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

Abstract

Background: Vaccines have substantially mitigated the disproportional impact of SARS-CoV-2 on the high morbidity and mortality experienced by nursing home residents. However, variation in vaccine efficacy, immune senescence and waning immunity all undermine vaccine effectiveness over time. The introduction of the bivalent vaccine in September 2022 aimed to counter this increasing susceptibility and consequences of breakthrough infection, however data on the durability and protection of the vaccine are limited. We evaluated the durability of immunity and protection after the first bivalent vaccination to SARS-CoV-2 in nursing home residents. Methods: For the immunologic evaluation, community nursing home volunteers agreed to serial blood sampling before, at two weeks, three and six months after each vaccination for antibodies to spike protein and pseudovirus neutralization activity over time. Concurrent clinical outcomes were evaluated by reviewing electronic health record data from residents living in Veterans Administration managed nursing home units. Residents without recent infection but prior vaccination to SARS-CoV-2 were followed over time beginning with administration of the newly available bivalent vaccine using a target trial emulation (TTE) approach; TTE compared time to breakthrough infection, hospitalization and death between those who did and did not receive the bivalent vaccine. Results: We evaluated antibodies in 650 nursing home residents; 452 had data available following a first monovalent booster, 257 following a second monovalent booster and 321 following a bivalent vaccine. We found a rise in BA.5 neutralization activity from the first and second monovalent boosters through the bivalent vaccination regardless of prior SARS-CoV-2 history. Titers declined at three and six months after the bivalent vaccination but generally exceeded those at three months compared to either prior boost. BA.5 neutralization titers six months after the bivalent vaccination were diminished but had detectable levels in 80% of infection-naive and 100% of prior infected individuals. TTE evaluated 5903 unique subjects, of whom 2235 received the bivalent boost. TTE demonstrated 39% or greater reduction in risk of infection, hospitalization or death at four months following the bivalent boost. Conclusion: Immunologic results mirrored those of the TTE and suggest bivalent vaccination added substantial protection for up to six months after bivalent vaccination with notable exceptions. However, the level of protection declined over this period, and by six months may open a window of added vulnerability to infection before the next updated vaccine becomes available. We strongly agree with the CDC recommendation that those who have not received a bivalent vaccination receive that now and these results support a second bivalent booster for those at greatest risk which includes many nursing home residents.

Poor durability of the neutralizing response against XBB sublineages after a bivalent mRNA COVID‐19 booster dose in persons with HIV

“…We confirmed the role of hybrid immunity, defined as the history of SARS‐CoV‐2 natural infection in vaccinated people, in achieving higher levels of nAbs against all the tested variants. Indeed, in line with previous reports, nAbs titers were constantly higher in HI than in nHI at each time point and against all the variants tested 23–26 …”

Neutralization and binding antibody response to second bivalent COVID‐19 vaccination in nursing home residents

“…The current analysis extends our longitudinal data evaluating serial blood draws from consented NH residents vaccinated with the COVID‐19 mRNA vaccines 2–5 . We summarize findings from 2 weeks after each of four vaccination time points (first and second monovalent boosters, first and second bivalent boosters) and an intermediate draw 3–6 months after the first bivalent booster.…”

“…Vaccination plays a vital role in preventing SARS‐CoV‐2 infection and reducing morbidity and mortality burden in this population. A single bivalent COVID‐19 mRNA vaccine broadens SARS‐CoV‐2 immunity and reduces infection, hospitalization, and death beyond that from monovalent vaccination 2,3 . We extend our work here by evaluating the immune response following a second bivalent vaccine dose.…”

“…A single bivalent COVID-19 mRNA vaccine broadens SARS-CoV-2 immunity and reduces infection, hospitalization, and death beyond that from monovalent vaccination. 2,3 We extend our work here by evaluating the immune response following a second bivalent vaccine dose.…”

“…The current analysis extends our longitudinal data evaluating serial blood draws from consented NH residents vaccinated with the COVID-19 mRNA vaccines. [2][3][4][5] We summarize findings from 2 weeks after each of four vaccination time points (first and second monovalent boosters, first and second bivalent boosters) and an intermediate draw 3-6 months after the first bivalent booster. We exclude data points from subjects with an interval infection (positive polymerase chain reaction or antigen test) and/or laboratory criteria [positive nucleocapsid (N) protein or a rise outside of lab variance of anti-spike (S), N, or neutralizing assay results not accounted for by vaccination history] until their next vaccine dose.…”