scholarly journals Humoral immune responses against SARS-CoV-2 variants including omicron in solid organ transplant recipients after three doses of a COVID-19 mRNA vaccine

2022 ◽  
Author(s):  
Kapil K. Saharia ◽  
Jennifer S. Husson ◽  
Silke V. Niederhaus ◽  
Thierry Iraguha ◽  
Stephanie V. Avila ◽  
...  
Keyword(s):  
Immune Responses ◽  
Organ Transplant ◽  
Vaccine Dose ◽  
Solid Organ ◽  
Additional Dose ◽  
Transplant Recipients ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Antibody Titers ◽  
Solid Organ Transplant Recipients

BACKGROUND: Solid organ transplant recipients (SOTR), who typically receive post-transplant immunosuppression, show increased COVID-19-related mortality. It is unclear whether an additional dose of COVID-19 vaccines in SOTR can overcome the reduced immune responsiveness against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants. METHODS: We performed a prospective cohort study of 53 SOTR receiving SARS-CoV-2 vaccination into a prospective cohort study performing detailed immunoprofiling of humoral immune responses against SARS-CoV-2 and its variants. RESULTS: Prior to the additional vaccine dose, 60.3% of SOTR showed no measurable neutralization and only 18.9% demonstrated neutralizing activity of >90% following two vaccine doses. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titers against microbial recall antigens were in fact higher. In contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titers against SARS-CoV-2 and its delta variants. Vaccinated SOTR showed a markedly fewer linear B cell epitopes, indicating reduced B cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titers and neutralizing activity across alpha, beta and delta variants. However, we observed a significant decrease in anti-spike antibody titers with the omicron variant. CONCLUSIONS: Only a small subgroup of SOTR generated functionally relevant antibodies after completing the initial vaccine series based on dysfunctional priming of immune responses against novel antigens. An additional dose of the vaccine results in dramatically improved antibody responses against all SARS-CoV-2 variants except omicron.

scholarly journals 568. Comparison of Humoral Immune Response to the SARS-CoV-2 BNT162b2 Vaccine Between Solid Organ Transplant Recipients and Healthy Controls

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S386-S386
Author(s):  
Ahmad Yanis ◽  
Zaid Haddadin ◽  
Andrew Speaker ◽  
Danya Waqfi ◽  
Rana Talj ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Vaccine Dose ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Research Support ◽  
Material Support ◽  
Organ Transplant Recipients ◽  
Solid Organ Transplant Recipients

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased morbidity and mortality in immunocompromised individuals, including solid organ transplant recipients (SOTR). Despite being excluded from phase 1-3 SARS-CoV-2 vaccine clinical trials, SOTR were identified as high-risk populations and prioritized for vaccination in public health guidelines. We aimed to evaluate the antibody response to two doses of the BNT162b2 (Pfizer-BioNTech) vaccine in SOTR as compared to healthy controls (HC). Methods SOTR and HC scheduled to receive two doses of BNT162b2 vaccine and able to complete required follow-up visits were enrolled. Blood specimens were collected from participants before receiving the first and second doses and 21-42 days after the second dose. Enzyme-linked immunosorbent assay (ELISA) was used to detect immunoglobulin G (IgG) to the SARS-CoV-2 spike receptor-binding domain (RBD). Generalized estimating equations with a working independence correlation structure were used to compare anti-RBD IgG levels between SOTR and HC at each study visit and within each group over time. All models were adjusted for age, sex, and pre-vaccination seroreactivity in the ELISA. Results A total of 54 SOTR and 26 HC were enrolled, with mean (SD) ages of 72 (3.6) and 62 (6.7) years, 61% and 35% were male, and 91% and 88% were white, respectively. The most common organ transplant types were kidney (41%) and liver (37%). All SOTR were receiving calcineurin inhibitors. The median time post-transplantation was 7 years. SOTR had markedly lower mean anti-RBD IgG levels when compared to HC with adjusted mean differences of -0.76 (95%CI: [-1.04, -0.47]; p < 0.001) ELISA units (EU) and -1.35 (95%CI [-1.68, -1.01]; p < 0.001) EU after the first and second doses, respectively (Figure 1). Both groups had a significant increase in anti-SARS-CoV-2 IgG levels after the second dose. However, the magnitude was lower in SOTR, 0.49 (95%CI [0.31, 0.69]; p < 0.001) EU than in HCs, 1.08 (95% CI [0.91, 1.24]; p < 0.001) EU. Figure 1. Anti-SARS-CoV-2 RBD IgG levels in solid organ transplant recipients and healthy controls before receiving the BNT162b2 vaccine (baseline), post-vaccine dose 1, and post-vaccine dose 2. Conclusion Our study showed SOTR mounted weaker humoral immune responses than HC to SARS-CoV-2 vaccines. Given a lower response, SOTR should continue to practice social distancing and masking until data on vaccine efficacy are available in this vulnerable population. Disclosures Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it's a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it's a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support

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

2021 ◽  
Author(s):  
Andrew H Karaba ◽  
Xianming Zhu ◽  
Tao Liang ◽  
Kristy H Wang ◽  
Alex G Rittenhouse ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
Novel Variants ◽  
Antibody Titers ◽  
Solid Organ Transplant Recipients

Immunocompromised populations are at high risk for severe COVID-19. Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs), and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses may increase anti-spike antibody titers in some SOTRs, but whether this results in enhanced neutralizing capability, especially versus novel variants of concern (VOCs) that exhibit immune escape and higher infectivity (e.g., the Delta variant), is unclear. Here, we report that a third dose of a SARS-CoV-2 vaccine increases anti-SARS-CoV-2 spike and RBD IgG levels as well as plasma neutralizing capability versus VOCs, including Delta, in some SOTRs. However, anti-spike IgG and neutralizing capability remained significantly reduced compared to fully vaccinated healthy controls. These findings highlight the need for continued study of strategies to improve protection from COVID-19 in immunosuppressed populations as more SARS-CoV-2 VOCs emerge.

scholarly journals Efficacy and Safety of Third Dose of the COVID-19 Vaccine among Solid Organ Transplant Recipients: A Systemic Review and Meta-Analysis

Vaccines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 95
Author(s):  
Orly Efros ◽  
Roi Anteby ◽  
Mirit Halfon ◽  
Eshcar Meisel ◽  
Eyal Klang ◽  
...  
Keyword(s):  
Antibody Response ◽  
Organ Transplant ◽  
Vaccine Dose ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Efficacy And Safety ◽  
Transplant Recipients ◽  
Organ Transplant Recipients ◽  
The Third ◽  
Solid Organ Transplant Recipients

Solid organ transplant recipients were demonstrated to have reduced antibody response to the first and second doses of the COVID-19 mRNA vaccine. This review evaluated published data on the efficacy and safety of the third dose among solid organ transplant recipients. We performed a systematic search of PubMed, EMBASE, and Web of Science to retrieve studies evaluating the efficacy of the third dose of anti-SARS-CoV-2 vaccines in adult solid organ transplant recipients. Serologic response after the third vaccine was pooled using inverse variance and generalized linear mixed and random-effects models. Seven studies met our inclusion criteria. A total of 853 patients received the third dose. Except for one randomized controlled trial, all studies were retrospective in design. Following the third COVID-19 vaccine dose, antibody response occurred in 6.4–69.2% of patients. The pooled proportion of antibody response rate after the third vaccine was 50.3% (95% confidence interval (CI): 37.1–63.5, I2 = 90%). Five papers reported the safety profile. No severe adverse events were observed after the third vaccine dose. In conclusion, a third dose of the SARS-CoV-2 mRNA vaccine in solid organ transplant recipients is associated with improved immunogenicity and appears to be safe. Nevertheless, a significant portion of patients remain seronegative.

scholarly journals Long Term Immune Responses to Pandemic Influenza A/H1N1 Infection in Solid Organ Transplant Recipients

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e28627 ◽  
Author(s):  
Aliyah Baluch ◽  
Atul Humar ◽  
Adrian Egli ◽  
Jonathan Gubbay ◽  
Luiz Lisboa ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
H1n1 Infection ◽  
Transplant Recipients ◽  
Influenza A H1n1 ◽  
Solid Organ Transplant Recipients

scholarly journals Cell-Mediated and Humoral Immune Response to 2-Dose SARS-CoV2 mRNA vaccination in Immunocompromised patient population

2021 ◽  
Author(s):  
Muthukumar Ramanathan ◽  
Kanagavel Murugesan ◽  
Lu M Yang ◽  
Cristina Costales ◽  
Philip L Bulterys ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Transplant Recipients ◽  
Humoral Immune ◽  
Cell Mediated Immune Response ◽  
Solid Organ Transplant Recipients

Characterization of cell-mediated and humoral immune responses to SARS-CoV2 mRNA vaccine has implications for protective immunity in immunocompromised patients. However, studies have demonstrated poor humoral response to SARS-CoV2 mRNA vaccine in immunocompromised patients and data on cellular immune response are currently lacking. Here we compared immune response after 2-dose vaccination in 100 immunocompromised patients (solid organ transplant recipients, hematologic malignancy, autoimmune condition, and primary immunodeficiency) and 16 immunocompetent healthy healthcare workers. We find that 100% (CI=80.6-100%) of immunocompetent individuals show positive cell-mediated and humoral immune response post vaccination while only 50% (CI=40.4-59.6%) of immunocompromised patients show humoral immune response and 69% (CI=59.4-77.2%) have a positive cell-mediated immune response. 21% of immunocompromised patients have no humoral immune response or cell-mediated immune response and thus are likely vulnerable to SARS-CoV2 infection. Monitoring of immune response in immunocompromised populations, particularly in high-risk immunocompromised patients (solid organ transplant recipients, patients with severe autoimmunity, and those ≥50 years), with clinical IGRA and serological assay after vaccination may identify patients who may benefit from revaccination or prophylactic monoclonal antibody therapy to prevent COVID-19 in this patient population

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