Viruses

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16 pages, 4632 KiB

Open AccessArticle

Fast-Track Discovery of SARS-CoV-2-Neutralizing Antibodies from Human B Cells by Direct Functional Screening

by Matthias Hillenbrand, Christoph Esslinger, Jemima Seidenberg, Marcel Weber, Andreas Zingg, Catherine Townsend, Barbara Eicher, Justina Rutkauskaite, Peggy Riese, Carlos A. Guzman, Karsten Fischer and Simone Schmitt

Viruses 2024, 16(3), 339; https://doi.org/10.3390/v16030339 - 22 Feb 2024

Viewed by 1068

Abstract

As the COVID-19 pandemic revealed, rapid development of vaccines and therapeutic antibodies are crucial to guarantee a quick return to the status quo of society. In early 2020, we deployed our droplet microfluidic single-cell-based platform DROPZYLLA^® for the generation of cognate antibody [...] Read more.

As the COVID-19 pandemic revealed, rapid development of vaccines and therapeutic antibodies are crucial to guarantee a quick return to the status quo of society. In early 2020, we deployed our droplet microfluidic single-cell-based platform DROPZYLLA^® for the generation of cognate antibody repertoires of convalescent COVID-19 donors. Discovery of SARS-CoV-2-specific antibodies was performed upon display of antibodies on the surface of HEK293T cells by antigen-specific sorting using binding to the SARS-CoV-2 spike and absence of binding to huACE2 as the sort criteria. This efficiently yielded antibodies within 3–6 weeks, of which up to 100% were neutralizing. One of these, MTX-COVAB, displaying low picomolar neutralization IC50 of SARS-CoV-2 and with a neutralization potency on par with the Regeneron antibodies, was selected for GMP manufacturing and clinical development in June 2020. MTX-COVAB showed strong efficacy in vivo and neutralized all identified clinically relevant variants of SARS-CoV-2 at the time of its selection. MTX-COVAB completed GMP manufacturing by the end of 2020, but clinical development was stopped when the Omicron variant emerged, a variant that proved to be detrimental to all monoclonal antibodies already approved. The present study describes the capabilities of the DROPZYLLA^® platform to identify antibodies of high virus-neutralizing capacity rapidly and directly. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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25 pages, 5876 KiB

Open AccessArticle

SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice

by María Florencia Pavan, Marina Bok, Rafael Betanzos San Juan, Juan Pablo Malito, Gisela Ariana Marcoppido, Diego Rafael Franco, Daniela Ayelen Militelo, Juan Manuel Schammas, Sara Elizabeth Bari, William Stone, Krisangel López, Danielle LaBrie Porier, John Anthony Muller, Albert Jonathan Auguste, Lijuan Yuan, Andrés Wigdorovitz, Viviana Gladys Parreño and Lorena Itat Ibañez

Viruses 2024, 16(2), 185; https://doi.org/10.3390/v16020185 - 25 Jan 2024

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Abstract

Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike [...] Read more.

Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, protection was associated with a significant reduction in virus replication in nasal turbinates and a reduction in virus load in the brain. Employing pseudovirus neutralization assays, we identified Nbs with neutralizing capacity against the Alpha, Beta, Delta, and Omicron variants, including a Nb capable of neutralizing all variants tested. Furthermore, cocktails of different Nbs performed better than individual Nbs at neutralizing two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest the potential of SARS-CoV-2 specific Nbs for intranasal treatment of COVID-19 encephalitis. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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11 pages, 767 KiB

Open AccessArticle

Neutralizing Antibodies against SARS-CoV-2: Importance of Comorbidities in Health Personnel against Reinfections

by Cruz Vargas-De-León, Mónica Alethia Cureño-Díaz, Ma. Isabel Salazar, Clemente Cruz-Cruz, Miguel Ángel Loyola-Cruz, Emilio Mariano Durán-Manuel, Edwin Rodrigo Zamora-Pacheco, Juan Carlos Bravata-Alcántara, Gustavo Esteban Lugo-Zamudio, Verónica Fernández-Sánchez, Juan Manuel Bello-López and Gabriela Ibáñez-Cervantes

Viruses 2023, 15(12), 2354; https://doi.org/10.3390/v15122354 - 30 Nov 2023

Cited by 1 | Viewed by 999

Abstract

One of the priority lines of action to contain the SARS-CoV-2 pandemic was vaccination programs for healthcare workers. However, with the emergence of highly contagious strains, such as the Omicron variant, it was necessary to know the serological status of health personnel to [...] Read more.

One of the priority lines of action to contain the SARS-CoV-2 pandemic was vaccination programs for healthcare workers. However, with the emergence of highly contagious strains, such as the Omicron variant, it was necessary to know the serological status of health personnel to make decisions for the application of reinforcements. The aim of this work was to determine the seroprevalence against SARS-CoV-2 in healthcare workers in a Mexican hospital after six months of the administration of the Pfizer-BioNTech vaccine (two doses, 4 weeks apart) and to investigate the association between comorbidities, response to the vaccine, and reinfections. Neutralizing antibodies against SARS-CoV-2 were determined using ELISA assays for 262 employees of Hospital Juárez de México with and without a history of COVID-19. A beta regression analysis was performed to study the associated comorbidities and their relationship with the levels of antibodies against SARS-CoV-2. Finally, an epidemiological follow-up was carried out to detect reinfections in this population. A significant difference in SARS-CoV-2 seroprevalence was observed in workers with a history of COVID-19 prior to vaccination compared to those without a history of the disease (MD: 0.961 and SD: 0.049; <0.001). Beta regression showed that workers with a history of COVID-19 have greater protection compared to those without a history of the infection. Neutralizing antibodies were found to be decreased in alcoholic and diabetic subjects (80.1%). Notably, eight cases of Omicron reinfections were identified, and gender and obesity were associated with the presence of reinfections (6.41 OR; 95% BCa CI: 1.15, 105.0). The response to the vaccine was influenced by the history of SARS-CoV-2 infection and associated comorbidities. The above highlights the importance of prioritizing this segment of the population for reinforcements in periods of less than one year to guarantee their effectiveness against new variants. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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11 pages, 797 KiB

Open AccessArticle

Effectiveness of Bivalent Omicron-Containing Booster Vaccines against SARS-CoV-2 Omicron Variant among Individuals with and without Prior SARS-CoV-2 Infection

by Kristin Widyasari, Jieun Jang, Taejoon Kang and Sunjoo Kim

Viruses 2023, 15(8), 1756; https://doi.org/10.3390/v15081756 - 17 Aug 2023

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Abstract

In this study, we evaluated the effectiveness of the bivalent mRNA COVID-19 vaccines against the Omicron variant in individuals with or without prior SARS-CoV-2 infection history. We assessed the SARS-CoV-2-specific neutralizing antibody in serum samples by surrogate virus neutralizing assay (sVNT) and determined [...] Read more.

In this study, we evaluated the effectiveness of the bivalent mRNA COVID-19 vaccines against the Omicron variant in individuals with or without prior SARS-CoV-2 infection history. We assessed the SARS-CoV-2-specific neutralizing antibody in serum samples by surrogate virus neutralizing assay (sVNT) and determined the serum’s neutralizing capacity against the Omicron BA.5 by a plaque reduction neutralizing test (PRNT50). The results of the sVNT assay demonstrate a higher percentage of inhibition of the serum samples from the infected group than from the uninfected group (p = 0.01) before the bivalent vaccination but a similarly high percentage of inhibition after the vaccination. Furthermore, the results of the PRNT50 assay demonstrate a higher neutralizing capacity of the serum samples against Omicron BA.5 in the infected group compared to the uninfected group, both before and after the bivalent vaccine administration (p < 0.01 and p = 0.02 for samples collected before and after the bivalent vaccination, respectively). A higher neutralizing capacity of the serum samples against BA.5 following bivalent vaccination compared to those before vaccination suggests the efficacy of bivalent mRNA COVID-19 vaccines in triggering an immune response against the Omicron variant, particularly BA.5, regardless of infection history. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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13 pages, 1123 KiB

Open AccessArticle

Efficacy, Pharmacokinetics, and Toxicity Profiles of a Broad Anti-SARS-CoV-2 Neutralizing Antibody

by Silvia Godínez-Palma, Edith González-González, Frida Ramírez-Villedas, Circe Garzón-Guzmán, Luis Vallejo-Castillo, Gregorio Carballo-Uicab, Gabriel Marcelín-Jiménez, Dany Batista, Sonia M. Pérez-Tapia and Juan C. Almagro

Viruses 2023, 15(8), 1733; https://doi.org/10.3390/v15081733 - 14 Aug 2023

Viewed by 1453

Abstract

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protects transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from an infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with [...] Read more.

We recently reported the isolation and characterization of an anti-SARS-CoV-2 antibody, called IgG-A7, that protects transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE-2) from an infection with SARS-CoV-2 Wuhan. We show here that IgG-A7 protected 100% of the transgenic mice infected with Delta (B.1.617.2) and Omicron (B.1.1.529) at doses of 0.5 and 5 mg/kg, respectively. In addition, we studied the pharmacokinetic (PK) profile and toxicology (Tox) of IgG-A7 in CD-1 mice at single doses of 100 and 200 mg/kg. The PK parameters at these high doses were proportional to the doses, with serum half-life of ~10.5 days. IgG-A7 was well tolerated with no signs of toxicity in urine and blood samples, nor in histopathology analyses. Tissue cross-reactivity (TCR) with a panel of mouse and human tissues showed no evidence of IgG-A7 interaction with the tissues of these species, supporting the PK/Tox results and suggesting that, while IgG-A7 has a broad efficacy profile, it is not toxic in humans. Thus, the information generated in the CD-1 mice as a PK/Tox model complemented with the mouse and human TCR, could be of relevance as an alternative to Non-Human Primates (NHPs) in rapidly emerging viral diseases and/or quickly evolving viruses such as SARS-CoV-2. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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14 pages, 1849 KiB

Open AccessArticle

Functional Characteristics of Serum Anti-SARS-CoV-2 Antibodies against Delta and Omicron Variants after Vaccination with Sputnik V

by Elizaveta I. Radion, Vladimir E. Mukhin, Alyona V. Kholodova, Ivan S. Vladimirov, Darya Y. Alsaeva, Anastasia S. Zhdanova, Natalya Y. Ulasova, Natalya V. Bulanova, Valentin V. Makarov, Anton A. Keskinov and Sergey M. Yudin

Viruses 2023, 15(6), 1349; https://doi.org/10.3390/v15061349 - 10 Jun 2023

Cited by 2 | Viewed by 1326

Abstract

Anti-SARS-CoV-2 vaccination leads to the production of neutralizing as well as non-neutralizing antibodies. In the current study, we investigated the temporal dynamics of both sides of immunity after vaccination with two doses of Sputnik V against SARS-CoV-2 variants Wuhan-Hu-1 SARS-CoV-2 G614-variant (D614G), B.1.617.2 [...] Read more.

Anti-SARS-CoV-2 vaccination leads to the production of neutralizing as well as non-neutralizing antibodies. In the current study, we investigated the temporal dynamics of both sides of immunity after vaccination with two doses of Sputnik V against SARS-CoV-2 variants Wuhan-Hu-1 SARS-CoV-2 G614-variant (D614G), B.1.617.2 (Delta), and BA.1 (Omicron). First, we constructed a SARS-CoV-2 pseudovirus assay to assess the neutralization activity of vaccine sera. We show that serum neutralization activity against BA.1 compared to D614G is decreased by 8.16-, 11.05-, and 11.16- fold in 1, 4, and 6 months after vaccination, respectively. Moreover, previous vaccination did not increase serum neutralization activity against BA.1 in recovered patients. Next, we used the ADMP assay to evaluate the Fc-mediated function of vaccine-induced serum antibodies. Our results show that the antibody-dependent phagocytosis triggered by S-proteins of the D614G, B.1.617.2 and BA.1 variants did not differ significantly in vaccinated individuals. Moreover, the ADMP efficacy was retained over up to 6 months in vaccine sera. Our results demonstrate differences in the temporal dynamics of neutralizing and non-neutralizing antibody functions after vaccination with Sputnik V. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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8 pages, 234 KiB

Open AccessCommunication

Clinical Efficacy of the Neutralizing Antibody Therapy Sotrovimab in Patients with SARS-CoV-2 Omicron BA.1 and BA.2 Subvariant Infections

by Naoyuki Miyashita, Yasushi Nakamori, Makoto Ogata, Naoki Fukuda, Akihisa Yamura, Yoshihisa Ishiura and Tomoki Ito

Viruses 2023, 15(6), 1300; https://doi.org/10.3390/v15061300 - 31 May 2023

Cited by 3 | Viewed by 1105

Abstract

Sotrovimab, an antibody active against severe acute respiratory syndrome coronavirus 2 that neutralizes antibodies, reduced the risk of COVID-19-related hospitalization or death in studies conducted before the emergence of the Omicron variant. The objective of this study is to evaluate the clinical efficacy [...] Read more.

Sotrovimab, an antibody active against severe acute respiratory syndrome coronavirus 2 that neutralizes antibodies, reduced the risk of COVID-19-related hospitalization or death in studies conducted before the emergence of the Omicron variant. The objective of this study is to evaluate the clinical efficacy of sotrovimab in patients with mild to moderate COVID-19 Omicron BA.1 and BA.2 subvariant infections using a propensity score matching method. The propensity score-matched cohort study population was derived from patients who received sotrovimab. We derived a comparator group from an age- and sex-matched population who were recuperating in a medical facility after COVID-19 infection or from elderly person entrance facilities during the same period who were eligible for but did not receive sotrovimab treatment. In total, 642 patients in the BA.1 subvariant group and 202 in the BA.2 subvariant group and matched individuals were analyzed. The outcome was the requirement for oxygen therapy. In the treatment group, 26 patients with the BA.1 subvariant and 8 patients with the BA.2 subvariant received oxygen therapy. The administration of oxygen therapy was significantly lower in the treatment group than in the control group (BA.1 subvariant group, 4.0% vs. 8.7%, p = 0.0008; BA.2 subvariant group, 4.0% vs. 9.9%, p = 0.0296). All these patients were admitted to our hospitals and received additional therapy and then recovered. No deaths were observed in either group. Our results demonstrate that the sotrovimab antibody treatment may be associated with a reduction in the requirement for oxygen therapy among high-risk patients with mild to moderate COVID-19 Omicron BA.1 and BA.2 subvariants. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

Review

Jump to: Research, Other

18 pages, 3698 KiB

Open AccessReview

An Overview of the Conventional and Novel Methods Employed for SARS-CoV-2 Neutralizing Antibody Measurement

by Vinícius Pinto Costa Rocha, Helenita Costa Quadros, Antônio Márcio Santana Fernandes, Luana Pereira Gonçalves, Roberto José da Silva Badaró, Milena Botelho Pereira Soares and Bruna Aparecida Souza Machado

Viruses 2023, 15(7), 1504; https://doi.org/10.3390/v15071504 - 5 Jul 2023

Cited by 4 | Viewed by 2165

Abstract

SARS-CoV-2 is the etiological agent of the coronavirus disease-19 (COVID-19) and is responsible for the pandemic that started in 2020. The virus enters the host cell through the interaction of its spike glycoprotein with the angiotensin converting enzyme-2 (ACE2) on the host cell’s [...] Read more.

SARS-CoV-2 is the etiological agent of the coronavirus disease-19 (COVID-19) and is responsible for the pandemic that started in 2020. The virus enters the host cell through the interaction of its spike glycoprotein with the angiotensin converting enzyme-2 (ACE2) on the host cell’s surface. Antibodies present an important role during the infection and pathogenesis due to many reasons, including the neutralization of viruses by binding to different spike epitopes. Therefore, measuring the neutralizing antibody titers in the whole population is important for COVID-19’s epidemiology. Different methods are described in the literature, and some have been used to validate the main vaccines used worldwide. In this review, we discuss the main methods used to quantify neutralizing antibody titers, their advantages and limitations, as well as new approaches to determineACE2/spike blockage by antibodies. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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Other

Jump to: Research, Review

9 pages, 1757 KiB

Open AccessBrief Report

Structure-Based Optimization of One Neutralizing Antibody against SARS-CoV-2 Variants Bearing the L452R Mutation

by Yamin Chen, Jialu Zha, Shiqi Xu, Jiang Shao, Xiaoshan Liu, Dianfan Li and Xiaoming Zhang

Viruses 2024, 16(4), 566; https://doi.org/10.3390/v16040566 - 5 Apr 2024

Viewed by 649

Abstract

Neutralizing antibodies (nAbs) play an important role against SARS-CoV-2 infections. Previously, we have reported one potent receptor binding domain (RBD)-binding nAb Ab08 against the SARS-CoV-2 prototype and a panel of variants, but Ab08 showed much less efficacy against the variants harboring the L452R [...] Read more.

Neutralizing antibodies (nAbs) play an important role against SARS-CoV-2 infections. Previously, we have reported one potent receptor binding domain (RBD)-binding nAb Ab08 against the SARS-CoV-2 prototype and a panel of variants, but Ab08 showed much less efficacy against the variants harboring the L452R mutation. To overcome the antibody escape caused by the L452R mutation, we generated several structure-based Ab08 derivatives. One derivative, Ab08-K99E, displayed the mostly enhanced neutralizing potency against the Delta pseudovirus bearing the L452R mutation compared to the Ab08 and other derivatives. Ab08-K99E also showed improved neutralizing effects against the prototype, Omicron BA.1, and Omicron BA.4/5 pseudoviruses. In addition, compared to the original Ab08, Ab08-K99E exhibited high binding properties and affinities to the RBDs of the prototype, Delta, and Omicron BA.4/5 variants. Altogether, our findings report an optimized nAb, Ab08-K99E, against SARS-CoV-2 variants and demonstrate structure-based optimization as an effective way for antibody development against pathogens. Full article

(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies 2.0)

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