SARS-CoV-2 Antibody Responses to the Ancestral SARS-CoV-2 Strain and Omicron BA.1 and BA.4/BA.5 Variants in Nursing Home Residents After Receipt of Bivalent COVID-19 Vaccine - Ohio and Rhode Island, September-November 2022

Abstract

Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the period of Omicron variant predominance led to recommendations for booster doses with bivalent COVID-19 mRNA vaccines that include an Omicron BA.4/BA.5 spike protein component to broaden immune response and improve vaccine effectiveness against circulating Omicron variants (2). Recent studies suggest that bivalent booster doses provide substantial additional protection against SARS-CoV-2 infection and severe COVID-19-associated disease among immunocompetent adults who previously received only monovalent vaccines (3).* The immunologic response after receipt of bivalent boosters among nursing home residents, who often mount poor immunologic responses to vaccines, remains unknown. Serial testing of anti-spike protein antibody binding and neutralizing antibody titers in serum collected from 233 long-stay nursing home residents from the time of their primary vaccination series and including any subsequent booster doses, including the bivalent vaccine, was performed. The bivalent COVID-19 mRNA vaccine substantially increased anti-spike and neutralizing antibody titers against Omicron sublineages, including BA.1 and BA.4/BA.5, irrespective of previous SARS-CoV-2 infection or previous receipt of 1 or 2 booster doses. These data, in combination with evidence of low uptake of bivalent booster vaccination among residents and staff members in nursing homes (4), support the recommendation that nursing home residents and staff members receive a bivalent COVID-19 booster dose to reduce associated morbidity and mortality (2).

FIGURE 1

Pseudovirus neutralization assay results for Wuhan (top panels), Omicron BA.1 (middle panels), and Omicron BA.4/BA.5 strains (bottom panels) in nursing home residents after receipt of 1 (left panels) or 2 (right panels) previous monovalent booster doses and before and after receiving a COVID-19 bivalent booster dose — Ohio and Rhode Island, September–November 2022 Abbreviations: LLD = lower limit of detection; pNT50 = pseudovirus neutralization. * The upper limit of detection of the assay is 1:8,748, and the LLD of the neutralization assay is 1:12. The center line indicates the median, and the bottom and top of the boxes indicate the first and third quartiles, respectively. The lower and upper vertical lines extend from the first and third quartile lines, respectively, to the smallest and largest values no more than 1.5 times the IQR (height of box) away from the first and third quartile values. Values beyond that appear as points. ^† Testing after receipt of booster doses occurred a median of 17 days after vaccination in all groups. In the group that received 1 monovalent booster dose, testing before bivalent dose occurred 11 months after receipt of the first booster dose and a median of 48 days before receipt of the bivalent booster dose. In the group that received 2 monovalent booster doses, testing before the bivalent dose occurred 3 months after receipt of the second booster dose and a median of 49 days before administration of the bivalent booster dose. ^§ Pseudovirus neutralization assay is the method used to measure the ability of antibodies in the serum to neutralize the capability of a virus to enter cells and prevent infection using a pseudovirus containing a nonpathogenic virus core surrounded by a lipid envelope containing the SARS-CoV-2 spike protein surface glycoproteins of the virus strains of interest.

FIGURE 2

Anti-spike antibody assay results for Wuhan (top panels), Omicron BA.1 (middle panels), and Omicron BA.4/BA.5 strains (bottom panels) in nursing home residents after receipt of 1 (left panels) or 2 (right panels) previous monovalent booster doses and before and after receiving a COVID-19 bivalent booster dose — Ohio and Rhode Island, September–November 2022 Abbreviations: AU = arbitrary units; BAU = binding antibody units. * Anti-spike levels for BA.1 and BA.4/BA.5 are in arbitrary units (AU/mL) with an internal standard allowing comparison across timepoints in this dataset. Wuhan-anti-spike is in binding antibody units (BAU/mL) that are based on the World Health Organization 20/136 standard. The center line indicates the median, and the bottom and top of the box indicate the first and third quartile, respectively. The lower and upper whiskers extend from the first and third quartile lines, respectively, to the smallest and largest values no more than 1.5 times the IQR (height of box) away from the first and third quartile values. Values beyond that appear as points. ^† Testing after receipt of booster doses occurred a median of 17 days after vaccination in all groups. In the group that received 1 monovalent booster dose, testing before bivalent dose occurred 11 months after receipt of the first booster dose and a median of 48 days before receipt of the bivalent booster dose. In the group that received 2 monovalent booster doses, testing before the bivalent dose occurred 3 months after receipt of the second booster dose and a median of 49 days before administration of the bivalent booster dose.