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2 pages, 175 KiB

Open AccessEditorial

Concluding Remarks for the Special Issue on RNA Viruses and Antibody Response

by Yiu-Wing KAM

Viruses 2023, 15(5), 1214; https://doi.org/10.3390/v15051214 - 22 May 2023

Cited by 1 | Viewed by 1361

Abstract

Infectious diseases represent one of the major public health concerns on the global level [...] Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

Research

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12 pages, 965 KiB

Open AccessArticle

Validation of N Protein Antibodies to Diagnose Previous SARS-CoV-2 Infection in a Large Cohort of Healthcare Workers: Use of Roche Elecsys^® Immunoassay in the S Protein Vaccination Era

by Juan Francisco Delgado, Mònica Vidal, Germà Julià, Gema Navarro, Rosa María Serrano, Eva van den Eynde, Marta Navarro, Joan Calvet, Jordi Gratacós, Mateu Espasa and Pilar Peña

Viruses 2023, 15(4), 930; https://doi.org/10.3390/v15040930 - 7 Apr 2023

Cited by 1 | Viewed by 1769

Abstract

The aim of this study was to validate the detection of anti-nucleocapsid protein (N protein) antibodies for the diagnosis of SARS-CoV-2 infection in light of the fact that most COVID-19 vaccines use the spike (S) protein as the antigen. Here, 3550 healthcare workers [...] Read more.

The aim of this study was to validate the detection of anti-nucleocapsid protein (N protein) antibodies for the diagnosis of SARS-CoV-2 infection in light of the fact that most COVID-19 vaccines use the spike (S) protein as the antigen. Here, 3550 healthcare workers (HCWs) were enrolled from May 2020 (when no S protein vaccines were available). We defined SARS-CoV-2 infection if HCWs were found to be positive by RT-PCR or found to be positive in at least two different serological immunoassays. Serum samples from Biobanc I3PT-CERCA were analyzed by Roche Elecsys^® (N protein) and Vircell IgG (N and S proteins) immunoassays. Discordant samples were reanalyzed with other commercial immunoassays. Roche Elecsys^® showed the positivity of 539 (15.2%) HCWs, 664 (18.7%) were found to be positive by Vircell IgG immunoassays, and 164 samples (4.6%) showed discrepant results. According to our SARS-CoV-2 infection criteria, 563 HCWs had SARS-CoV-2 infection. The Roche Elecsys^® immunoassay has a sensitivity, specificity, accuracy, and concordance with the presence of infection of 94.7%, 99.8%, 99.3%, and 0.96, respectively. Similar results were observed in a validation cohort of vaccinated HCWs. We conclude that the Roche Elecsys^® SARS-CoV-2 N protein immunoassay demonstrated good performance in diagnosing previous SARS-CoV-2 infection in a large cohort of HCWs. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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11 pages, 1607 KiB

Open AccessCommunication

Correlation of SARS-CoV-2 Neutralization with Antibody Levels in Vaccinated Individuals

by Shazeda Haque Chowdhury, Sean Riley, Riley Mikolajczyk, Lauren Smith, Lakshmanan Suresh and Amy Jacobs

Viruses 2023, 15(3), 793; https://doi.org/10.3390/v15030793 - 21 Mar 2023

Cited by 1 | Viewed by 1944

Abstract

Neutralizing antibody titers are an important measurement of the effectiveness of vaccination against SARS-CoV-2. Our laboratory has set out to further verify the functionality of these antibodies by measuring the neutralization capacity of patient samples against infectious SARS-CoV-2. Samples from patients from Western [...] Read more.

Neutralizing antibody titers are an important measurement of the effectiveness of vaccination against SARS-CoV-2. Our laboratory has set out to further verify the functionality of these antibodies by measuring the neutralization capacity of patient samples against infectious SARS-CoV-2. Samples from patients from Western New York who had been vaccinated with the original Moderna and Pfizer vaccines (two doses) were tested for neutralization of both Delta (B.1.617.2) and Omicron (BA.5). Strong correlations between antibody levels and neutralization of the delta variant were attained; however, antibodies from the first two doses of the vaccines did not have good neutralization coverage of the subvariant omicron BA.5. Further studies are ongoing with local patient samples to determine correlation following updated booster administration. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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12 pages, 1130 KiB

Open AccessArticle

Hemagglutinin Antibodies in the Polish Population during the 2019/2020 Epidemic Season

by Karol Szymański, Katarzyna Kondratiuk, Ewelina Hallmann, Anna Poznańska and Lidia B. Brydak

Viruses 2023, 15(3), 760; https://doi.org/10.3390/v15030760 - 16 Mar 2023

Cited by 2 | Viewed by 1453

Abstract

The aim of the study was to determine the level of antibodies against hemagglutinin of influenza viruses in the serum of subjects belonging to seven different age groups in the 2019/2020 epidemic season. The level of anti-hemagglutinin antibodies was tested using the hemagglutination [...] Read more.

The aim of the study was to determine the level of antibodies against hemagglutinin of influenza viruses in the serum of subjects belonging to seven different age groups in the 2019/2020 epidemic season. The level of anti-hemagglutinin antibodies was tested using the hemagglutination inhibition (HAI) test. The tests included 700 sera from all over Poland. Their results confirmed the presence of antibodies against the following influenza virus antigens: A/Brisbane/02/2018 (H1N1)pdm09 (48% of samples), A/Kansas/14/2017/ (H3N2) (74% of samples), B/Colorado/06/ 2017 Victoria line (26% of samples), and B/Phuket/3073/2013 Yamagata line (63% of samples). The level of antibodies against hemagglutinin varied between the age groups. The highest average (geometric mean) antibody titer (68.0) and the highest response rate (62%) were found for the strain A/Kansas/14/2017/ (H3N2). During the epidemic season in Poland, only 4.4% of the population was vaccinated. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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15 pages, 922 KiB

Open AccessArticle

T Cell Responses Correlate with Self-Reported Disease Severity and Neutralizing Antibody Responses Predict Protection against SARS-CoV-2 Breakthrough Infection

by Zhen Zhao, Attila Kumanovics, Tanzy Love, Stacy E. F. Melanson, Qing H. Meng, Alan H. B. Wu, Joesph Wiencek, Fred S. Apple, Caitlin R. Ondracek, David D. Koch, Robert H. Christenson and Yan Victoria Zhang

Viruses 2023, 15(3), 709; https://doi.org/10.3390/v15030709 - 9 Mar 2023

Cited by 3 | Viewed by 2963

Abstract

Objectives: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. Design and Methods: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and [...] Read more.

Objectives: The objective of this prospective study was to investigate the role of adaptive immunity in response to SARS-CoV-2 vaccines. Design and Methods: A cohort of 677 vaccinated individuals participated in a comprehensive survey of their vaccination status and associated side effects, and donated blood to evaluate their adaptive immune responses by neutralizing antibody (NAb) and T cell responses. The cohort then completed a follow-up survey to investigate the occurrence of breakthrough infections. Results: NAb levels were the highest in participants vaccinated with Moderna, followed by Pfizer and Johnson & Johnson. NAb levels decreased with time after vaccination with Pfizer and Johnson & Johnson. T cell responses showed no significant difference among the different vaccines and remained stable up to 10 months after the study period for all vaccine types. In multivariate analyses, NAb responses (<95 U/mL) predicted breakthrough infection, whereas previous infection, the type of vaccine, and T cell responses did not. T cell responses to viral epitopes (<0.120 IU/mL) showed a significant association with the self-reported severity of COVID-19 disease. Conclusion: This study provides evidence that NAb responses to SARS-CoV-2 vaccination correlate with protection against infection, whereas the T cell memory responses may contribute to protection against severe disease but not against infection. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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10 pages, 670 KiB

Open AccessCommunication

Use of Oral Antivirals Ritonavir-Nirmatrelvir and Molnupiravir in Patients with Multiple Myeloma Is Associated with Low Rates of Severe COVID-19: A Single-Center, Prospective Study

by Vassiliki Spiliopoulou, Ioannis Ntanasis-Stathopoulos, Panagiotis Malandrakis, Maria Gavriatopoulou, Foteini Theodorakakou, Despina Fotiou, Magdalini Migkou, Maria Roussou, Evangelos Eleutherakis-Papaiakovou, Efstathios Kastritis, Meletios A. Dimopoulos and Evangelos Terpos

Viruses 2023, 15(3), 704; https://doi.org/10.3390/v15030704 - 8 Mar 2023

Cited by 12 | Viewed by 2216

Abstract

In patients with multiple myeloma (MM), SARS-CoV-2 infection has been associated with a severe clinical course and high mortality rates due to the concomitant disease- and treatment-related immunosuppression. Specific antiviral treatment involves viral replication control with monoclonal antibodies and antivirals, including molnupiravir and [...] Read more.

In patients with multiple myeloma (MM), SARS-CoV-2 infection has been associated with a severe clinical course and high mortality rates due to the concomitant disease- and treatment-related immunosuppression. Specific antiviral treatment involves viral replication control with monoclonal antibodies and antivirals, including molnupiravir and the ritonavir-boosted nirmatrelvir. This prospective study investigated the effect of these two agents on SARS-CoV-2 infection severity and mortality in patients with MM. Patients received either ritonavir-nirmatrelvir or molnupiravir. Baseline demographic and clinical characteristics, as well as levels of neutralizing antibodies (NAbs), were compared. A total of 139 patients was treated with ritonavir-nirmatrelvir while the remaining 30 patients were treated with molnupiravir. In total, 149 patients (88.2%) had a mild infection, 15 (8.9%) had a moderate infection, and five (3%) had severe COVID-19. No differences in the severity of COVID-19-related outcomes were observed between the two antivirals. Patients with severe disease had lower neutralizing antibody levels before the COVID-19 infection compared to patients with mild disease (p = 0.04). Regarding treatment, it was observed that patients receiving belantamab mafodotin had a higher risk of severe COVID-19 (p < 0.001) in the univariate analysis. In conclusion, ritonavir-nirmatrelvir and molnupiravirmay prevent severe disease in MM patients with SARS-CoV-2 infection. This prospective study indicated the comparable effects of the two treatment options, providing an insight for further research in preventing severe COVID-19 in patients with hematologic malignancies. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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24 pages, 5060 KiB

Open AccessArticle

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies

by Zhaobin Xu, Dongqing Wei, Hongmei Zhang and Jacques Demongeot

Viruses 2023, 15(2), 586; https://doi.org/10.3390/v15020586 - 20 Feb 2023

Cited by 7 | Viewed by 2409

Abstract

Infectious diseases such as SARS-CoV-2 pose a considerable threat to public health. Constructing a reliable mathematical model helps us quantitatively explain the kinetic characteristics of antibody-virus interactions. A novel and robust model is developed to integrate antibody dynamics with virus dynamics based on [...] Read more.

Infectious diseases such as SARS-CoV-2 pose a considerable threat to public health. Constructing a reliable mathematical model helps us quantitatively explain the kinetic characteristics of antibody-virus interactions. A novel and robust model is developed to integrate antibody dynamics with virus dynamics based on a comprehensive understanding of immunology principles. This model explicitly formulizes the pernicious effect of the antibody, together with a positive feedback stimulation of the virus–antibody complex on the antibody regeneration. Besides providing quantitative insights into antibody and virus dynamics, it demonstrates good adaptivity in recapturing the virus-antibody interaction. It is proposed that the environmental antigenic substances help maintain the memory cell level and the corresponding neutralizing antibodies secreted by those memory cells. A broader application is also visualized in predicting the antibody protection time caused by a natural infection. Suitable binding antibodies and the presence of massive environmental antigenic substances would prolong the protection time against breakthrough infection. The model also displays excellent fitness and provides good explanations for antibody selection, antibody interference, and self-reinfection. It helps elucidate how our immune system efficiently develops neutralizing antibodies with good binding kinetics. It provides a reasonable explanation for the lower SARS-CoV-2 mortality in the population that was vaccinated with other vaccines. It is inferred that the best strategy for prolonging the vaccine protection time is not repeated inoculation but a directed induction of fast-binding antibodies. Eventually, this model will inform the future construction of an optimal mathematical model and help us fight against those infectious diseases. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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11 pages, 565 KiB

Open AccessArticle

Safety and Efficacy of Outpatient Treatments for COVID-19: Real-Life Data from a Regionwide Cohort of High-Risk Patients in Tuscany, Italy (the FEDERATE Cohort)

by Tommaso Manciulli, Michele Spinicci, Barbara Rossetti, Roberta Maria Antonello, Filippo Lagi, Anna Barbiero, Flavia Chechi, Giuseppe Formica, Emanuela Francalanci, Mirco Alesi, Samuele Gaggioli, Giulia Modi, Sara Modica, Riccardo Paggi, Cecilia Costa, Alessandra Morea, Lorenzo Paglicci, Ilaria Rancan, Francesco Amadori, Agnese Tamborrino, Marta Tilli, Giulia Bandini, Alberto Moggi Pignone, Beatrice Valoriani, Francesca Montagnani, Mario Tumbarello, Pierluigi Blanc, Massimo Di Pietro, Luisa Galli, Donatella Aquilini, Antonella Vincenti, Spartaco Sani, Cesira Nencioni, Sauro Luchi, Danilo Tacconi, Lorenzo Zammarchi and Alessandro Bartoloni Show full author list Hide full author list

Viruses 2023, 15(2), 438; https://doi.org/10.3390/v15020438 - 5 Feb 2023

Cited by 13 | Viewed by 2719

Abstract

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in [...] Read more.

Early COVID-19 treatments can prevent progression to severe disease. However, real-life data are still limited, and studies are warranted to monitor the efficacy and tolerability of these drugs. We retrospectively enrolled outpatients receiving early treatment for COVID-19 in 11 infectious diseases units in the Tuscany region of Italy between 1 January and 31 March 2022, when Omicron sublineages BA.1 and BA.2 were circulating. Eligible COVID-19 patients were treated with sotrovimab (SOT), remdesivir (RMD), nirmatrelvir/ritonavir (NRM/r), or molnupiravir (MOL). We gathered demographic and clinical features, 28-day outcomes (hospitalization or death), and drugs tolerability. A total of 781 patients (median age 69.9, 66% boosted for SARS-CoV-2) met the inclusion criteria, of whom 314 were treated with SOT (40.2%), 205 with MOL (26.3%), 142 with RMD (18.2%), and 120 with NRM/r (15.4%). Overall, 28-day hospitalization and death occurred in 18/781 (2.3%) and 3/781 (0.3%), respectively. Multivariable Cox regression showed that patients receiving SOT had a reduced risk of meeting the composite outcome (28-day hospitalization and/or death) in comparison to the RMD cohort, while no significant differences were evidenced for the MOL and NRM/r groups in comparison to the RMD group. Other predictors of negative outcomes included cancer, chronic kidney disease, and a time between symptoms onset and treatment administration > 3 days. All treatments showed good safety and tolerability, with only eight patients (1%) whose treatment was interrupted due to intolerance. In the first Italian multicenter study presenting real-life data on COVID-19 early treatments, all regimens demonstrated good safety and efficacy. SOT showed a reduced risk of progression versus RMD. No significant differences of outcome were observed in preventing 28-day hospitalization and death among patients treated with RMD, MOL, and NRM/r. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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13 pages, 13803 KiB

Open AccessArticle

Mapping the Antibody Repertoires in Ferrets with Repeated Influenza A/H3 Infections: Is Original Antigenic Sin Really “Sinful”?

by Tal Einav, Martina Kosikova, Peter Radvak, Yuan-Chia Kuo, Hyung Joon Kwon and Hang Xie

Viruses 2023, 15(2), 374; https://doi.org/10.3390/v15020374 - 28 Jan 2023

Viewed by 2372

Abstract

The influenza-specific antibody repertoire is continuously reshaped by infection and vaccination. The host immune response to contemporary viruses can be redirected to preferentially boost antibodies specific for viruses encountered early in life, a phenomenon called original antigenic sin (OAS) that is suggested to [...] Read more.

The influenza-specific antibody repertoire is continuously reshaped by infection and vaccination. The host immune response to contemporary viruses can be redirected to preferentially boost antibodies specific for viruses encountered early in life, a phenomenon called original antigenic sin (OAS) that is suggested to be responsible for diminished vaccine effectiveness after repeated seasonal vaccination. Using a new computational tool called Neutralization Landscapes, we tracked the progression of hemagglutination inhibition antibodies within ferret antisera elicited by repeated influenza A/H3 infections and deciphered the influence of prior exposures on the de novo antibody response to evolved viruses. The results indicate that a broadly neutralizing antibody signature can nevertheless be induced by repeated exposures despite OAS induction. Our study offers a new way to visualize how immune history shapes individual antibodies within a repertoire, which may help to inform future universal influenza vaccine design. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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14 pages, 2320 KiB

Open AccessArticle

Assessment of Immunogenic and Antigenic Properties of Recombinant Nucleocapsid Proteins of Five SARS-CoV-2 Variants in a Mouse Model

by Alexandra Rak, Nikolay Gorbunov, Valeria Kostevich, Alexey Sokolov, Polina Prokopenko, Larisa Rudenko and Irina Isakova-Sivak

Viruses 2023, 15(1), 230; https://doi.org/10.3390/v15010230 - 13 Jan 2023

Cited by 8 | Viewed by 2150

Abstract

COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control of the spread of new variants can be achieved through targeting of conserved viral epitopes. In this regard, the SARS-CoV-2 nucleocapsid (N) protein, which is much [...] Read more.

COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control of the spread of new variants can be achieved through targeting of conserved viral epitopes. In this regard, the SARS-CoV-2 nucleocapsid (N) protein, which is much more conserved than the evolutionarily influenced spike protein (S), is a suitable antigen. The recombinant N protein can be considered not only as a screening antigen but also as a basis for the development of next-generation COVID-19 vaccines, but little is known about induction of antibodies against the N protein via different SARS-CoV-2 variants. In addition, it is important to understand how antibodies produced against the antigen of one variant can react with the N proteins of other variants. Here, we used recombinant N proteins from five SARS-CoV-2 strains to investigate their immunogenicity and antigenicity in a mouse model and to obtain and characterize a panel of hybridoma-derived monoclonal anti-N antibodies. We also analyzed the variable epitopes of the N protein that are potentially involved in differential recognition of antiviral antibodies. These results will further deepen our knowledge of the cross-reactivity of the humoral immune response in COVID-19. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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12 pages, 760 KiB

Open AccessArticle

Assessing the Pre-Vaccination Anti-SARS-CoV-2 IgG Seroprevalence among Residents and Staff in Nursing Home in Niigata, Japan, November 2020

by Keita Wagatsuma, Sayaka Yoshioka, Satoru Yamazaki, Ryosuke Sato, Wint Wint Phyu, Irina Chon, Yoshiki Takahashi, Hisami Watanabe and Reiko Saito

Viruses 2022, 14(11), 2581; https://doi.org/10.3390/v14112581 - 21 Nov 2022

Cited by 2 | Viewed by 2191

Abstract

An outbreak of coronavirus disease 2019 (COVID-19) occurred in a nursing home in Niigata, Japan, November 2020, with an attack rate of 32.0% (63/197). The present study was aimed at assessing the pre-vaccination seroprevalence almost half a year after the COVID-19 outbreak in [...] Read more.

An outbreak of coronavirus disease 2019 (COVID-19) occurred in a nursing home in Niigata, Japan, November 2020, with an attack rate of 32.0% (63/197). The present study was aimed at assessing the pre-vaccination seroprevalence almost half a year after the COVID-19 outbreak in residents and staff in the facility, along with an assessment of the performance of the enzyme-linked immunosorbent assay (ELISA) and the chemiluminescent immunoassay (CLIA), regarding test seropositivity and seronegativity in detecting immunoglobulin G (IgG) anti-severe acute respiratory syndrome 2 (SARS-CoV-2) antibodies (anti-nucleocapsid (N) and spike (S) proteins). A total of 101 people (30 reverse transcription PCR (RT-PCR)-positive and 71 RT-PCR-negative at the time of the outbreak in November 2020) were tested for anti-IgG antibody titers in April 2021, and the seroprevalence was approximately 40.0–60.0% for residents and 10.0–20.0% for staff, which was almost consistent with the RT-PCR test results that were implemented during the outbreak. The seropositivity for anti-S antibodies showed 90.0% and was almost identical to the RT-PCR positives even after approximately six months of infections, suggesting that the anti-S antibody titer test is reliable for a close assessment of the infection history. Meanwhile, seropositivity for anti-N antibodies was relatively low, at 66.7%. There was one staff member and one resident that were RT-PCR-negative but seropositive for both anti-S and anti-N antibody, indicating overlooked infections despite periodical RT-PCR testing at the time of the outbreak. Our study indicated the impact of transmission of SARS-CoV-2 in a vulnerable elderly nursing home in the pre-vaccination period and the value of a serological study to supplement RT-PCR results retrospectively. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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17 pages, 1046 KiB

Open AccessArticle

Characterizing Longitudinal Antibody Responses in Recovered Individuals Following COVID-19 Infection and Single-Dose Vaccination: A Prospective Cohort Study

by Andrea D. Olmstead, Aidan M. Nikiforuk, Sydney Schwartz, Ana Citlali Márquez, Tahereh Valadbeigy, Eri Flores, Monika Saran, David M. Goldfarb, Althea Hayden, Shazia Masud, Shannon L. Russell, Natalie Prystajecky, Agatha N. Jassem, Muhammad Morshed and Inna Sekirov

Viruses 2022, 14(11), 2416; https://doi.org/10.3390/v14112416 - 31 Oct 2022

Cited by 5 | Viewed by 2237

Abstract

Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. Methods: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, [...] Read more.

Background: Investigating antibody titers in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time. Methods: Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of qPCR-confirmed, COVID-19 recovered individuals (k = 57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n = 341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qPCR performed on self-collected nasopharyngeal specimens. Results: Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14–56 days post-vaccination (p < 0.001) and vaccination prevented waning (regression coefficient, B = 1.66 [95%CI: 1.45–3.46]); while decline of nucleocapsid antibodies over time was observed (regression coefficient, B = −0.24 [95%CI: −1.2-(−0.12)]). A positive association was found between COVID-19 vaccination and endemic human β-coronavirus IgG titer 14–56 days post vaccination (OC43, p = 0.02 & HKU1, p = 0.02). On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45–3.46) adjusting for age, biological sex, and time since infection. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals. Conclusions: Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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10 pages, 1741 KiB

Open AccessCommunication

Enhancing the Immunogenicity of RBD Protein Variants through Amino Acid E484 Mutation in SARS-CoV-2

by Zhikai Zhang, Xuan Wan, Xinyue Li, Shaoxi Cai and Chengsong Wan

Viruses 2022, 14(9), 2020; https://doi.org/10.3390/v14092020 - 13 Sep 2022

Cited by 2 | Viewed by 2007

Abstract

In the context of the COVID-19 pandemic, conducting antibody testing and vaccination is critical. In particular, the continued evolution of SARS-CoV-2 raises concerns about the effectiveness of vaccines currently in use and the activity of neutralizing antibodies. Here, we used the Escherichia coli [...] Read more.

In the context of the COVID-19 pandemic, conducting antibody testing and vaccination is critical. In particular, the continued evolution of SARS-CoV-2 raises concerns about the effectiveness of vaccines currently in use and the activity of neutralizing antibodies. Here, we used the Escherichia coli expression system to obtain nine different SARS-CoV-2 RBD protein variants, including six single-point mutants, one double-point mutant, and two three-point mutants. Western blotting results show that nine mutants of the RBD protein had strong antigenic activity in vitro. The immunogenicity of all RBD proteins was detected in mice to screen for protein mutants with high immunogenicity. The results show that the mutants E484K, E484Q, K417T-E484K-N501Y, and K417N-E484K-N501Y, especially the former two, had better immunogenicity than the wild type. This suggests that site E484 has a significant impact on the function of the RBD protein. Our results demonstrate that recombinant RBD protein expressed in E. coli can be an effective tool for the development of antibody detection methods and vaccines. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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16 pages, 5562 KiB

Open AccessArticle

Chikungunya Virus E2 Structural Protein B-Cell Epitopes Analysis

by João Paulo da Cruz Silva, Marielton dos Passos Cunha, Shahab Zaki Pour, Vitor Renaux Hering, Daniel Ferreira de Lima Neto and Paolo Marinho de Andrade Zanotto

Viruses 2022, 14(8), 1839; https://doi.org/10.3390/v14081839 - 22 Aug 2022

Cited by 5 | Viewed by 3053

Abstract

The Togaviridae family comprises a large and diverse group of viruses responsible for recurrent outbreaks in humans. Within this family, the Chikungunya virus (CHIKV) is an important Alphavirus in terms of morbidity, mortality, and economic impact on humans in different regions of the [...] Read more.

The Togaviridae family comprises a large and diverse group of viruses responsible for recurrent outbreaks in humans. Within this family, the Chikungunya virus (CHIKV) is an important Alphavirus in terms of morbidity, mortality, and economic impact on humans in different regions of the world. The objective of this study was to perform an IgG epitope recognition of the CHIKV’s structural proteins E2 and E3 using linear synthetic peptides recognized by serum from patients in the convalescence phase of infection. The serum samples used were collected in the state of Sergipe, Brazil in 2016. Based on the results obtained using immunoinformatic predictions, synthetic B-cell peptides corresponding to the epitopes of structural proteins E2 and E3 of the CHIKV were analyzed by the indirect peptide ELISA technique. Protein E2 was the main target of the immune response, and three conserved peptides, corresponding to peptides P3 and P4 located at Domain A and P5 at the end of Domain B, were identified. The peptides P4 and P5 were the most reactive and specific among the 11 epitopes analyzed and showed potential for use in serological diagnostic trials and development and/or improvement of the Chikungunya virus diagnosis and vaccine design. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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5 pages, 540 KiB

Open AccessCommunication

SARS-CoV-2 Omicron Variant Neutralization after Third Dose Vaccination in PLWH

by Alessandra Vergori, Alessandro Cozzi-Lepri, Giulia Matusali, Francesca Colavita, Stefania Cicalini, Paola Gallì, Anna Rosa Garbuglia, Marisa Fusto, Vincenzo Puro, Fabrizio Maggi, Enrico Girardi, Francesco Vaia and Andrea Antinori

Viruses 2022, 14(8), 1710; https://doi.org/10.3390/v14081710 - 3 Aug 2022

Cited by 17 | Viewed by 2192

Abstract

The aim was to measure neutralizing antibody levels against the SARS-CoV-2 Omicron (BA.1) variant in serum samples obtained from vaccinated PLWH and healthcare workers (HCW) and compare them with those against the Wuhan-D614G (W-D614G) strain, before and after the third dose of a [...] Read more.

The aim was to measure neutralizing antibody levels against the SARS-CoV-2 Omicron (BA.1) variant in serum samples obtained from vaccinated PLWH and healthcare workers (HCW) and compare them with those against the Wuhan-D614G (W-D614G) strain, before and after the third dose of a mRNA vaccine. We included 106 PLWH and 28 HCWs, for a total of 134 participants. Before the third dose, the proportion of participants with undetectable nAbsT against BA.1 was 88% in the PLWH low CD4 nadir group, 80% in the high nadir group and 100% in the HCW. Before the third dose, the proportion of participants with detectable nAbsT against BA.1 was 12% in the PLWH low nadir group, 20% in the high nadir group and 0% in HCW, respectively. After 2 weeks from the third dose, 89% of the PLWH in the low nadir group, 100% in the high nadir group and 96% of HCW elicited detectable nAbsT against BA.1. After the third dose, the mean log2 nAbsT against BA.1 in the HCW and PLWH with a high nadir group was lower than that seen against W-D614G (6.1 log2 (±1.8) vs. 7.9 (±1.1) and 6.4 (±1.3) vs. 8.6 (±0.8)), respectively. We found no evidence of a different level of nAbsT neutralization by BA.1 vs. W-D614G between PLWH with a high CD4 nadir and HCW (0.40 (−1.64, 2.43); p = 0.703). Interestingly, in PLWH with a low CD4 nadir, the mean log2 difference between nAbsT against BA.1 and W-D614G was smaller in those with current CD4 counts 201–500 vs. those with CD4 counts < 200 cells/mm³ (−0.80 (−1.52, −0.08); p = 0.029), suggesting that in this target population with a low CD4 nadir, current CD4 count might play a role in diversifying the level of SARS-CoV-2 neutralization. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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11 pages, 259 KiB

Open AccessReview

Understanding the SARS-CoV-2 Virus Neutralizing Antibody Response: Lessons to Be Learned from HIV and Respiratory Syncytial Virus

by Nigel J. Dimmock and Andrew J. Easton

Viruses 2023, 15(2), 504; https://doi.org/10.3390/v15020504 - 11 Feb 2023

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Abstract

The SARS-CoV-2 pandemic commenced in 2019 and is still ongoing. Neither infection nor vaccination give long-lasting immunity and, here, in an attempt to understand why this might be, we have compared the neutralizing antibody responses to SARS-CoV-2 with those specific for human immunodeficiency [...] Read more.

The SARS-CoV-2 pandemic commenced in 2019 and is still ongoing. Neither infection nor vaccination give long-lasting immunity and, here, in an attempt to understand why this might be, we have compared the neutralizing antibody responses to SARS-CoV-2 with those specific for human immunodeficiency virus type 1 (HIV-1) and respiratory syncytial virus (RSV). Currently, most of the antibodies specific for the SARS-CoV-2 S protein map to three broad antigenic sites, all at the distal end of the S trimer (receptor-binding site (RBD), sub-RBD and N-terminal domain), whereas the structurally similar HIV-1 and the RSV F envelope proteins have six antigenic sites. Thus, there may be several antigenic sites on the S trimer that have not yet been identified. The epitope mapping, quantitation and longevity of the SARS-CoV-2 S-protein-specific antibodies produced in response to infection and those elicited by vaccination are now being reported for specific groups of individuals, but much remains to be determined about these aspects of the host–virus interaction. Finally, there is a concern that the SARS-CoV-2 field may be reprising the HIV-1 experience, which, for many years, used a virus for neutralization studies that did not reflect the neutralizability of wild-type HIV-1. For example, the widely used VSV-SARS-CoV-2-S protein pseudotype has 10-fold more S trimers per virion and a different configuration of the trimers compared with the SARS-CoV-2 wild-type virus. Clarity in these areas would help in advancing understanding and aid countermeasures of the SARS-CoV-2 pandemic. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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19 pages, 1307 KiB

Open AccessSystematic Review

Convalescent Plasma Therapy for COVID-19: A Systematic Review and Meta-Analysis on Randomized Controlled Trials

by Charalampos Filippatos, Ioannis Ntanasis-Stathopoulos, Kalliopi Sekeri, Anastasios Ntanasis-Stathopoulos, Maria Gavriatopoulou, Theodora Psaltopoulou, George Dounias, Theodoros N. Sergentanis and Evangelos Terpos

Viruses 2023, 15(3), 765; https://doi.org/10.3390/v15030765 - 16 Mar 2023

Cited by 15 | Viewed by 2885

Abstract

Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess [...] Read more.

Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). Methods: A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality [RR = 0.98, 95% CI (0.91, 1.06)] or improved 28-day secondary outcomes, such as hospital discharge [RR = 1.00, 95% CI (0.97, 1.03)], ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI (0.98, 1.05) and RR = 1.06, 95% CI (0.95, 1.17), respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care [RR = 0.74, 95% CI (0.56, 0.99)]. Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions) [RR = 0.92, 95% CI (0.85, 0.99)] based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Conclusions: Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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