Requirement for Fc Effector Mechanisms in the APOBEC3/Rfv3-Dependent Neutralizing Antibody Response

Antiretroviral neutralizing antibody (NAb) responses are often evaluated in the absence of Fc-dependent immune effectors. In murine Friend retrovirus infection, Apobec3/Rfv3 promotes a potent polyclonal NAb response. Here, we show that the Apobec3/Rfv3-dependent NAb response correlated with virus-specific IgG2 titers and that thein vivoneutralization potency of Apobec3/Rfv3-resistant antisera was dependent on activating Fcγ receptors but not complement. The data strengthen retroviral vaccine strategies aimed at eliciting NAbs that activate specific Fcγ receptors.

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N-Linked Glycosylation of GP5 of Porcine Reproductive and Respiratory Syndrome Virus Is Critically Important for Virus ReplicationIn Vivo

Journal of Virology ◽

10.1128/jvi.07067-11 ◽

2012 ◽

Vol 86 (18) ◽

pp. 9941-9951 ◽

Cited By ~ 40

Author(s):

Zuzhang Wei ◽

Tao Lin ◽

Lichang Sun ◽

Yanhua Li ◽

Xiaoming Wang ◽

...

Keyword(s):

Antibody Response ◽

Cultured Cells ◽

Neutralizing Antibody ◽

Respiratory Syndrome Virus ◽

Virus Infectivity ◽

Serum Samples ◽

Virus Life Cycle ◽

Glycosylation Sites ◽

High Level

It has been proposed that the N-linked glycan addition at certain sites in GP5 of porcine reproductive and respiratory syndrome virus (PRRSV) is important for production of infectious viruses and viral infectivity. However, such specific N-linked glycosylation sites do not exist in some field PRRSV isolates. This implies that the existence of GP5-associated glycanper seis not vital to the virus life cycle. In this study, we found that mutation of individual glycosylation sites at N30, N35, N44, and N51 in GP5 did not affect virus infectivity in cultured cells. However, the mutants carrying multiple mutations at N-linked glycosylation sites in GP5 had significantly reduced virus yields compared with the wild-type (wt) virus. As a result, no viremia and antibody response were detected in piglets that were injected with a mutant without all N-linked glycans in GP5. These results suggest that the N-linked glycosylation of GP5 is critically important for virus replicationin vivo. The study also showed that removal of N44-linked glycan from GP5 increased the sensitivity of mutant virus to convalescent-phase serum samples but did not elicit a high-level neutralizing antibody response to wt PRRSV. The results obtained from the present study have made significant contributions to better understanding the importance of glycosylation of GP5 in the biology of PRRSV.

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Identification of the critical attribute(s) of EBV gp350 antigen required for elicitation of a neutralizing antibody response in vivo

Vaccine ◽

10.1016/j.vaccine.2015.10.024 ◽

2015 ◽

Vol 33 (48) ◽

pp. 6771-6777 ◽

Cited By ~ 12

Author(s):

Esteban Servat ◽

Bodrey W. Ro ◽

Corinne Cayatte ◽

Lorraine Gemmell ◽

Chris Barton ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibody ◽

Critical Attribute

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The quantitative landscape of the neutralizing antibody response to SARS-CoV-2

10.1101/2020.09.25.20201996 ◽

2020 ◽

Author(s):

Pranesh Padmanabhan ◽

Rajat Desikan ◽

Narendra M Dixit

Keyword(s):

Clinical Trials ◽

Antibody Response ◽

Dose Response ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Virtual Patient ◽

Plasma Samples ◽

Response Curves

Neutralizing antibodies (NAbs) appear promising interventions against SARS-CoV-2 infection. Over 100 NAbs have been identified so far and several are in clinical trials. Yet, which NAbs would be the most potent remains unclear. Here, we analysed reported in vitro dose-response curves (DRCs) of >70 NAbs and estimated corresponding 50% inhibitory concentrations, slope parameters, and instantaneous inhibitory potentials (IIPs), presenting a comprehensive quantitative landscape of NAb responses to SARS-CoV-2. NAbs with high IIPs are likely to be potent. To assess the applicability of the landscape in vivo, we analysed available DRCs of NAbs from individual patients and found that the responses closely resembled the landscape. Further, we created virtual patient plasma samples by randomly sampling NAbs from the landscape and found that they recapitulated plasma dilution assays from convalescent patients. The landscape thus offers a facile tool for benchmarking NAbs and would aid the development of NAb-based therapies for SARS-CoV-2 infection.

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Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2 infection in humans

Cell Host & Microbe ◽

10.1016/j.chom.2021.04.015 ◽

2021 ◽

Author(s):

Kanika Vanshylla ◽

Veronica Di Cristanziano ◽

Franziska Kleipass ◽

Felix Dewald ◽

Philipp Schommers ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibody

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Single-dose BNT162b2 mRNA COVID-19 vaccine significantly boosts neutralizing antibody response in health care workers recovering from asymptomatic or mild natural SARS-CoV-2 infection

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2021.05.033 ◽

2021 ◽

Author(s):

Ilaria Vicenti ◽

Francesca Gatti ◽

Renzo Scaggiante ◽

Adele Boccuto ◽

Daniela Zago ◽

...

Keyword(s):

Health Care ◽

Single Dose ◽

Antibody Response ◽

Health Care Workers ◽

Neutralizing Antibody ◽

Care Workers

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SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

Nature Communications ◽

10.1038/s41467-021-23942-y ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nanda Kishore Routhu ◽

Narayanaiah Cheedarla ◽

Venkata Satish Bollimpelli ◽

Sailaja Gangadhara ◽

Venkata Viswanadh Edara ◽

...

Keyword(s):

Antibody Response ◽

Antibody Titer ◽

Neutralizing Antibodies ◽

Rhesus Macaques ◽

Neutralizing Antibody ◽

Significant Loss ◽

Lung Pathology ◽

Live Virus ◽

Suitable Candidate ◽

Immune Pathology

AbstractThere is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

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Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries

Cell Discovery ◽

10.1038/s41421-021-00295-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yongbing Pan ◽

Jianhui Du ◽

Jia Liu ◽

Hai Wu ◽

Fang Gui ◽

...

Keyword(s):

Phage Display ◽

Neutralizing Antibodies ◽

Variable Region ◽

Neutralizing Antibody ◽

Chain Gene ◽

Prophylactic Efficacy ◽

Heavy Chains ◽

Effective Interventions ◽

Phage Display Libraries

AbstractAs the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

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