COVID-19 vaccine booster dose needed to achieve Omicron-specific neutralisation in nursing home residents

Abstract

Background: Nursing home (NH) residents have borne a disproportionate share of SARS-CoV-2 morbidity and mortality. Vaccines have limited hospitalisation and death from earlier variants in this vulnerable population. With the rise of Omicron and future variants, it is vital to sustain and broaden vaccine-induced protection. We examined the effect of boosting with BNT162b2 mRNA vaccine on humoral immunity and Omicron-specific neutralising activity among NH residents and healthcare workers (HCWs).

Methods: We longitudinally enrolled 85 NH residents (median age 77) and 48 HCWs (median age 51), and sampled them after the initial vaccination series; and just before and 2 weeks after booster vaccination. Anti-spike, anti-receptor binding domain (RBD) and neutralisation titres to the original Wuhan strain and neutralisation to the Omicron strain were obtained.

Findings: Booster vaccination significantly increased vaccine-specific anti-spike, anti-RBD, and neutralisation levels above the pre-booster levels in NH residents and HCWs, both in those with and without prior SARS-CoV-2 infection. Omicron-specific neutralisation activity was low after the initial 2 dose series with only 28% of NH residents' and 28% HCWs' titres above the assay's lower limit of detection. Omicron neutralising activity following the booster lifted 86% of NH residents and 93% of HCWs to the detectable range.

Interpretation: With boosting, the vast majority of HCWs and NH residents developed detectable Omicron-specific neutralising activity. These data provide immunologic evidence that strongly supports booster vaccination to broaden neutralising activity and counter waning immunity in the hope it will better protect this vulnerable, high-risk population against the Omicron variant.

Funding: NIH AI129709-03S1, U01 CA260539-01, CDC 200-2016-91773, and VA BX005507-01.

Keywords: Booster; COVID-19; Geriatrics; Long-term care; Omicron; Vaccination.

Figure 1

Neutralisation titres over time pre- and post-boost with BNT162b2 mRNA vaccination in HCW and NH residents, with and without prior SARS-CoV-2 infection. a. Wuhan (vaccine) strain, b. Omicron strain. Pseudovirus neutralisation (pNT50) values are shown. The upper limit of detection of the assay is 1:8748 and the lower limit of detection (LLD) of the neutralisation assay is 1:12. The centre 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 interquartile range (height of box) away from the first and third quartile values with ∗ indicating p<0.05 and ∗∗∗ indicating p< 0.001. 2 weeks (2W Post-vax) after primary vaccination series and Pre-boost (generally 8-9 months after the first two-dose vaccination series) and Post-boost which is 14±3 days after vaccine boost.

Figure 2

Anti-spike and Anti-Receptor binding domain (RBD) levels over time pre- and post-boost with BNT162b2 mRNA vaccination in healthcare workers (HCWs) and nursing home (NH) residents, with and without prior SARS-CoV-2 infection. a. Anti-spike values depicted in the binding arbitrary units/millilitre (BAU/ml) based on the WHO standard. The cutoff for a positive anti-spike response over pre-pandemic controls is 3.8 BAU/ml. b. Anti-RBD values depicted in the arbitrary units (AU) with ∗ indicating p<0.05 and ∗∗∗ indicating p<0.001. Both proteins are to Wuhan strain. 2 weeks (2W Post-vax) after primary vaccination series and Pre-boost (generally 8-9 months after the first two-dose vaccination series) and Post-boost which is 14±3 days after vaccine boost.

Figure 3

Subjects with detectable Omicron neutralisation titres. Indicates the percentage of subjects in each clinical group with detectable neutralisation titres above LLD for Wuhan (vaccine) vs Omicron strains.