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Paula NM, Joucoski E, Baura VA, Souza EM, Pedrosa FO, Gonçalves AG, Huergo LF. Symptomatology and IgG Levels before and after SARS-CoV-2 Omicron Breakthrough Infections in Vaccinated Individuals. Vaccines (Basel) 2024; 12:1149. [PMID: 39460316 PMCID: PMC11512233 DOI: 10.3390/vaccines12101149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 09/20/2024] [Accepted: 09/30/2024] [Indexed: 10/28/2024] Open
Abstract
(1) Background: After the COVID-19 pandemic, there is concern regarding the immunity of the population to SARS-CoV-2 variants, particularly the Omicron variant and its sub-lineages. (2) Methods: The study involved analyzing the immune response and symptomatology of 27 vaccinated individuals who were subsequently infected by Omicron sub-lineages. Blood samples were collected for serological analysis, including the detection of IgG antibodies reactive to the Nucleocapsid (N) and Spike (S) antigens of SARS-CoV-2. Additionally, participants were interviewed to assess the intensity of symptoms during the infection. (3) Results: Despite the high levels of anti-Spike IgG observed after vaccination, all participants were infected by Omicron sub-lineages. The most common symptoms reported by participants were fever or chills, sore throat, and cough. The levels of anti-Spike IgG found prior to infection did not correlate with symptom intensity post-infection. However, it was observed that high post-infection anti-Nucleocapsid IgG levels correlated with mild symptoms during the course of the disease, suggesting a potential role for anti-N antibodies in symptom intensity. (4) Conclusions: In line with previous studies, the high levels of IgG anti-Spike resulting from vaccination did not provide complete protection against infection by the Omicron variant. Additionally, our data suggest that anti-Nucleocapsid IgG titers are negatively correlated with the intensity of the symptoms during mild infections.
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Affiliation(s)
- Nigella M. Paula
- Setor Litoral, Federal University of Paraná—UFPR, Matinhos 83260-00, PR, Brazil; (N.M.P.); (E.J.); (A.G.G.)
- Graduated Program in Sciences-Biochemistry, Federal University of Paraná—UFPR, Curitiba 81530-00, PR, Brazil; (V.A.B.); (E.M.S.); (F.O.P.)
| | - Emerson Joucoski
- Setor Litoral, Federal University of Paraná—UFPR, Matinhos 83260-00, PR, Brazil; (N.M.P.); (E.J.); (A.G.G.)
| | - Valter A. Baura
- Graduated Program in Sciences-Biochemistry, Federal University of Paraná—UFPR, Curitiba 81530-00, PR, Brazil; (V.A.B.); (E.M.S.); (F.O.P.)
| | - Emanuel M. Souza
- Graduated Program in Sciences-Biochemistry, Federal University of Paraná—UFPR, Curitiba 81530-00, PR, Brazil; (V.A.B.); (E.M.S.); (F.O.P.)
| | - Fabio O. Pedrosa
- Graduated Program in Sciences-Biochemistry, Federal University of Paraná—UFPR, Curitiba 81530-00, PR, Brazil; (V.A.B.); (E.M.S.); (F.O.P.)
| | - Alan G. Gonçalves
- Setor Litoral, Federal University of Paraná—UFPR, Matinhos 83260-00, PR, Brazil; (N.M.P.); (E.J.); (A.G.G.)
- Graduated Program in Farmacy-Biochemistry, Federal University of Paraná—UFPR, Curitiba 81530-00, PR, Brazil
| | - Luciano F. Huergo
- Setor Litoral, Federal University of Paraná—UFPR, Matinhos 83260-00, PR, Brazil; (N.M.P.); (E.J.); (A.G.G.)
- Graduated Program in Sciences-Biochemistry, Federal University of Paraná—UFPR, Curitiba 81530-00, PR, Brazil; (V.A.B.); (E.M.S.); (F.O.P.)
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Pilati Campos IM, Marques M, Peiter GC, Brandalize APC, dos Santos MB, de Melo FF, Teixeira KN. Temporal pattern of humoral immune response in mild cases of COVID-19. World J Biol Chem 2023; 14:40-51. [PMID: 37034134 PMCID: PMC10080547 DOI: 10.4331/wjbc.v14.i2.40] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 12/08/2022] [Accepted: 02/02/2023] [Indexed: 03/24/2023] Open
Abstract
BACKGROUND Understanding the humoral response pattern of coronavirus disease 2019 (COVID-19) is one of the essential factors to better characterize the immune memory of patients, which allows understanding the temporality of reinfection, provides answers about the efficacy and durability of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and consequently helps in global public health and vaccination strategy. Among the patients who became infected with SARS-CoV-2, the majority who did not progress to death were those who developed the mild COVID-19, so understanding the pattern and temporality of the antibody response of these patients is certainly relevant.
AIM To investigate the temporal pattern of humoral response of specific immunoglobulin G (IgG) in mild cases of COVID-19.
METHODS Blood samples from 191 COVID-19 real-time reverse transcriptase-polymerase chain reaction (RT-qPCR)-positive volunteers from the municipality of Toledo/ Paraná/Brazil, underwent two distinct serological tests, enzyme-linked immunosorbent assay, and detection of anti-nucleocapsid IgG. Blood samples and clinicoepidemiological data of the volunteers were collected between November 2020 and February 2021. All assays were performed in duplicate and the manufacturers' recommendations were strictly followed. The data were statistically analyzed using multiple logistic regression; the variables were selected by applying the P < 0.05 criterion.
RESULTS Serological tests to detect specific IgG were performed on serum samples from volunteers who were diagnosed as being positive by RT-qPCR for COVID-19 or had disease onset in the time interval from less than 1 mo to 7 mo. The time periods when the highest number of participants with detectable IgG was observed were 1, 2 and 3 mo. It was observed that 9.42% of participants no longer had detectable IgG antibodies 1 mo only after being infected with SARS-CoV-2 and 1.57% were also IgG negative at less than 1 mo. At 5 mo, 3.14% of volunteers were IgG negative, and at 6 or 7 mo, 1 volunteer (0.52%) had no detectable IgG. During the period between diagnosis by RT-qPCR/symptoms onset and the date of collection for the study, no statistical significance was observed for any association analyzed. Moreover, considering the age category between 31 and 59 years as the exposed group, the P value was 0.11 for the category 31 to 59 years and 0.32 for the category 60 years or older, showing that in both age categories there was no association between the pair of variables analyzed. Regarding chronic disease, the exposure group consisted of the participants without any comorbidity, so the P value of 0.07 for the category of those with at least one chronic disease showed no association between the two variables.
CONCLUSION A temporal pattern of IgG response was not observed, but it is suggested that immunological memory is weak and there is no association between IgG production and age or chronic disease in mild COVID-19.
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Affiliation(s)
| | - Milena Marques
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
| | | | | | | | - Fabrício Freire de Melo
- Campus Anísio Teixeira, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
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Vidal LEL, Figueira-Mansur J, Jurgilas PB, Argondizzo APC, Pestana CP, Martins FO, da Silva Junior HC, Miguez M, Loureiro BO, Marques CDFS, Trinta KS, da Silva LBR, de Mello MB, da Silva ED, Bastos RC, Esteves G. Process development and characterization of recombinant nucleocapsid protein for its application on COVID-19 diagnosis. Protein Expr Purif 2023; 207:106263. [PMID: 36921810 PMCID: PMC10012136 DOI: 10.1016/j.pep.2023.106263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/10/2023] [Indexed: 03/15/2023]
Abstract
COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2). The nucleocapsid (N) protein from Sars-CoV-2 is a highly immunogenic antigen and responsible for genome packing. Serological assays are important tools to detect previous exposure to SARS-CoV-2, complement epidemiological studies, vaccine evaluation and also in COVID-19 surveillance. SARS-CoV-2 N (r2N) protein was produced in Escherichia coli, characterized, and the immunological performance was evaluated by enzyme-linked immunosorbent assay (ELISA) and beads-based array immunoassay. r2N protein oligomers were evidenced when it is associated to nucleic acid. Benzonase treatment reduced host nucleic acid associated to r2N protein, but crosslinking assay still demonstrates the presence of higher-order oligomers. Nevertheless, after RNase treatment the higher-order oligomers reduced, and dimer form increased, suggesting RNA contributes to the oligomer formation. Structural analysis revealed nucleic acid did not interfere with the thermal stability of the recombinant protein. Interestingly, nucleic acid was able to prevent r2N protein aggregation even with increasing temperature while the protein benzonase treated begin aggregation process above 55 °C. In immunological characterization, ELISA performed with 233 serum samples presented a sensitivity of 97.44% (95% Confidence Interval, CI, 91.04%, 99.69%) and a specificity of 98.71% (95% CI, 95.42%, 99.84%) while beads-based array immunoassay carried out with 217 samples showed 100% sensitivity and 98.6% specificity. The results exhibited an excellent immunological performance of r2N protein in serologic assays showing that, even in presence of nucleic acid, it can be used as a component of an immunoassay for the sensitive and specific detection of SARS-CoV-2 antibodies.
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Affiliation(s)
- Luãnna Elisa Liebscher Vidal
- Macromolecules Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil.
| | - Janaina Figueira-Mansur
- Recombinant Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Patrícia Barbosa Jurgilas
- Macromolecules Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Ana Paula Correa Argondizzo
- Recombinant Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Cristiane Pinheiro Pestana
- Recombinant Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Fernanda Otaviano Martins
- Recombinant Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Haroldo Cid da Silva Junior
- Immunological Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Mariana Miguez
- Recombinant Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Bernardo Oliveira Loureiro
- Diagnostic Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Christiane de Fátima Silva Marques
- Diagnostic Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Karen Soares Trinta
- Diagnostic Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Leila Botelho Rodrigues da Silva
- Diagnostic Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Marcelle Bral de Mello
- Diagnostic Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Edimilson Domingos da Silva
- Diagnostic Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Renata Chagas Bastos
- Macromolecules Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
| | - Gabriela Esteves
- Recombinant Technology Laboratory, Institute of Technology in Immunobiologicals (Bio-Manguinhos), Fundação Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, 21040-900, Brazil
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Population-Based Analysis of the Immunoglobulin G Response to Different COVID-19 Vaccines in Brazil. Vaccines (Basel) 2022; 11:vaccines11010021. [PMID: 36679871 PMCID: PMC9862407 DOI: 10.3390/vaccines11010021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 12/24/2022] Open
Abstract
(1) Background: COVID-19 vaccination in Brazil has been performed mostly with CoronaVac (Sinovac), ChAdOx1-S (AstraZeneca-University of Oxford) and BNT162b2 (Pfizer-BioNTech) vaccines. The titers of IgG antibodies reactive to the SARS-CoV-2 spike protein correlate with vaccine efficacy. Studies comparing vaccine immunogenicity in a real-world scenario are lacking. (2) Methods: We performed a population-based study to analyze the immunoglobulin G response to different COVID-19 vaccines. Citizens older than 18 years (n = 2376) provided personal data, a self-declaration of any previous COVID-19 positive tests and information regarding COVID-19 vaccination: the vaccine popular name and the date of each dose. Blood samples were collected and the levels of IgG reactive to SARS-CoV-2 antigens were determined and compared between different vaccine groups. (3) Results: The seroconversion for anti-spike IgG achieved > 95% by February 2022 and maintained stable until June 2022. Higher anti-spike IgG titers were detected in individuals vaccinated with BNT162b2, followed by ChAdOx1-S and CoronaVac. The anti-spike IgG response was negatively correlated with age and interval after the second dose for the BNT162b2 vaccine. Natural infections boosted anti-spike IgG in those individuals who completed primary vaccination with ChAdOx1-S and CoronaVac, but not with BNT162b2. The levels of anti-spike IgG increased with the number of vaccine doses administered. The application of BNT162b2 as a 3rd booster dose resulted in high anti-spike IgG antibody titers, despite the type of vaccine used during primary vaccination. (4) Conclusions: Our data confirmed the effectiveness of the Brazilian vaccination program. Of the vaccines used in Brazil, BNT162b2 performed better to elicit anti-spike protein IgG after primary vaccination and as a booster dose and thus should be recommended as a booster whenever available. A continuous COVID-19 vaccination program will be required to sustain anti-spike IgG antibodies in the population.
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Huergo LF, Paula NM, Gonçalves ACA, Kluge CHS, Marins PHSA, Camargo HSC, Sant’Ana TP, Farias LRP, Aldrighi JD, Lima ÊS, Jacotenski GT, Vargas LR, Costa G, Weissheimer KV, Nazário MG, Teixeira KN, Conzentino MS. SARS-CoV-2 Seroconversion in Response to Infection and Vaccination: a Time Series Local Study in Brazil. Microbiol Spectr 2022; 10:e0102622. [PMID: 35770982 PMCID: PMC9430992 DOI: 10.1128/spectrum.01026-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 06/08/2022] [Indexed: 11/25/2022] Open
Abstract
The investigation of antibodies raised against different severe acute respiratory syndrome coronavirus (SARS-CoV-2) antigens can help to determine the extent of previous SARS-CoV-2 infections in the population and track the humoral response to vaccination. Therefore, serological surveys can provide key information to better manage the pandemic and/or to implement the most effective vaccination program. Here we describe a time series anti-nucleocapsid, anti-spike IgG serological survey analysis in the city of Matinhos, PR, Brazil during the year of 2021. Seroconversion rates to the nucleocapsid antigen were not influenced by gender or age. The serological data support that the coronavirus disease 2019 (COVID-19) infection rate is ~50% higher than official numbers. Furthermore, by applying serological data, the corrected infection fatality rate was estimated to be lower than 2.4% in contrast with the official estimative of 3.6%. The rates of IgG reactive to spike antigen resembled the curve of the fraction the population that had taken the second vaccine dose. Up to 82% of spike seroconversion was detected in the end of 2021, confirming the effectiveness of the COVID-19 vaccination program in the city. This SARS-CoV-2 serological study unraveled the SARS-CoV-2 infection rates and the response to vaccination in the city of Matinhos. IMPORTANCE The investigation of antibodies raised against SARS-CoV-2 can help to determine the extent of previous SARS-CoV-2 infections and track the humoral response to vaccination. Here we describe a time series anti-nucleocapsid, anti-spike IgG serological survey in the city of Matinhos, PR, Brazil during the year of 2021. The data depicted the progression of SARS-CoV-2 infections in the city allowing the correction of the number of citizens who experienced COVID-19 and the disease fatality rate. The seroconversion rates to the spike antigen resembled the curve of the fraction of the population that had taken the second vaccine dose, thereby confirming the effectiveness of the COVID-19 vaccination program in the city.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Ênio S. Lima
- Setor Litoral, UFPR Matinhos, Matinhos, Paraná, Brazil
| | | | | | - Gisele Costa
- Setor Litoral, UFPR Matinhos, Matinhos, Paraná, Brazil
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