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Summary: SARS-CoV-2 mRNA vaccines provide protection against COVID-19, but concerns have arisen due to the emergence of variants that may reduce the efficacy of existing vaccines. This study investigated the binding and functional capacity of antibodies from recovered individuals and those induced by the Moderna mRNA1273 COVID-19 vaccine against SARS-CoV-2 variants of concern. While neutralizing responses to the variants decreased in both groups, the Fc-mediated responses differed. Antibodies from recovered individuals showed compromised interactions with Fc receptors, while vaccine-induced antibodies maintained their ability to interact with Fc receptors and mediate antibody effector functions. These findings suggest that mRNA vaccines may offer resilience in the humoral immune response and continue to provide protection against SARS-CoV-2 variants independent of neutralization.
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Delphine Planas et al.
Summary: The Omicron variant of SARS-CoV-2, identified in November 2021, has spread rapidly worldwide and shows resistance to most therapeutic monoclonal antibodies and vaccine-elicited antibodies. However, it can be neutralized by antibodies generated by a booster vaccine dose.
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Summary: The recent study by the SAVE/NIAID network shows that the B.1.1.529 Omicron variant causes milder lung disease in rodents, which is consistent with preliminary human clinical data.
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Yunlong Cao et al.
Summary: The Omicron variant of SARS-CoV-2 contains 15 mutations in the receptor-binding domain, leading to evasion of over 85% of tested neutralizing antibodies. Different epitope groups of neutralizing antibodies are affected to varying degrees by single mutations of Omicron. Antibodies targeting the conserved region of sarbecovirus remain most effective against Omicron.
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Lihong Liu et al.
Summary: The B.1.1.529/Omicron variant of SARS-CoV-2, initially detected in southern Africa, has rapidly spread globally and is expected to become dominant due to its enhanced transmissibility in the coming weeks. This variant poses a threat to the efficacy of current COVID-19 vaccines and antibody therapies due to its significant antibody resistance. Even individuals who have received vaccines and booster doses may have reduced neutralizing activity against B.1.1.529.
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Mickael Beraud et al.
Summary: A narrative review found that convalescent plasma infusions are well tolerated in COVID-19 patients, but do not seem to improve clinical outcomes in critically ill patients, and their potential benefits in immunocompromised patients remain uncertain.
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Guillaume Beaudoin-Bussieres et al.
Summary: Emerging evidence suggests that both neutralizing and Fc-mediated effector functions of antibodies are important for protection against SARS-CoV-2. A non-neutralizing antibody, CV3-13, with potent Fc-mediated effector functions, was found to bind to a specific epitope of the SARS-CoV-2 spike from a unique angle. In mouse experiments, the Fc-enhanced version of CV3-13 delayed virus spread, neuroinvasion, and death, and the combination of Fc-enhanced CV3-13 with a neutralizing antibody completely protected mice from lethal SARS-CoV-2 infection.
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Wenwe Li et al.
Summary: This study elucidates the structural basis and mode of action for two potent SARS-CoV-2 spike-neutralizing monoclonal antibodies. CV3-1 triggers shedding of the S1 subunit by binding to a loop structure in the receptor-binding domain (RBD), while CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit. Designing vaccine immunogens that incorporate conserved regions in the RBD and stem helix region could elicit pan-coronavirus protective immune responses.
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Oskar Ljungquist et al.
Summary: This study described the clinical and virological treatment outcomes of a group of severely immunosuppressed patients with COVID-19 who received convalescent plasma treatment. Results showed that some patients improved clinically after CCP treatment, but caution should be taken in interpreting the results due to limitations in the study design. Prospective, randomized trials are needed for further investigation.
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Summary: The successful development of COVID-19 vaccines has led to reduced morbidity and mortality. However, the emergence of viral variants has affected the efficacy of the vaccines, showing differences between two approved mRNA platforms, BNT162b2 and mRNA-1273. Understanding the differences in immune responses induced by these vaccines is important for determining their protective immunity.
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Frauke Seehusen et al.
Summary: SARS-CoV-2 not only affects the respiratory tract but also causes neurological symptoms and neuroinflammation. Using transgenic mice, it was found that various SARS-CoV-2 variants can spread to the central nervous system (CNS) following intranasal infection and primarily infect neurons. The inflammatory response is mainly driven by microglia and immune cells, and microglia may play a significant role in the pathology and viral effects of COVID-19.
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Sara Y. Tartof et al.
Summary: This study evaluated the effectiveness and durability of two and three doses of the BNT162b2 (Pfizer-BioNTech) mRNA vaccine against hospital and emergency department admissions due to the delta and omicron variants. The results showed that three doses of the vaccine provided high protection against both variants in the first 3 months after vaccination, but waning was observed against the omicron variant after 3 months. Additional doses of vaccines might be needed to maintain high levels of protection against future variants.
LANCET RESPIRATORY MEDICINE
(2022)
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Medicine, General & Internal
Takuya Tada et al.
Summary: This study found that the Omicron variant has significantly reduced sensitivity to neutralization by vaccines and vaccine-elicited antibodies. However, a booster immunization can enhance the neutralizing effect against Omicron. In addition, individuals with a history of prior SARS-CoV-2 infection showed increased neutralizing activity against Omicron. Different monoclonal antibodies showed varying effectiveness against the Omicron variant.
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Multidisciplinary Sciences
Alexandra Tauzin et al.
Summary: Solid organ transplant recipients (SOTRs) show weak humoral responses after the second dose of SARS-CoV-2 mRNA vaccine, but the third dose can boost these responses. However, neutralizing activity remains low, and the protective effect against severe outcomes in SOTRs is yet to be determined.
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Allison J. Greaney et al.
Summary: This study develops an "escape estimator" by aggregating deep mutational scanning data to predict the impact of viral mutations on antibody recognition and score the antigenic effect of mutation combinations. The scores from the estimator correlate with neutralization assays, highlighting the concerning antigenic properties of the Omicron variant.
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Alexandra Schafer et al.
Summary: The study shows that combined use of hu-mAbs is effective for prevention and therapy of SARS-CoV-2 infection, but in vivo protection is influenced by intact effector function.
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Zijun Wang et al.
Summary: The IgA response to SARS-CoV-2 was characterized in a cohort of 149 convalescent individuals after COVID-19 diagnosis. IgA responses in plasma generally correlated with IgG responses, and B cells producing IgM, IgG, and IgA were derived from common progenitor cells. Notably, IgA dimers were found to be 15 times more potent than IgA monomers against SARS-CoV-2, suggesting their potential value for protection and vaccine efficacy.
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Lise J. Estcourt et al.
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JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
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Immunology
Adi Gundlapalli et al.
Summary: There is a current lack of standardized SARS-CoV-2 quantitative IgG and neutralization assays, which hinders the comparison of results from different studies. Most studies have used in-house laboratory-developed tests with non-standardized reporting methods. It is vital to enhance interassay and interlaboratory validation and standardization in order to better understand immune responses and vaccine efficacy.
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Emma S. Winkler et al.
Summary: This study found that neutralizing human monoclonal antibodies in SARS-CoV-2-infected animals require Fc effector functions for optimal protection, reducing inflammation, improving respiratory mechanics, and being associated with diminished immune signaling and tissue repair.
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Romain Gasser et al.
Summary: Depletion of immunoglobulin M is associated with the most substantial loss of virus neutralization, followed by immunoglobulin G. This finding may have implications for designing more effective antibody-based COVID-19 therapies and explaining the increased susceptibility of autoimmune patients receiving therapies that inhibit the production of immunoglobulin M (IgM).
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Bronwyn M. Gunn et al.
Summary: Protective Ebola virus antibodies have neutralizing activity and stimulate innate immune effector functions. By analyzing survivor Fc effector profiles, researchers identified Fc variants with antibody-mediated complement deposition and moderate NK cell activity that showed complete protective activity in a stringent in vivo mouse model. This study emphasizes the importance of specific effector functions in antibody-mediated protection and provides a generalizable resource for therapeutic antibody design.
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Elsa Brunet-Ratnasingham et al.
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Maamoun Basheer et al.
Summary: This study examined the efficacy of convalescent plasma therapy on COVID-19 patients, demonstrating significant reduction in mortality and shorter hospitalization and time to negative PCR among moderate patients. Factors such as high BMI, elderly age, high CRP, and 4C-scores were found to correlate with disease severity and mortality. Convalescent plasma therapy also reduced inflammatory markers, especially in moderate COVID-19 patients.
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Stefania Dispinseri et al.
Summary: The study reveals that antibody responses to SARS-CoV-2 spike protein play a significant role in neutralization and protection against severe COVID-19, unaffected by heterologous boosting or common cold immunity, and can last for up to 8 months.
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Alexandra Tauzin et al.
Summary: A single dose of the BNT162b2 mRNA vaccine can be up to 90% effective, with boosted humoral and T cell responses in previously infected individuals. Therefore, spacing doses may help vaccinate more people in conditions of limited vaccine supply.
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Irfan Ullah et al.
Summary: Neutralizing antibodies are effective in treating COVID-19, but the mechanism of immune protection is not fully understood. Real-time imaging revealed that highly potent NAbs can prevent and resolve established infections when administered within three days. Both Fab and Fc effector functions of NAbs are essential for optimal efficacy against SARS-CoV-2.
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Rachel Yamin et al.
Summary: Monoclonal antibodies with optimized Fc domains show superior potency in preventing and treating COVID-19 in animal disease models, reducing the dose required for protection against SARS-CoV-2 challenge and for treating pre-infected animals. Selective engagement of activating Fc receptors results in improved efficacy, highlighting the importance of Fc receptor pathways in driving antibody-mediated antiviral immunity. These findings have implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function against COVID-19.
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Multidisciplinary Sciences
Zhiqiang Ku et al.
Summary: A newly engineered IgM neutralizing antibody, IgM-14, demonstrates over 230-fold higher potency in neutralizing SARS-CoV-2 compared to the parental IgG-14. IgM-14 also displays strong neutralizing activity against resistant virus variants and receptor-binding domain mutants, indicating its potential as an effective therapy for COVID-19.
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Biochemistry & Molecular Biology
Philippe Begin et al.
Summary: Convalescent plasma did not reduce the risk of intubation or death at 30 days in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.
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Medicine, General & Internal
Frederick K. Korley et al.
Summary: This study showed that administering Covid-19 convalescent plasma to high-risk outpatients within 1 week after symptom onset did not prevent disease progression.
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Madeleine F. Jennewein et al.
Summary: The study identified 14 neutralizing antibodies against SARS-CoV-2, with 3 able to cross-neutralize SARS-CoV-1. The in vivo protective potential of antibodies is regulated by neutralization potency and epitope specificity. The study also suggests that epitopes in S2 can be used as blueprints for designing immunogens capable of eliciting cross-neutralizing coronavirus antibodies.
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Guillaume Beaudoin-Bussieres et al.
Summary: Antibodies can engage specific receptors on effector cells and have functions beyond viral neutralization, such as antibody-dependent cellular cytotoxicity (ADCC), which plays an important role in protection against SARS-CoV-2 infections. By using a cell line expressing GFP-tagged SARS-CoV-2 spike, ADCC activity mediated by anti-SARS-CoV-2 Spike monoclonal antibodies or plasma from previously infected or vaccinated individuals can be measured in an optimized manner. Detailed information on the protocol can be found in Anand et al. (2021b).
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Jian Zheng et al.
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