARS-CoV-2 variant in a Canadian nursing home, despite a high vaccination rate among residents and staff members [2]. Both studies suggested that BNT162b2 mRNA vaccination does not fully protect from outbreaks of SARS-CoV-2 variant B.1.351 (β) in elderly nursing homes. We further investigated the anti-SARS-CoV-2 immune response in our vaccinated cohort, comparing anti-SARS CoV-2 antibody levels in noninfected versus infected residents. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies targeting the spike receptor-binding domain (RBD) antigen were sought by means of the Abbott IgG anti-S kit (Abbott Diagnostics, Lake Forest, Illinois, USA). All vaccinated residents were tested for anti-S antibodies within 1 to 2 months and a half after the second dose of vaccine. Those who were infected were tested within 9 days after the outbreak started (ie, within 4 days after symptom onset in symptomatic residents). Overall, the levels of anti-S antibodies did not differ between those who were infected (n = 13) and those who were not (n = 13): median 1069 AU/mL (range < 6.8–8188 AU/mL) vs median 1481 AU/mL (range 448–2928 AU/mL), respectively (P = .76: Figure 1). The anti-S antibody levels did not significantly differ between vaccinated patients with a severe vs nonsevere infection. However, the 2 infected vaccinated residents who died from the infection had relatively low antibody levels 1 month after the second vaccine dose (139 and 643 AU/mL, respectively). Levels of anti-S (RBD) antibodies among 13 vaccinated, B.1.351 (β) infected residents, versus 13 vaccinated not-infected residents. Abbreviation: RBD, receptor-binding domain. A high level of anti-S antibodies (>1000 AU/mL) has been associated with in vitro viral neutralization of all major circulating variants of concern, including variant B.1.1.7 (α) [3]. In the majority of elderly patients, antibody responses elicited by 2 doses of the BNT162b2 mRNA vaccine are sufficient to protect against infection or, if infected, severe disease related to the initial SARS-CoV-2 strains or variant B.1.1.7 (α). However, these responses may be insufficient to induce high-level protection against severe disease in some individuals infected with variant B.1.351 (β), a variant carrying several mutations suggested to reduce susceptibility to antibody neutralization (eg, S-Del242-244, S-K417N, S-E484K). Recently, Kamar et al showed that a third dose of the BNT162b2 mRNA vaccine significantly improved the immunogenicity of vaccination in solid organ transplant recipients [4]. The effectiveness of a third vaccine dose, as reflected by anti-S antibody levels, should be explored in elderly individuals, as it may enhance their immune response and ensure protection against emerging variants with reduced susceptibility to neutralizing antibodies. Larger observational studies are needed to confirm this hypothesis. Note Potential conflict of interest. S. F. has served as a paid speaker for Abbvie and Abbott diagnostics and has served on an advisory board/Data and Safety Monitoring Board (DSMB) for Merck (MSD), outside the submitted work. C. R. has served as an advisor, and/or speaker for Illumina, and Vela Diagnostics. J.-M. P. has served as a paid advisor, and/or speaker for Abbvie, Gilead, GlaxoSmithKline, Merck, Regulus, and Siemens Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.