A Third Dose of SARS-CoV-2 Vaccine Increases Neutralizing Antibodies Against Variants of Concern in Solid Organ Transplant Recipients

Karaba, Andrew H.; Zhu, Xianming; Liang, Tao; Wang, Kristy; Rittenhouse, Alex; Akinde, Olivia; Eby, Yolanda; Blankson, Joel N.; Teles, Aura T.; Alejo, Jennifer L; Cox, Andrea L.; Bailey, Justin R.; Klein, Sabra L.; Pekosz, Andrew; Garonzik-Wang, Jacqueline M; Boyarsky, Brian J.; Segev, Dorry L.; Tobian, Aaron A.R.; Werbel, William A

doi:10.1101/2021.08.11.21261914

Cited by 47 publications

(72 citation statements)

References 27 publications

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“…For measurement of functional antibodies, ACE2-inhibition assays are a strong surrogate of live virus neutralization [24,39]. In terms of responses to VOC, the reductions in anti-S IgG to the Alpha and Delta variants observed in the older adults were similar to other reports in the general population [40].…”

Section: Discussionsupporting

confidence: 65%

“…The inclusion of three measures of humoral immunity and four SARS-CoV-2 viruses allowed us to capture the breadth and depth of vaccine responses in this vulnerable population. For measurement of functional antibodies, ACE2-inhibition assays are a strong surrogate of live virus neutralization [24, 39]. In terms of responses to VOC, the reductions in anti-S IgG to the Alpha and Delta variants observed in the older adults were similar to other reports in the general population [40].…”

Section: Discussionmentioning

confidence: 59%

“…Results were expressed as the log10-transformed area under the curve (AUC) generated from ten three-fold serial plasma dilutions, as previously described [22]. The ability of plasma antibodies to inhibit ACE2 binding to S was measured using Meso Scale Diagnostics (MSD) V-PLEX SARS-CoV-2 ACE2 kits according to the manufacturer’s protocol at a dilution of 1:100 [24]. Data were expressed as the log10-transformed concentration (μg/ml) of ACE2-inhibiting antibodies (ACE2iAb), which are equivalent to anti-S monoclonal antibodies.…”

Section: Methodsmentioning

confidence: 99%

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Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

Shapiro

Park

Aytenfisu

et al. 2022

Preprint

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Background: Male sex and old age are risk factors for severe COVID-19, but the intersection of sex and aging on antibody responses to SARS-CoV-2 vaccines has not been characterized. Methods: Plasma samples were collected from older adults (75-98 years) before and after three doses of SARS-CoV-2 mRNA vaccination, and from younger adults (18-74 years) post-dose two, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S-receptor binding domain [S-RBD], and nucleocapsid [N]) and functional activity against S were measured against the vaccine virus and variants of concern (VOC). Results: Vaccination induced greater antibody titers in older females than males, with both age and frailty associated with reduced antibody responses to vaccine antigens in males, but not females. ACE2 binding inhibition declined more than anti-S or anti-S-RBD IgG in the six months following the second dose (28-fold vs. 12- and 11-fold decreases in titer). The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOC were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOC than females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with disparities being greater in males than females. Conclusion: Older and frail males may be more vulnerable to breakthrough infections due to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 59%

Section: Methodsmentioning

confidence: 99%

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Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

Shapiro

Park

Aytenfisu

et al. 2022

Preprint

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“…15 There is increasing evidence on the efficacy of a third dose of vaccine in enhancing protective effect. [16][17][18][19] However, data on CoronaVac are limited. A study in healthy adults demonstrated a strong humoral booster following an additional dose administered 8 months after the primary schedule, indicating an efficient recalling of SARS-CoV-2-specific immune memory.…”

Section: Introductionmentioning

confidence: 99%

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases

et al. 2022

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ObjectiveTo determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response.MethodsAdult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination.ResultsARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001).ConclusionsWe provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX.Trial registration numberNCT04754698.

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“…Due to the decline in antibody titers over time after vaccination, booster shots have been recommended for all adults 9,10 . Boosters are thought to be especially important for immunosuppressed patients due to their impaired response to primary vaccination [11][12][13] . Here, we compare the humoral and cellular immune responses to SARS-CoV-2 after primary and booster vaccination among immunosuppressed patients.…”

Section: Introductionmentioning

confidence: 99%

Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients

Yang

Costales

Ramanathan

et al. 2022

Preprint

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Importance: Data on the humoral and cellular immune response to primary and booster SARS-CoV-2 vaccination in immunosuppressed patients is limited. Objective: To determine humoral and cellular response to primary and booster vaccination in immunosuppressed patients and identify variables associated with poor response. Design: Retrospective observational cohort study. Setting: Large healthcare system in Northern California. Participants: This study included patients fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) who underwent clinical testing for anti-SARS-SoV-2 S1 IgG ELISA (anti-S1 IgG) and SARS-CoV-2 interferon gamma release assay (IGRA) from January 1, 2021 through November 15, 2021. A cohort of 18 immunocompetent volunteer healthcare workers were included as reference. No participants had a prior diagnosis of SARS-CoV-2 infection. Exposure(s): Immunosuppressive diseases and therapies. Main Outcome(s) and Measure(s): Humoral and cellular SARS-CoV-2 vaccine response as measured by anti-S1 IgG and SARS-CoV-2 IGRA, respectively, after primary and booster vaccination. Results: 496 patients (54% female; median age 50 years) were included in this study. Among immunosuppressed patients after primary vaccination, 62% (261/419) had positive anti-S1 IgG and 71% (277/389) had positive IGRA. After booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Immunosuppressive factors associated with low rates of humoral response after primary vaccination included anti-CD20 monoclonal antibodies (n=48, P<.001), sphingosine 1-phsophate (S1P) receptor modulators (n=11, P<.001), mycophenolate (n=78, P=.002), and B cell lymphoma (n=55, P=.004); those associated with low rates of cellular response included S1P receptor modulators (n=11, P<.001) and mycophenolate (n=69, P<.001). Of patients who responded poorly to primary vaccination, 16% (4/25) with hematologic malignancy or primary immunodeficiency developed a significantly increased humoral response after the booster dose, while 52% (14/27) with solid malignancy, solid organ transplantation, or autoimmune disease developed an increased response (P=.009). Only 5% (2/42) of immunosuppressed patients developed a significantly increased cellular response following the booster dose. Conclusions and Relevance: Cellular vaccine response rates were higher than humoral response rates in immunosuppressed individuals after primary vaccination, particularly among those undergoing B cell targeting therapies. However, humoral response can be increased with booster vaccination, even in patients on B cell targeting therapies.

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A Third Dose of SARS-CoV-2 Vaccine Increases Neutralizing Antibodies Against Variants of Concern in Solid Organ Transplant Recipients

Cited by 47 publications

References 27 publications

Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

Association of frailty, age, and biological sex with SARS-CoV-2 mRNA vaccine-induced immunity in older adults

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases

Cell-mediated and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients

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