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We examined antibody and memory B cell responses longitudinally for â¼9-10 months after primary 2-dose SARS-CoV-2 mRNA vaccination and 3 months after a 3rd dose. Antibody decay stabilized between 6 and 9 months, and antibody quality continued to improve for at least 9 months after 2-dose vaccination. Spike- and RBD-specific memory B cells remained durable over time, and 40%-50% of RBD-specific memory B cells simultaneously bound the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells were efficiently reactivated by a 3rd dose of wild-type vaccine and correlated with the corresponding increase in neutralizing antibody titers. In contrast, pre-3rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit the added protection afforded by repeat short interval boosting. These data provide insight into the quantity and quality of mRNA-vaccine-induced immunity over time through 3 or more antigen exposures.
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Vacinas contra COVID-19 , COVID-19 , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Humanos , RNA Mensageiro , SARS-CoV-2 , Vacinas Sintéticas , Vacinas de mRNARESUMO
SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naive subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals.
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Linfócitos T CD8-Positivos/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/imunologia , SARS-CoV-2/fisiologia , Células Th1/imunologia , Vacina de mRNA-1273 contra 2019-nCoV , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Vacina BNT162 , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunização Secundária , Memória Imunológica , Lectinas Tipo C/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Adulto JovemRESUMO
Patients with B-cell lymphomas have altered cellular components of vaccine responses due to malignancy and therapy, and the optimal timing of vaccination relative to therapy remains unknown. Severe acute respiratory syndrome coronavirus 2 vaccines created an opportunity for new insights in vaccine timing because patients were challenged with a novel antigen across multiple phases of treatment. We studied serologic messenger RNA vaccine response in retrospective and prospective cohorts with lymphoma and chronic lymphocytic leukemia, paired with clinical and research immune parameters. Reduced serologic response was observed more frequently during active treatment, but nonresponse was also common within observation and posttreatment groups. Total immunoglobulin A and immunoglobulin M correlated with successful vaccine response. In individuals treated with anti-CD19-directed chimeric antigen receptor-modified T cells, nonresponse was associated with reduced B and T follicular helper cells. Predictors of vaccine response varied by disease and therapeutic group, and therefore further studies of immune health during and after cancer therapies are needed to individualize vaccine timing.
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Vacinas contra COVID-19 , COVID-19 , Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Estudos Retrospectivos , COVID-19/imunologia , COVID-19/prevenção & controle , Estudos Prospectivos , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinação , Imunoglobulina M/sangue , Linfoma/imunologia , Linfoma/terapia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Adverse childhood experiences (ACEs) are potentially traumatic exposures experienced during childhood, for example, neglect. There is growing evidence that the coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic conditions contributed to an increased risk of ACEs. As public health programs/services are re-evaluated and restored following the state of emergency, it is important to plan using an ACEs-informed lens. The aim of this study was to identify and prioritize initiatives or activities that Public Health Ontario (PHO) could undertake to support Ontario public health units' work towards ACEs-informed pandemic recovery plans. METHODS: The Child Health and Nutrition Research Initiative method was adapted to conduct a priority-setting exercise (May-October 2022). Two online surveys were administered with members of the Healthy Growth and Development (HGD) Evidence Network, comprised of public health unit staff working in child and family health/HGD from Ontario's 34 public health units. In the first survey, participants were asked to propose activities or initiatives that PHO could undertake to support Ontario public health units' work towards ACEs-informed planning. In the second survey, participants were asked to score the final list of options against pre-determined prioritization criteria (for example, relevance). Responses were numerically coded and used to calculate prioritization scores, which were used to rank the options. RESULTS: In all, 76% of public health units (n = 26) responded to the first survey to identify options. The 168 proposed ideas were consolidated into a final list of 13 options, which fall under PHO's scientific and technical support mandate areas (data and surveillance, evidence synthesis, collaboration and networking, knowledge exchange and research). A total of 79% of public health units (n = 27) responded to the follow-up survey to prioritize options. Prioritization scores ranged from 76.4% to 88.6%. The top-ranked option was the establishment of a new provincial ACEs community of practice. CONCLUSIONS: Over three quarters of public health units contributed to identifying and ranking 13 options for PHO to support public health units in considering and addressing ACEs through pandemic recovery planning. In consultation with the ACEs and Resilience Community of Practice, recently formed on the basis of this exercise, PHO will continue to use the ranked list of options to inform work-planning activities/priorities.
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Experiências Adversas da Infância , COVID-19 , Saúde Pública , Humanos , Ontário , COVID-19/epidemiologia , Criança , Prioridades em Saúde , Pandemias , Inquéritos e Questionários , SARS-CoV-2RESUMO
Changes in infant night waking during the first year of life are associated with individual (e.g., prematurity) and family (e.g., caregiver psychopathology) factors. This study examined the association between infant night waking and caregiver anxious-depressive symptoms during the first year of life in preterm and term infants. We considered between-person differences and within-person changes in caregiver anxious-depressive symptoms in relation to changes in infant night waking from 2- to 9-months. Racially (30.0% Black, 60.4% White, 9.5% multiracial/other) and socioeconomically (40.0% below median household income) diverse caregivers (N = 445) of full term (n = 258) and preterm (n = 187) infants were recruited from hospitals and clinics in two midwestern states. Caregivers completed measures of anxious-depression and their infant's night waking at four sampling periods (2-, 4-, 6-, and 9-months). Infant night wakings declined from 2- to 9-months. Between-person differences were observed, such that caregivers with higher average anxious-depressive symptoms or infants born full term reported more night wakings. Within-person effects of caregiver anxious-depressive symptoms were not significant. Caregiver anxious-depression is closely associated with infant night wakings. By considering a caregiver's average severity of anxious-depression, healthcare providers can more effectively plan infant sleep interventions. If caregiver anxious-depressive symptoms are ameliorated, night wakings may also decrease.
Los cambios en el despertar nocturno del infante durante el primer año de vida se asocian con factores individuales (v.g. nacimiento prematuro) y familiares (v.g. sicopatología de quien presta el cuidado). Este estudio examinó la asociación entre el despertar nocturno del infante y los síntomas de depresión por ansiedad de quien presta el cuidado durante el primer año de vida de infantes nacidos prematuramente y de ciclo completo. Tomamos en cuenta las diferencias entre las personas y los cambios dentro de las personas en los síntomas de depresión por ansiedad de quien presta el cuidado con relación a los cambios en el despertar nocturno del infante de los 2 a los 9 meses. Se reclutaron en hospitales y clínicas de dos estados del medio oeste cuidadores (N = 445) racial (30.0% de raza negra, 60.4% blancos, 9.5% multirraciales o de otra raza) y socioeconómicamente (40.0% por debajo del promedio de ingresos caseros) diversos, de infantes de ciclo completo (n = 258) y prematuros (n = 187). Los cuidadores completaron medidas de depresión por ansiedad y el despertar nocturno de sus infantes en cuatro períodos muestra (a los 2, 4, 6 y 9 meses). El despertar nocturno del infante declinó de los 2 a los 9 meses. Se observaron las diferencias entre personas, de tal manera que los cuidadores con un promedio mayor de síntomas de depresión por ansiedad o infantes nacidos en el ciclo completo reportaron más despertar nocturno. Los efectos de dentro de las personas de los síntomas de depresión por ansiedad del cuidador no fueron significativos. La depresión por ansiedad del cuidador se asocia cercanamente con el despertar nocturno del infante. Por medio de considerar el promedio de la severidad de la depresión por ansiedad del cuidador, quienes ofrecen el cuidado de salud pueden planear más eficazmente las intervenciones en cuanto al sueño del infante. Si se mejoran los síntomas de depresión por ansiedad de quien presta el cuidado, el despertar nocturno también podría disminuir.
Les changements dans le réveil nocturne du bébé pendant la première année sont liés à des facteurs individuels (par exemple la prématurité) et familiaux (par exemple la psychopathologie de la personne prenant soin de l'enfant). Cette étude a examiné le lien entre le réveil nocturne du bébé et les symptômes anxieux-dépressifs de la personne prenant soin de l'enfant durant la première année de vie de bébés prématurés et à terme. Nous avons considéré les différences entre les personnes et les changements au sein de la personne dans les symptômes anxieux-dépressifs de la personne prenant soin de l'enfant, en lien aux changements dans le réveil nocturne du bébé de 2 à 9 mois. Des personnes (N = 445) prenant soin d'un bébé à plein terme (n = 258) et prématuré (n = 187), divers du point de vue de leur race (30,0% noirs, 60,4% blancs, 9,5% multiracial/autre) et de leur statut socioéconomique (40,0% en dessous du revenu moyen d'une famille) ont été recrutés dans des hôpitaux et des cliniques des états au centre nord des Etats-Unis. Les personnes prenant soin du bébé ont rempli des mesures de dépression anxiété et de la nuit de leur bébé à quatre périodes de prélèvement des renseignements (2-, 4-, 6-, et 9- mois). Les réveils nocturnes du bébé ont décliné de 2- à 9- mois. Des différences entre les personnes ont été observées, au point que les personnes prenant soin du bébé avec la moyenne de symptômes anxieux-dépressifs la plus élevée ou des bébé nés à terme ont fait état de plus de réveils nocturnes. Les effets au sein de la personne des personnes prenant soin du bébé avec des symptômes anxieux-dépressifs n'étaient pas importants. La personne prenant du bébé avec une dépression anxieuse est fortement liée aux réveils nocturnes du bébé. En considérant la sévérité moyenne de la dépression anxieuse de la personne prenant soin du bébé, les prestataires de santé peuvent planifier les interventions concernant le sommeil du bébé de manière plus efficace. Si les symptômes anxieux-dépressifs de la personne prenant soin du bébé sont améliorer, alors les réveils nocturnes pourraient aussi diminuer.
Assuntos
Cuidadores , Depressão , Lactente , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Ansiedade , Pessoal de SaúdeRESUMO
BACKGROUND: Lesbian, gay, bisexual, and transgender (LGBT) cancer patients experience substantial health disparities, including poorer overall health and lower satisfaction with their cancer care than their heterosexual and cisgender counterparts, which may be due in part to a lack of culturally competent providers. To address these disparities, a web-based LGBT cultural competency training tailored to oncologists was developed by an interdisciplinary team of scientists, LGBT cancer survivors, cultural competency experts, oncologists, a web designer, and an instructional designer. METHODS: Oncologists (n = 44) were recruited from 3 academic cancer centers in Florida. Participants were administered the LGBT cultural competency training Curriculum for Oncologists on LGBT populations to Optimize Relevance and Skills (COLORS) and completed pre- and posttraining measures regarding LGBT-related knowledge, attitudes (including general negative attitudes and health care-related attitudes), and clinical practices. After the training, participants completed training acceptability measures. RESULTS: Of the 44 participants, 33 (75%) completed the COLORS training. Participants were 55% non-Hispanic white, 63% male, and had a mean age of 47 years. Participants demonstrated significant improvements in LGBT-related knowledge (t = -4.9, P < .001), attitudes (Z = -3.0, P = .002; t = -2.5, P = .019), and clinical practices (Z = -3.5, P < .001) after completing the COLORS training (Wilcoxon signed rank tests were used for nonnormally distributed variables). Moreover, training acceptability was high, with 82% of participants rating the training as high quality, and 97% being willing to recommend the training to a colleague. CONCLUSION: The COLORS training is both feasible to administer and acceptable for use with oncologists, and may improve oncologists' LGBT-related knowledge, attitudes, and clinical practices. Larger trials are needed to examine the training's effectiveness in reducing LGBT cancer disparities, as well as its applicability to other types of care providers.
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Atitude do Pessoal de Saúde , Competência Cultural/educação , Oncologistas/educação , Comportamento Sexual/psicologia , Bissexualidade/psicologia , Competência Cultural/psicologia , Feminino , Florida/epidemiologia , Homossexualidade Feminina/psicologia , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Oncologistas/psicologia , Minorias Sexuais e de Gênero/psicologia , Pessoas Transgênero/psicologiaRESUMO
BACKGROUND: The symbiotic interactions that occur between humans and organisms in our environment have a tremendous impact on our health. Recently, there has been a surge in interest in understanding the complex relationships between the microbiome and human health and host immunity against microbial pathogens, among other things. To collect and manage data about these interactions and their complexity, scientists will need ontologies that represent symbiotic interactions as they occur in reality. METHODS: We began with two papers that reviewed the usage of 'symbiosis' and related terms in the biology and ecology literature and prominent textbooks. We then analyzed several prominent standard terminologies and ontologies that contain representations of symbiotic interactions, to determine if they appropriately defined 'symbiosis' and related terms according to current scientific usage as identified by the review papers. In the process, we identified several subtypes of symbiotic interactions, as well as the characteristics that differentiate them, which we used to propose textual and axiomatic definitions for each subtype of interaction. To both illustrate how to use the ontological representations and definitions we created and provide additional quality assurance on key definitions, we carried out a referent tracking analysis and representation of three scenarios involving symbiotic interactions among organisms. RESULTS: We found one definition of 'symbiosis' in an existing ontology that was consistent with the vast preponderance of scientific usage in biology and ecology. However, that ontology changed its definition during the course of our work, and discussions are ongoing. We present a new definition that we have proposed. We also define 34 subtypes of symbiosis. Our referent tracking analysis showed that it is necessary to define symbiotic interactions at the level of the individual, rather than at the species level, due to the complex nature in which organisms can go from participating in one type of symbiosis with one organism to participating in another type of symbiosis with a different organism. CONCLUSION: As a result of our efforts here, we have developed a robust representation of symbiotic interactions using a realism-based approach, which fills a gap in existing biomedical ontologies.
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Ontologias Biológicas , Simbiose , HumanosAssuntos
Serviços de Saúde da Criança/organização & administração , Vacinação em Massa/organização & administração , Ambulatório Hospitalar/organização & administração , Adulto , Criança , Serviços de Saúde da Criança/estatística & dados numéricos , Pré-Escolar , Estudos de Viabilidade , Humanos , Lactente , Recém-Nascido , Vacinação em Massa/estatística & dados numéricos , Projetos Piloto , QueenslandRESUMO
Objective: Rates of postpartum depression (PPD) increased during the COVID-19 pandemic, further highlighting the need for effective, accessible treatments for PPD. While public health nurses (PHNs) can be trained to help treat PPD, it is not known if they can effectively deliver evidence-based psychotherapies online to those with PPD.Methods: Mothers (n = 159) living in Ontario, Canada, with an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 10 and an infant < 12 months of age were randomized to receive a 9-week group cognitive behavioral therapy (CBT) intervention delivered by PHNs over Zoom, between October 2020 and November 2021. Experimental group participants received CBT plus treatment as usual (TAU), and control participants received TAU alone. Participants were assessed at baseline (T1), 9 weeks later (T2), and 6 months after T2 (T3). Primary outcomes were changes in EPDS score and current major depressive disorder (MDD) as measured by the Mini International Neuropsychiatric Interview. Secondary outcomes included worry, social support, the mother-infant relationship, and infant temperament.Results: At T2, experimental group participants showed clinically and statistically significant reductions on the EPDS (d = 0.65) and decreases in postpartum worry (d = 0.38) and rejection and pathological anger toward their infant (d = 0.44). They were also less likely to meet diagnostic criteria for current MDD compared to control participants (OR = 5.09; 95% CI, 1.18-21.98; number needed to treat [NNT: 3.7]). These improvements remained stable 6 months later (T3).Conclusions: PHNs can be trained to deliver effective online group CBT for PPD to reduce depression and worry and improve aspects of the mother-infant relationship, and they represent an important way to increase access to effective treatment for PPD.Trial Registration: ClinicalTrials.gov identifier: NCT04928742.
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COVID-19 , Terapia Cognitivo-Comportamental , Depressão Pós-Parto , Transtorno Depressivo Maior , Enfermeiros de Saúde Pública , Feminino , Lactente , Humanos , Depressão Pós-Parto/terapia , Depressão Pós-Parto/diagnóstico , Transtorno Depressivo Maior/terapia , PandemiasRESUMO
The translational research community, in general, and the Clinical and Translational Science Awards (CTSA) community, in particular, share the vision of repurposing EHRs for research that will improve the quality of clinical practice. Many members of these communities are also aware that electronic health records (EHRs) suffer limitations of data becoming poorly structured, biased, and unusable out of original context. This creates obstacles to the continuity of care, utility, quality improvement, and translational research. Analogous limitations to sharing objective data in other areas of the natural sciences have been successfully overcome by developing and using common ontologies. This White Paper presents the authors' rationale for the use of ontologies with computable semantics for the improvement of clinical data quality and EHR usability formulated for researchers with a stake in clinical and translational science and who are advocates for the use of information technology in medicine but at the same time are concerned by current major shortfalls. This White Paper outlines pitfalls, opportunities, and solutions and recommends increased investment in research and development of ontologies with computable semantics for a new generation of EHRs.
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Despite a clear role in protective immunity, the durability and quality of antibody and memory B cell responses induced by mRNA vaccination, particularly by a 3 rd dose of vaccine, remains unclear. Here, we examined antibody and memory B cell responses in a cohort of individuals sampled longitudinally for â¼9-10 months after the primary 2-dose mRNA vaccine series, as well as for â¼3 months after a 3 rd mRNA vaccine dose. Notably, antibody decay slowed significantly between 6- and 9-months post-primary vaccination, essentially stabilizing at the time of the 3 rd dose. Antibody quality also continued to improve for at least 9 months after primary 2-dose vaccination. Spike- and RBD-specific memory B cells were stable through 9 months post-vaccination with no evidence of decline over time, and â¼40-50% of RBD-specific memory B cells were capable of simultaneously recognizing the Alpha, Beta, Delta, and Omicron variants. Omicron-binding memory B cells induced by the first 2 doses of mRNA vaccine were boosted significantly by a 3rd dose and the magnitude of this boosting was similar to memory B cells specific for other variants. Pre-3 rd dose memory B cell frequencies correlated with the increase in neutralizing antibody titers after the 3 rd dose. In contrast, pre-3 rd dose antibody titers inversely correlated with the fold-change of antibody boosting, suggesting that high levels of circulating antibodies may limit reactivation of immunological memory and constrain further antibody boosting by mRNA vaccines. These data provide a deeper understanding of how the quantity and quality of antibody and memory B cell responses change over time and number of antigen exposures. These data also provide insight into potential immune dynamics following recall responses to additional vaccine doses or post-vaccination infections.
RESUMO
Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting.
Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Vacinas contra COVID-19 , COVID-19/imunologia , SARS-CoV-2/imunologia , Vacinas Sintéticas , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinação , Adulto Jovem , Vacinas de mRNARESUMO
Novel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naïve subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naïve subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naïve and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naïve individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naïve individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.
RESUMO
SARS-CoV-2 mRNA vaccines have shown remarkable efficacy, especially in preventing severe illness and hospitalization. However, the emergence of several variants of concern and reports of declining antibody levels have raised uncertainty about the durability of immune memory following vaccination. In this study, we longitudinally profiled both antibody and cellular immune responses in SARS-CoV-2 naïve and recovered individuals from pre-vaccine baseline to 6 months post-mRNA vaccination. Antibody and neutralizing titers decayed from peak levels but remained detectable in all subjects at 6 months post-vaccination. Functional memory B cell responses, including those specific for the receptor binding domain (RBD) of the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) variants, were also efficiently generated by mRNA vaccination and continued to increase in frequency between 3 and 6 months post-vaccination. Notably, most memory B cells induced by mRNA vaccines were capable of cross-binding variants of concern, and B cell receptor sequencing revealed significantly more hypermutation in these RBD variant-binding clones compared to clones that exclusively bound wild-type RBD. Moreover, the percent of variant cross-binding memory B cells was higher in vaccinees than individuals who recovered from mild COVID-19. mRNA vaccination also generated antigen-specific CD8+ T cells and durable memory CD4+ T cells in most individuals, with early CD4+ T cell responses correlating with humoral immunity at later timepoints. These findings demonstrate robust, multi-component humoral and cellular immune memory to SARS-CoV-2 and current variants of concern for at least 6 months after mRNA vaccination. Finally, we observed that boosting of pre-existing immunity with mRNA vaccination in SARS-CoV-2 recovered individuals primarily increased antibody responses in the short-term without significantly altering antibody decay rates or long-term B and T cell memory. Together, this study provides insights into the generation and evolution of vaccine-induced immunity to SARS-CoV-2, including variants of concern, and has implications for future booster strategies.
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The durability of immune memory after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination remains unclear. In this study, we longitudinally profiled vaccine responses in SARS-CoV-2naïve and recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. By contrast, mRNA vaccines generated functional memory B cells that increased from 3 to 6 months postvaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity. Recall responses to vaccination in individuals with preexisting immunity primarily increased antibody levels without substantially altering antibody decay rates. Together, these findings demonstrate robust cellular immune memory to SARS-CoV-2 and its variants for at least 6 months after mRNA vaccination.
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Vacinas contra COVID-19/imunologia , Memória Imunológica , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Vacinas de mRNA/imunologia , HumanosRESUMO
Sm proteins form stable ribonucleoprotein (RNP) complexes with small nuclear (sn)RNAs and are core components of the eukaryotic spliceosome. In vivo, the assembly of Sm proteins onto snRNAs requires the survival motor neurons (SMN) complex. Several reports have shown that SMN protein binds with high affinity to symmetric dimethylarginine (sDMA) residues present on the C-terminal tails of SmB, SmD1, and SmD3. This post-translational modification is thought to play a crucial role in snRNP assembly. In human cells, two distinct protein arginine methyltransferases (PRMT5 and PRMT7) are required for snRNP biogenesis. However, in Drosophila, loss of Dart5 (the fruit fly PRMT5 ortholog) has little effect on snRNP assembly, and homozygous mutants are completely viable. To resolve these apparent differences, we examined this topic in detail and found that Drosophila Sm proteins are also methylated by two methyltransferases, Dart5/PRMT5 and Dart7/PRMT7. Unlike dart5, we found that dart7 is an essential gene. However, the lethality associated with loss of Dart7 protein is apparently unrelated to defects in snRNP assembly. To conclusively test the requirement for sDMA modification of Sm proteins in Drosophila snRNP assembly, we constructed a fly strain that exclusively expresses an isoform of SmD1 that cannot be sDMA modified. Interestingly, these flies were viable, and snRNP assays revealed no defects in comparison to wild type. In contrast, dart5 mutants displayed a strong synthetic lethal phenotype in the presence of a hypomorphic Smn mutation. We therefore conclude that dart5 is required for viability when SMN is limiting.
Assuntos
Proteínas de Drosophila/biossíntese , Drosophila melanogaster/metabolismo , Ribonucleoproteínas Nucleares Pequenas/biossíntese , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Autoantígenos/química , Autoantígenos/genética , Autoantígenos/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Genes de Insetos , Humanos , Metilação , Metiltransferases/genética , Metiltransferases/metabolismo , Dados de Sequência Molecular , Mutação , Proteínas Metiltransferases/genética , Proteínas Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Proteína-Arginina N-Metiltransferases/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribonucleoproteínas Nucleares Pequenas/química , Ribonucleoproteínas Nucleares Pequenas/genética , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Especificidade da Espécie , Proteínas Centrais de snRNPRESUMO
INTRODUCTION: The pediatric primary care office is an ideal setting to address children's socioemotional-behavioral health. However, research is limited regarding parents' experiences and satisfaction in sharing mental-health concerns about their children during well-child visits. METHOD: One thousand seven hundred sixty-three parents and caregivers with children aged 3-17 years completed an online survey that addressed mental-health-related communication. RESULTS: Findings supported the key role that primary care providers play in communicating about mental-health issues; 75% of parents who had such a concern about their child raised it during the visit, although the majority desired more time devoted to discussing mental health. Parents' comfort discussing mental-health concerns was inversely related to providers' dismissing those concerns. DISCUSSION: Despite satisfaction with how providers addressed mental-health issues, results suggested that nonjudgmental, knowledgeable staff and discussion of child and parent strengths could facilitate both parental comfort and communication between parents and pediatricians.
Assuntos
Comunicação em Saúde , Saúde Mental , Pais , Relações Médico-Paciente , Criança , Humanos , Atenção Primária à SaúdeRESUMO
OBJECTIVE: Despite substantial LGBT cancer health disparities, there are no LGBT cultural competency trainings tailored for oncologists. Here we describe the systematic development of a web-based, oncology-focused LGBT cultural competency training. METHODS: A literature review regarding LGBT cancer outcomes and competency training was conducted to identify potential training content. An expert panel meeting, including LGBT cancer survivors, cultural competency experts, oncologists, a web designer, and an instructional designer, was held to solidify the training content focus. Following the panel, the training was developed in collaboration with an instructional designer, a web designer, and LGBT community members. RESULTS: The training modules include: 1) LGBT Basics; 2) Inclusive Environments; 3) Initiating Oncology Care with LGBT Patients; and 4) Issues in Cancer Survivorship among LGBT Patients. Module content is interactive, and models effective communication. CONCLUSION: The process of collaboration with a diverse group of stakeholders and three cancer centers in Florida has resulted in a practical and efficient web-based resource for LGBT cultural competency training for oncologists. PRACTICE IMPLICATIONS: Feedback from stakeholders indicates that training in this area is needed and will be well-received by oncologists. We are currently conducting an evaluation of this training among oncologists and LGBT community members.
Assuntos
Competência Clínica , Competência Cultural/educação , Capacitação em Serviço/métodos , Internet , Oncologistas/educação , Currículo , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Oncologia/educação , Melhoria de Qualidade , Minorias Sexuais e de Gênero , Pessoas TransgêneroRESUMO
Obesity has been linked to several types of cancer. Access to adequate health information activates people's participation in managing their own health, which ultimately improves their health outcomes. Nevertheless, the existing online information about the relationship between obesity and cancer is heterogeneous and poorly organized. A formal knowledge representation can help better organize and deliver quality health information. Currently, there are several efforts in the biomedical domain to convert unstructured data to structured data and store them in Semantic Web knowledge bases (KB). In this demo paper, we present, OC-2-KB (Obesity and Cancer to Knowledge Base), a system that is tailored to guide the automatic KB construction for managing obesity and cancer knowledge from free-text scientific literature (i.e., PubMed abstracts) in a systematic way. OC-2-KB has two important modules which perform the acquisition of entities and the extraction then classification of relationships among these entities. We tested the OC-2-KB system on a data set with 23 manually annotated obesity and cancer PubMed abstracts and created a preliminary KB with 765 triples. We conducted a preliminary evaluation on this sample of triples and reported our evaluation results.