Durability of Bivalent Boosters against Omicron Subvariants

Lin, Danyu; Xu, Yangjianchen; Gu, Yu; Zeng, Donglin; Sunny, Shadia Khan; Moore, Zack

doi:10.1056/nejmc2302462

Cited by 79 publications

(53 citation statements)

References 3 publications

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“…In this study, we show that the durability of NAb responses to WA1/2020 is relatively robust but that the magnitude and durability of NAb responses to XBB subvariants are more limited following bivalent mRNA boosting. This finding is consistent with recent clinical efficacy studies that have reported that the bivalent mRNA vaccines provided minimal protection against acquisition of infections that waned from 29% to 0% after 20 weeks and moderate protection against severe disease that waned from 67% to 38% after 20 weeks (33), during a time when XBB variants were predominant.…”

Section: Discussionsupporting

confidence: 91%

Waning immunity and IgG4 responses following bivalent mRNA boosting

Lasrado,

Collier,

Miller

et al. 2024

Sci. Adv.

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Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but the efficacy of bivalent mRNA boosters against XBB variants was substantially lower. Here, we show limited durability of neutralizing antibody (NAb) responses against XBB variants and isotype switching to immunoglobulin G4 (IgG4) responses following bivalent mRNA boosting. Bivalent mRNA boosting elicited modest XBB.1-, XBB.1.5-, and XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, bivalent mRNA boosting induced more robust and sustained NAbs against the ancestral WA1/2020 strain, suggesting immune imprinting. Following bivalent mRNA boosting, serum antibody responses were primarily IgG2 and IgG4 responses with poor Fc functional activity. In contrast, a third monovalent mRNA immunization boosted all isotypes including IgG1 and IgG3 with robust Fc functional activity. These data show substantial immune imprinting for the ancestral spike and isotype switching to IgG4 responses following bivalent mRNA boosting, with important implications for future booster designs and boosting strategies.

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Section: Discussionsupporting

confidence: 91%

Waning immunity and IgG4 responses following bivalent mRNA boosting

Lasrado,

Collier,

Miller

et al. 2024

Sci. Adv.

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“…Nevertheless, the proportion of samples still able to generate IFNγ in response to an in vitro SARS‐CoV‐2 stimulation remained high. This observation is consistent with the maintained and superior effectiveness against severe disease in the report of Lin et al 12 The fact that the release of IFNγ could represent a good surrogate of the risk of severe infection still remains to be evaluated. Importantly, these data can also help competent national authorities in their recommendation regarding the administration of an additional booster.…”

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 58%

“…This decrease was especially important considering the XBB.1.5 subvariant. Moreover, the drop of neutralizing antibodies over time coincides with the decrease of bivalent booster effectiveness against infection in the recent report of Lin et al 12 Compared to the ancestral strain, the omicron variant is characterized by the presence of around 32 mutations in the spike protein. 13 The spike protein of BA.5 is identical to BA.2 except for 69-70 deletion, L452R, F486V and the wild-type amino acid at Q493.…”

Section: Discussionmentioning

confidence: 82%

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Durability of humoral and cellular immunity six months after the BNT162b2 bivalent booster

Favresse,

Gillot,

Closset

et al. 2024

Journal of Medical Virology

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Studies about the duration of the humoral and cellular response following the bivalent booster administration are still scarce. We aimed at assessing the humoral and cellular response in a cohort of healthcare workers that received this booster. Blood samples were collected before the administration of the bivalent booster from Pfizer‐BioNTech and after 14, 28, 90, and 180 days. Neutralizing antibodies against either the D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5 subvariant were measured. The cellular response was assessed by measurement of the release of interferon gamma from T cells in response to an in vitro SARS‐CoV‐2 stimulation. A substantial waning of neutralizing antibodies was observed after 6 months (23.1‐fold decrease), especially considering the XBB.1.5 subvariant. The estimated T1/2 of neutralizing antibodies was 16.1 days (95% CI = 10.2–38.4 days). Although most participants still present a robust cellular response after 6 months (i.e., 95%), a significant decrease was also observed compared to the peak response (0.95 vs. 0.41 UI/L, p = 0.0083). A significant waning of the humoral and cellular response was observed after 6 months. These data can also help competent national authorities in their recommendation regarding the administration of an additional booster.

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“…Several other studies have initial effectiveness data after the bivalent vaccination. Lin et al published in the general population (17) and Arbel et al in persons over age 65 (18) and both found significant benefit from BV vaccinations. Arbel et al's study population was data from one of Israel's large public health services and not focused on long term care residents.…”

Section: Discussionmentioning

confidence: 95%

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

Gravenstein

DeVone

Oyebanji

et al. 2023

Preprint

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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.

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Durability of Bivalent Boosters against Omicron Subvariants

Cited by 79 publications

References 3 publications

Waning immunity and IgG4 responses following bivalent mRNA boosting

Waning immunity and IgG4 responses following bivalent mRNA boosting

Durability of humoral and cellular immunity six months after the BNT162b2 bivalent booster

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

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