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. 2024 Jul:105:105180.
doi: 10.1016/j.ebiom.2024.105180. Epub 2024 Jun 10.

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination

Stefan Gravenstein  1 , Frank DeVone  2 , Oladayo A Oyebanji  3 , Yasin Abul  4 , Yi Cao  5 , Philip A Chan  6 , Christopher W Halladay  2 , James L Rudolph  7 , Clare Nugent  8 , Jürgen Bosch  3 , Christopher L King  3 , Brigid M Wilson  9 , Alejandro B Balazs  5 , Elizabeth M White  10 , David H Canaday  11 , Kevin W McConeghy  12
Affiliations

Durability of immunity and clinical protection in nursing home residents following bivalent SARS-CoV-2 vaccination

Stefan Gravenstein et al. EBioMedicine. 2024 Jul.

Abstract

Background: Bivalent SARS-CoV-2 vaccines were developed to counter increasing susceptibility to emerging SARS-CoV-2 variants. We evaluated the durability of immunity and protection following first bivalent vaccination among nursing home residents.

Methods: We evaluated anti-spike and neutralization titers from blood in 653 community nursing home residents before and after each monovalent booster, and a bivalent vaccine. Concurrent clinical outcomes were evaluated using electronic health record data from a separate cohort of 3783 residents of Veterans Affairs (VA) nursing homes who had received at least the primary series monovalent vaccination. Using target trial emulation, we compared VA residents who did and did not receive the bivalent vaccine to measure vaccine effectiveness against infection, hospitalization, and death.

Findings: In the community cohort, Omicron BA.5 neutralization activity rose after each monovalent and bivalent booster vaccination regardless of prior infection history. Titers declined over time but six months post-bivalent vaccination, BA.5 neutralization persisted at detectable levels in 75% of infection-naive and 98% of prior-infected individuals. In the VA nursing home cohort, bivalent vaccine added effectiveness to monovalent booster vaccination by 18.5% for infection (95% confidence interval (CI) -5.6, 34.0%), and 29.2% for hospitalization or death (95% CI -14.2, 56.2%) over five months.

Interpretation: The level of protection declined after bivalent vaccination over a 6 month period and may open a window of added vulnerability before the next updated vaccine becomes available, suggesting a subset of nursing home residents may benefit from an additional vaccination booster.

Funding: CDC, NIH, VHA.

Keywords: Antibodies; COVID-19; Effectiveness; Long-term care; Vaccine.

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Conflict of interest statement

Declaration of interests Stefan Gravenstein (S. G.) and David H. Canaday (D. H. C.) are recipients of investigator-initiated grants to their universities from Pfizer to study pneumococcal vaccines, Moderna to study respiratory infections, and Sanofi Pasteur and Seqirus to study influenza vaccines, and S.G. from Genentech on influenza antivirals. S. G. also receives consulting fees from GlaxoSmithKline, Icosavax, Janssen, Merck, Moderna, Novavax, Pfizer, Reviral, Sanofi, Seqirus, and Vaxart, and has received fees for speaking for Janssen, Pfizer, Moderna, GlaxoSmithKline, Sanofi, and Seqirus. KWM Investigator initiated research support from Seqirus pharmaceuticals, Sanofi-Pasteur, Genentech and Pfizer.

Figures

Fig. 1
Fig. 1
Pseudovirus neutralization results pre- and post-vaccination with COVID-19 booster vaccinations in a convenience sample of nursing home residents. The blue panels are COVID-19 infection-naive residents and the red panels include those prior history of COVID-19 infection. N refers to the number of samples for that group, not all subjects had available data for all timepoints. The boxplot represents the median (solid line), 25 and 75% quantiles (box) and 95% quantiles (tails). pNT50 = inverse of titre concentration where 50% pseudovirus neutralization. The limits of detection for the assay are 1:12 to 1:8748. See Figure S1 for further description of sampling timepoints and x-axis labels.
Fig. 2
Fig. 2
Decline of COVID-19 pseudovirus neutralization titers after vaccination with COVID-19 boosters. pNT50 neutralization titers of BA.5 (top) and Wuhan (bottom) plotted by days from a COVID-19 booster vaccination. COVID-19 infection naive (blue) and prior history of infection (red) are graphed separately. The lines represent conditional means of the log-transformed neutralization response adjusted for days since last vaccination and random intercepts for each included subject. Shaded regions represent the 95% confidence interval of the linear model prediction fixed effects.
Fig. 3
Fig. 3
Anti-spike titer results pre- and post- COVID-19 booster vaccination in a convenience sample of nursing home residents. This figure illustrates anti-spike for BA.5 (top) in AU/ml and Wuhan (bottom) in BAU/ml in nursing home residents before and after COVID-19 booster vaccinations. COVID-19 infection naive (blue) and prior history of infection (red) are graphed separately. N refers to the number of samples for that group, not all subjects had available data for all timepoints. The boxplot represents the median (solid line), 25 and 75% quantiles (box) and 95% quantiles (tails). See Figure S1 for further description of sampling timepoints and x-axis labels.
Fig. 4
Fig. 4
Differences in cumulative incidence by bivalent vaccination for SARS-CoV-2 clinical outcomes up to 26 weeks. Each solid blue line represents the difference in cumulative incidences by vaccination status with a corresponding 95% confidence interval (light blue shading) across weeks of follow-up. A vertical dashed line at 0 for reference.
See this image and copyright information in PMC

Update of

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Supplementary concepts