Antibody response 6 months after the booster dose of Pfizer in previous recipients of CoronaVac.

The most widely used vaccines were messenger RNA (mRNA), viral vector, and inactivated virus with two-dose schedules. In Brazil, the CoronaVac (Sinovac) was the first vaccine approved for emergency use, and the third dose was administered, preferably, with the BNT162b2 vaccine. We evaluated antibody levels after 6 months of the booster dose with BNT162B2 in previous recipients of CoronaVac and whether a subsequent severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection enhances the antibody response. We analyze the humoral response (spike [S] IgM for the SARS-CoV-2 and IgG for the S and nucleocapsid [N] proteins) in samples collected before the third dose and 6 months after the third dose. The presence of antibodies was measured by using Abbott Architect i2000SR. The IgM and IgG antispikes were stimulated mainly 30 days after the third dose (30d/3D), with a decline over time. The IgG anti-N was stimulated predominantly in 90d/3D and 180d/3D. The N IgG levels were 50 and 35 times higher in the positive polymerase chain reaction (PCR) group in 90d/3D and 180d/3D, respectively. The S IgG titers were 1.5 times elevated in the positive PCR group, in 180d/3D. The BNT162b2 boosted the S IgG levels, decreasing after 60 days. The booster shot induced IgM and IgG antibodies against spike protein. Infection after vaccination increased antibodies against protein N.

Dynamics of SARS-CoV-2 Antibody Response to CoronaVac followed by Booster Dose of BNT162b2 Vaccine.

We evaluated the longitudinal dynamics of antibody response to the SARS-CoV-2 vaccine CoronaVac and the effect of a booster dose of BNT162b2 vaccine. We found a robust antibody response after the second dose of CoronaVac that wanes over time. The response was recovered by BNT162b2, which boosted anti-spike antibody titers.

Dynamics of antibody response to CoronaVac vaccine.

CoronaVac was the first vaccine approved in Brazil for use in healthcare workers (HCWs). However, there is limited information about it, with little long-term evidence on post-vaccination antibody persistence. This study evaluated the antibody response to SARS-CoV-2 in 1237 HCWs after the first (1D), second dose (2D), and 6 months postvaccination (6mA2D) with CoronaVac. The seropositivity was 88% at 1D, increasing to 99.8% at 2D, but decreasing to 97.9% at 6mA2D, which was also observed at the analyzed antibody levels. Interestingly, the levels in females were higher than males, and we found a positive correlation with previous SARS-CoV-2 infection. Participants with comorbidities had lower levels suggesting the need to monitor for a potential booster dose. Our findings suggest that CoronaVac induced a robust antibody response that wanes significantly over time. Further longitudinal studies are needed to identify whether the antibodies will decline or plateau at a lower level.

Influence of age, gender, previous SARS-CoV-2 infection, and pre-existing diseases in antibody response after COVID-19 vaccination: A review.

Vaccines induce specific long-term immunological memory against pathogens, preventing the worsening of diseases. The COVID-19 health emergency has caused more than 6 million deaths and started a race for vaccine development. Antibody response to COVID-19 vaccines has been investigated primarily in healthcare workers. The heterogeneity of immune responses and the behavior of this response in particular groups were still very little explored. In this review, we discuss whether antibody responses after vaccination are influenced by age, gender, previous SARS-CoV-2 infection, or pre-existing diseases.

Seroprevalence and factors associated with SARS-CoV-2 infection among education workers after the first wave: the first cross-sectional study in Brazil.

BACKGROUND: The school community was heavily impacted by the Covid-19 pandemic, especially with the long time of school closures. This study aimed to analyze the seroprevalence of SARS-CoV-2 antibodies and possible factors associated with seropositivity for COVID-19 in teachers and other school staff, and to estimate the fraction of asymptomatic individuals by sex and age group. METHODS: We conducted a serological survey of SARS-CoV-2 infections. An analytical cross-sectional study was conducted in Fortaleza, Brazil. Teachers and other staff members from pre-schools to universities of higher education to were investigated. RESULTS: A total of 1,901 professionals participated in the study, of which 1,021 were staff and 880 were teachers. The seroprevalence of SARS-CoV-2 was 8.0% (152/1901). In the seropositive group, 48.3% were asymptomatic. There was a predominance of women (68.4%); and, 47.1% of the participants were between 31 and 45 years old. There was an increase in prevalence with increasing age. An inverse relationship was found for education level: more professionals with less education tested positive for COVID-19. The presence of an infected person living in the same household was significantly associated with positive results for COVID-19 among the professionals. CONCLUSIONS: This is the first study to report the seroprevalence of IgG against SARS-CoV-2 in Brazilian educational staff after the first wave of the disease. In this study, the seroprevalence was much lower than that in the general population. During school reopening, a small fraction of school workers showed serologically detectable signs of SARS-CoV-2 exposure.

Circumventing the side effects of L-asparaginase.

L-asparaginase is an enzyme that catalyzes the degradation of asparagine and successfully used in the treatment of acute lymphoblastic leukemia. L-asparaginase toxicity is either related to hypersensitivity to the foreign protein or to a secondary L-glutaminase activity that causes inhibition of protein synthesis. PEGylated versions have been incorporated into the treatment protocols to reduce immunogenicity and an alternative L-asparaginase derived from Dickeya chrysanthemi is used in patients with anaphylactic reactions to the E. coli L-asparaginase. Alternative approaches commonly explore new sources of the enzyme as well as the use of protein engineering techniques to create less immunogenic, more stable variants with lower L-glutaminase activity. This article reviews the main strategies used to overcome L-asparaginase shortcomings and introduces recent tools that can be used to create therapeutic enzymes with improved features.

Expression of a recombinant bacterial L-asparaginase in human cells.

OBJECTIVE: L-Asparaginase (ASNase) is an enzyme used in the treatment of acute lymphoblastic leukemia (ALL). As the therapeutic ASNases has bacterial origin, severe side effects are associated with its use, among them hypersensitivity and inactivation of the enzyme. In this context, the objective of this work was to produce a recombinant ASNase of bacterial origin in human cells in order to determine the presence and consequences of potential post-translational modifications on the enzyme. RESULTS: Recombinant ASNase was expressed in human cells with a molecular weight of 60 kDa, larger than in Escherichia coli, which is 35 kDa. N-glycosylation analysis demonstrated that the increased molecular weight resulted from the addition of glycans to the protein by mammalian cells. The glycosylated ASNase presented in vitro activity at physiological pH and temperature. Given that glycosylation can act to reduce antigenicity by masking protein epitopes, our data may contribute to the development of an alternative ASNase in the treatment of ALL in patients who demonstrate side effects to currently marketed enzymes.

Seroprevalence and levels of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among medical students: possible associated factors in Northeastern Brazil / Soroprevalência e níveis de anticorpos anti-síndrome respiratória aguda grave coronavírus 2 (SARS-CoV-2) entre estudantes de medicina: possíveis fatores associados no Nordeste do Brasil

Objective: we evaluated the seroprevalence and levels of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among medical students and the possible associated factors. Methods: a survey was conducted using the data collected in November 2020 and February 2022 in Fortaleza, Northeast Brazil. A questionnaire was administered, and blood and nasopharyngeal swab samples were collected. The Abbott test was used for the assessment of humoral response to the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. The total antibodies were detected using a SARS-CoV-2 antibody test (Wodfo). Swab samples were subjected to qualitative detection of viral RNA. Chi-square test and multinomial logistic regression analysis were performed using SPSS and GraphPad Prism. Results: the seroprevalence rate in 2020 was 6.22% (40/643), and no difference in prevalence was observed between the semesters (p=0.520). The seroconversion rate was 51.1%. The seropositivity rates were 48.9% for N antibodies and 100% for S antibodies. The antibody response to N protein was higher in 2022 (p<0.001). Loss of smell was the most prevalent positive symptom (p=0.032). The adherence rate to protection measures was >75%. Most students reported a decrease in family income (63.7%), an increase in anxiety (82.6%), and a negative impact on their mental health (85.7%) regardless of the seroconversion status. The worst indicators of mental health quality were observed in students who attended classes up to the eighth semester (p<0.001). Conclusion: students showed lower immune response than the general population, with excellent adherence to the preventive and control measures. Medical schools played an important role in the formation but not transmission.

Objetivo: avaliamos a soroprevalência e os níveis de anticorpos anti-síndrome respiratória aguda grave coronavírus 2 (SARS-CoV-2) entre estudantes de medicina e os possíveis fatores associados. Métodos: foi realizada uma pesquisa com dados coletados em novembro de 2020 e fevereiro de 2022 em Fortaleza, Nordeste do Brasil. Um questionário foi aplicado e amostras de sangue e swab nasofaríngeo foram coletadas. O teste de Abbott foi utilizado para avaliação da resposta humoral às proteínas spike (S) e nucleocapsídeo (N) do SARS-CoV-2. Os anticorpos totais foram detectados usando um teste de anticorpos SARS-CoV-2 (Wodfo). Amostras de swab foram submetidas à detecção qualitativa de RNA viral. O teste qui-quadrado e a análise de regressão logística multinomial foram realizados utilizando SPSS e GraphPad Prism. Resultados: a taxa de soroprevalência em 2020 foi de 6,22% (40/643), e não foi observada diferença de prevalência entre os semestres (p=0,520). A taxa de soroconversão foi de 51,1%. As taxas de soropositividade foram de 48,9% para anticorpos N e 100% para anticorpos S. A resposta de anticorpos à proteína N foi maior em 2022 (p<0,001). A perda do olfato foi o sintoma positivo mais prevalente (p=0,032). A taxa de adesão às medidas de proteção foi >75%. A maioria dos estudantes relatou diminuição da renda familiar (63,7%), aumento da ansiedade (82,6%) e impacto negativo na saúde mental (85,7%), independentemente do estado de soroconversão. Os piores indicadores de qualidade em saúde mental foram observados nos alunos que frequentavam aulas até o oitavo semestre (p<0,001). Conclusão: os estudantes apresentaram resposta imunológica menor que a da população em geral, com excelente adesão às medidas preventivas e de controle. As escolas médicas desempenharam um papel importante na formação, mas não na transmissão.

Boosting half-life and effector functions of therapeutic antibodies by Fc-engineering: An interaction-function review.

Due mainly to their high level of affinity and specificity, therapeutic monoclonal antibodies (mAbs) have been frequently selected as treatment for cancer, autoimmune or chronic inflammatory diseases. Despite the increasing number of mAbs and related products in the biopharmaceutical market, they are still expensive, can cause undesired side effects, and eventually cause resistance. Antibody engineering, which emerged to overcome limitations faced by mAb therapy, has supported the development of modified mAbs for immunotherapy. As part of this approach, researchers have invested in obtaining antibody fragments, as well as in Fc region modifications, since interactions with Fc receptors influence an antibody's half-life and mechanism of action. Thus, Fc engineering results in antibodies with more desirable characteristics and functions for which they are intended, creating "fit-for-purpose" antibodies with reduced side effects. Furthermore, aglycosylated antibodies, produced in bacterial cultivation, have been an alternative to create new effector functional human immunotherapeutics, while reducing mAb therapy costs. This review highlights some features that enhance mAb performance, related to the improvement of antibody half-life and effector responses by both Fc-engineering and glycoengineering.

Seroprevalence and factors associated with SARS-CoV-2 infection among education workers after the first wave: the first cross-sectional study in Brazil

ABSTRACT Background: The school community was heavily impacted by the Covid-19 pandemic, especially with the long time of school closures. This study aimed to analyze the seroprevalence of SARS-CoV-2 antibodies and possible factors associated with seropositivity for COVID-19 in teachers and other school staff, and to estimate the fraction of asymptomatic individuals by sex and age group. Methods: We conducted a serological survey of SARS-CoV-2 infections. An analytical cross-sectional study was conducted in Fortaleza, Brazil. Teachers and other staff members from pre-schools to universities of higher education to were investigated. Results: A total of 1,901 professionals participated in the study, of which 1,021 were staff and 880 were teachers. The seroprevalence of SARS-CoV-2 was 8.0% (152/1901). In the seropositive group, 48.3% were asymptomatic. There was a predominance of women (68.4%); and, 47.1% of the participants were between 31 and 45 years old. There was an increase in prevalence with increasing age. An inverse relationship was found for education level: more professionals with less education tested positive for COVID-19. The presence of an infected person living in the same household was significantly associated with positive results for COVID-19 among the professionals. Conclusions: This is the first study to report the seroprevalence of IgG against SARS-CoV-2 in Brazilian educational staff after the first wave of the disease. In this study, the seroprevalence was much lower than that in the general population. During school reopening, a small fraction of school workers showed serologically detectable signs of SARS-CoV-2 exposure.