A Recombinant Rhesus Monkey Rhadinovirus Deleted of Glycoprotein L Establishes Persistent Infection of Rhesus Macaques and Elicits Conventional T Cell Responses.

A replication-competent, recombinant strain of rhesus monkey rhadinovirus (RRV) expressing the Gag protein of SIVmac239 was constructed in the context of a glycoprotein L (gL) deletion mutation. Deletion of gL detargets the virus from Eph family receptors. The ability of this gL-minus Gag recombinant RRV to infect, persist, and elicit immune responses was evaluated after intravenous inoculation of two Mamu-A*01+ RRV-naive rhesus monkeys. Both monkeys responded with an anti-RRV antibody response, and quantitation of RRV DNA in peripheral blood mononuclear cells (PBMC) by real-time PCR revealed levels similar to those in monkeys infected with recombinant gL+ RRV. Comparison of RRV DNA levels in sorted CD3+ versus CD20+ versus CD14+ PBMC subpopulations indicated infection of the CD20+ subpopulation by the gL-minus RRV. This contrasts with results obtained with transformed B cell lines in vitro, in which deletion of gL resulted in markedly reduced infectivity. Over a period of 20 weeks, Gag-specific CD8+ T cell responses were documented by major histocompatibility complex class I (MHC-I) tetramer staining. Vaccine-induced CD8+ T cell responses, which were predominantly directed against the Mamu-A*01-restricted Gag181-189CM9 epitope, could be inhibited by blockade of MHC-I presentation. Our results indicate that gL and the interaction with Eph family receptors are dispensable for the colonization of the B cell compartment following high-dose infection by the intravenous route, which suggests the existence of alternative receptors. Further, gL-minus RRV elicits cellular immune responses that are predominantly canonical in nature.IMPORTANCE Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with a substantial disease burden in sub-Saharan Africa, often in the context of human immunodeficiency virus (HIV) infection. The related rhesus monkey rhadinovirus (RRV) has shown potential as a vector to immunize monkeys with antigens from simian immunodeficiency virus (SIV), the macaque model for HIV. KSHV and RRV engage cellular receptors from the Eph family via the viral gH/gL glycoprotein complex. We have now generated a recombinant RRV that expresses the SIV Gag antigen and does not express gL. This recombinant RRV was infectious by the intravenous route, established persistent infection in the B cell compartment, and elicited strong immune responses to the SIV Gag antigen. These results argue against a role for gL and Eph family receptors in B cell infection by RRV in vivo and have implications for the development of a live-attenuated KSHV vaccine or vaccine vector.

The Frequency of Vaccine-Induced T-Cell Responses Does Not Predict the Rate of Acquisition after Repeated Intrarectal SIVmac239 Challenges in Mamu-B*08+ Rhesus Macaques.

Approximately 50% of rhesus macaques (RMs) expressing the major histocompatibility complex class I (MHC-I) allele Mamu-B*08 spontaneously control chronic-phase viremia after infection with the pathogenic simian immunodeficiency virus mac239 (SIVmac239) clone. CD8+ T-cell responses in these animals are focused on immunodominant Mamu-B*08-restricted SIV epitopes in Vif and Nef, and prophylactic vaccination with these epitopes increases the incidence of elite control in SIVmac239-infected Mamu-B*08-positive (Mamu-B*08+ ) RMs. Here we evaluated if robust vaccine-elicited CD8+ T-cell responses against Vif and Nef can prevent systemic infection in Mamu-B*08+ RMs following mucosal SIV challenges. Ten Mamu-B*08+ RMs were vaccinated with a heterologous prime/boost/boost regimen encoding Vif and Nef, while six sham-vaccinated MHC-I-matched RMs served as the controls for this experiment. Vaccine-induced CD8+ T cells against Mamu-B*08-restricted SIV epitopes reached high frequencies in blood but were present at lower levels in lymph node and gut biopsy specimens. Following repeated intrarectal challenges with SIVmac239, all control RMs became infected by the sixth SIV exposure. By comparison, four vaccinees were still uninfected after six challenges, and three of them remained aviremic after 3 or 4 additional challenges. The rate of SIV acquisition in the vaccinees was numerically lower (albeit not statistically significantly) than that in the controls. However, peak viremia was significantly reduced in infected vaccinees compared to control animals. We found no T-cell markers that distinguished vaccinees that acquired SIV infection from those that did not. Additional studies will be needed to validate these findings and determine if cellular immunity can be harnessed to prevent the establishment of productive immunodeficiency virus infection.IMPORTANCE It is generally accepted that the antiviral effects of vaccine-induced classical CD8+ T-cell responses against human immunodeficiency virus (HIV) are limited to partial reductions in viremia after the establishment of productive infection. Here we show that rhesus macaques (RMs) vaccinated with Vif and Nef acquired simian immunodeficiency virus (SIV) infection at a lower (albeit not statistically significant) rate than control RMs following repeated intrarectal challenges with a pathogenic SIV clone. All animals in the present experiment expressed the elite control-associated major histocompatibility complex class I (MHC-I) molecule Mamu-B*08 that binds immunodominant epitopes in Vif and Nef. Though preliminary, these results provide tantalizing evidence that the protective efficacy of vaccine-elicited CD8+ T cells may be greater than previously thought. Future studies should examine if vaccine-induced cellular immunity can prevent systemic viral replication in RMs that do not express MHC-I alleles associated with elite control of SIV infection.

Mamu-B*17+ Rhesus Macaques Vaccinated with env, vif, and nef Manifest Early Control of SIVmac239 Replication.

Certain major histocompatibility complex class I (MHC-I) alleles are associated with spontaneous control of viral replication in human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)-infected rhesus macaques (RMs). These cases of "elite" control of HIV/SIV replication are often immune-mediated, thereby providing a framework for studying anti-lentiviral immunity. In this study, we examined how vaccination impacts SIV replication in RMs expressing the MHC-I allele Mamu-B*17 Approximately 21% of Mamu-B*17+ and 50% of Mamu-B*08+ RMs control chronic-phase viremia after SIVmac239 infection. Because CD8+ T cells targeting Mamu-B*08-restricted SIV epitopes have been implicated in virologic suppression in Mamu-B*08+ RMs, we investigated whether this might also be true for Mamu-B*17+ RMs. Two groups of Mamu-B*17+ RMs were vaccinated with genes encoding Mamu-B*17-restricted epitopes in Vif and Nef. These genes were delivered by themselves (group 1) or together with env (group 2). Group 3 included MHC-I-matched RMs and served as the control group. Surprisingly, the group 1 vaccine regimen had little effect on viral replication compared to group 3, suggesting that unlike Mamu-B*08+ RMs, preexisting SIV-specific CD8+ T cells alone do not facilitate long-term virologic suppression in Mamu-B*17+ RMs. Remarkably, however, 5/8 group 2 vaccinees controlled viremia to <15 viral RNA copies/ml soon after infection. No serological neutralizing activity against SIVmac239 was detected in group 2, although vaccine-elicited gp140-binding antibodies correlated inversely with nadir viral loads. Collectively, these data shed new light on the unique mechanism of elite control in Mamu-B*17+ RMs and implicate vaccine-induced, nonneutralizing anti-Env antibodies in the containment of immunodeficiency virus infection.IMPORTANCE A better understanding of the immune correlates of protection against HIV might facilitate the development of a prophylactic vaccine. Therefore, we investigated simian immunodeficiency virus (SIV) infection outcomes in rhesus macaques expressing the major histocompatibility complex class I allele Mamu-B*17 Approximately 21% of Mamu-B*17+ macaques spontaneously controlled chronic phase viremia after SIV infection, an effect that may involve CD8+ T cells targeting Mamu-B*17-restricted SIV epitopes. We vaccinated Mamu-B*17+ macaques with genes encoding immunodominant epitopes in Vif and Nef alone (group 1) or together with env (group 2). Although neither vaccine regimen prevented SIV infection, 5/8 group 2 vaccinees controlled viremia to below detection limits shortly after infection. This outcome, which was not observed in group 1, was associated with vaccine-induced, nonneutralizing Env-binding antibodies. Together, these findings suggest a limited contribution of Vif- and Nef-specific CD8+ T cells for virologic control in Mamu-B*17+ macaques and implicate anti-Env antibodies in containment of SIV infection.

Vaccine-induced immune responses against both Gag and Env improve control of simian immunodeficiency virus replication in rectally challenged rhesus macaques.

The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4). Following repeated intrarectal challenges with a marginal dose of the neutralization-resistant SIVmac239 clone, vaccinees in Groups 1-3 became infected at similar rates compared to control animals. Unexpectedly, vaccinees in Group 4 became infected at a slower pace than the other animals, although this difference was not statistically significant. Group 1 exhibited the best post-acquisition virologic control of SIV infection, with significant reductions in both peak and chronic phase viremia. Indeed, 5/8 Group 1 vaccinees had viral loads of less than 2,000 vRNA copies/mL of plasma in the chronic phase. Vaccine regimens that did not contain gag (Group 2), env (Group 3), or both of these inserts (Group 4) were largely ineffective at decreasing viremia. Thus, vaccine-induced immune responses against both Gag and Env appeared to maximize control of immunodeficiency virus replication. Collectively, these findings are relevant for HIV-1 vaccine design as they provide additional insights into which of the lentiviral proteins might serve as the best vaccine immunogens.

Use of a Recombinant Gamma-2 Herpesvirus Vaccine Vector against Dengue Virus in Rhesus Monkeys.

Research on vaccine approaches that can provide long-term protection against dengue virus infection is needed. Here we describe the construction, immunogenicity, and preliminary information on the protective capacity of recombinant, replication-competent rhesus monkey rhadinovirus (RRV), a persisting herpesvirus. One RRV construct expressed nonstructural protein 5 (NS5), while a second recombinant expressed a soluble variant of the E protein (E85) of dengue virus 2 (DENV2). Four rhesus macaques received a single vaccination with a mixture of both recombinant RRVs and were subsequently challenged 19 weeks later with 1 × 105 PFU of DENV2. During the vaccine phase, plasma of all vaccinated monkeys showed neutralizing activity against DENV2. Cellular immune responses against NS5 were also elicited, as evidenced by major histocompatibility complex class I (MHC-I) tetramer staining in the one vaccinated monkey that was Mamu-A*01 positive. Unlike two of two unvaccinated controls, two of the four vaccinated monkeys showed no detectable viral RNA sequences in plasma after challenge. One of these two monkeys also showed no anamnestic increases in antibody levels following challenge and thus appeared to be protected against the acquisition of DENV2 following high-dose challenge. Continued study will be needed to evaluate the performance of herpesviral and other persisting vectors for achieving long-term protection against dengue virus infection.IMPORTANCE Continuing studies of vaccine approaches against dengue virus (DENV) infection are warranted, particularly ones that may provide long-term immunity against all four serotypes. Here we investigated whether recombinant rhesus monkey rhadinovirus (RRV) could be used as a vaccine against DENV2 infection in rhesus monkeys. Upon vaccination, all animals generated antibodies capable of neutralizing DENV2. Two of four vaccinated monkeys showed no detectable viral RNA after subsequent high-dose DENV2 challenge at 19 weeks postvaccination. Furthermore, one of these vaccinated monkeys appeared to be protected against the acquisition of DENV2 infection on the basis of undetectable viral loads and the lack of an anamnestic antibody response. These findings underscore the potential utility of recombinant herpesviruses as vaccine vectors.

Potent Plasmablast-Derived Antibodies Elicited by the National Institutes of Health Dengue Vaccine.

Exposure to dengue virus (DENV) is thought to elicit lifelong immunity, mediated by DENV-neutralizing antibodies (nAbs). However, Abs generated by primary infections confer serotype-specific protection, and immunity against other serotypes develops only after subsequent infections. Accordingly, the induction of these nAb responses acquired after serial DENV infections has been a long-sought-after goal for vaccination. Nonetheless, it is still unclear if tetravalent vaccines can elicit or recall nAbs. In this study, we have characterized the responses from a volunteer who had been previously exposed to DENV and was immunized with the live attenuated tetravalent vaccine Butantan-DV, developed by the NIH and Butantan Institute. Eleven days after vaccination, we observed an ∼70-fold expansion of the plasmablast population. We generated 21 monoclonal Abs (MAbs) from singly sorted plasmablasts. These MAbs were the result of clonal expansions and had significant levels of somatic hypermutation (SHM). Nineteen MAbs (90.5%) neutralized at least one DENV serotype at concentrations of 1 µg/ml or less; 6 of the 21 MAbs neutralized three or more serotypes. Despite the tetravalent composition of the vaccine, we observed a neutralization bias in the induced repertoire: DENV3 was targeted by 18 of the 19 neutralizing MAbs (nMAbs). Furthermore, the P3D05 nMAb neutralized DENV3 with extraordinary potency (concentration to achieve half-maximal neutralization [Neut50] = 0.03 µg/ml). Thus, the Butantan-DV vaccine engendered a mature, antigen-selected B cell repertoire. Our results suggest that preexisting responses elicited by a previous DENV3 infection were recalled by immunization.IMPORTANCE The dengue epidemic presents a global public health challenge that causes widespread economic burden and remains largely unchecked by existing control strategies. Successful control of the dengue epidemic will require effective prophylactic and therapeutic interventions. Several vaccine clinical efficacy trials are approaching completion, and the chances that one or more live attenuated tetravalent vaccines (LATVs) will be introduced worldwide is higher than ever. While it is widely accepted that dengue virus (DENV)-neutralizing antibody (nAb) titers are associated with protection, the Ab repertoire induced by LATVs remain uncharacterized. Here, we describe the isolation of potent (Neut50 < 0.1 µg/ml) nAbs from a DENV-seropositive volunteer immunized with the tetravalent vaccine Butantan-DV, which is currently in phase III trials.

Dengue Virus Evades AAV-Mediated Neutralizing Antibody Prophylaxis in Rhesus Monkeys.

Development of vaccines against mosquito-borne Flaviviruses is complicated by the occurrence of antibody-dependent enhancement (ADE), which can increase disease severity. Long-term delivery of neutralizing antibodies (nAbs) has the potential to effectively block infection and represents an alternative to vaccination. The risk of ADE may be avoided by using prophylactic nAbs harboring amino acid mutations L234A and L235A (LALA) in the immunoglobulin G (IgG) constant region. Here, we used recombinant adeno-associated viruses (rAAVs) to deliver the anti-dengue virus 3 (DENV3) nAb P3D05. While the administration of rAAV-P3D05-rhesus immunoglobulin G1 (rhIgG1)-LALA to rhesus macaques engendered DENV3-neutralizing activity in serum, it did not prevent infection. The emergence of viremia following DENV3 challenge was delayed by 3-6 days in the rAAV-treated group, and replicating virus contained the envelope mutation K64R. This neutralization-resistant variant was also confirmed by virus outgrowth experiments in vitro. By delivering P3D05 with unmutated Fc sequences, we further demonstrated that DENV3 also evaded wild-type nAb prophylaxis, and serum viral loads appeared to be higher in the presence of low levels of unmutated P3D05-rhIgG1. Our study shows that a vectored approach for long-term delivery of nAbs with the LALA mutations is promising, but prophylaxis using a single nAb is likely insufficient at preventing DENV infection and replication.

Telesimulation about home visits and child care: facilitators, barriers and perception of Nursing students.

OBJECTIVE: to evaluate the facilitators, barriers and perceptions of Nursing students in learning about home visiting and child care through Telesimulation during the COVID-19 pandemic. METHOD: a qualitative study to evaluate Telesimulation via computers, grounded on Kolb's theoretical model. A semi-structured questionnaire and the Student Satisfaction and Self-Confidence in Learning Scale were applied, with descriptive analysis and qualitative thematic analysis on the perceptions of 41 Nursing students. RESULTS: the contextualized Telesimulation provided learning opportunities in dimensions of the pedagogical strategy, telesimulated scenario, communication and specificities of child care in home visits. It was considered a safe and dynamic activity that helped knowledge consolidation and reflective attitudes, proximity to reality, and develop interaction, observation and types of approaches. There were restrictions due to Internet connection failures. A large percentage of the students indicated good satisfaction and self-confidence level with learning in the scale applied. CONCLUSION: the real clinical situation with remote immersion allowed observation, decision-making, reflection and elaboration of conclusions, inherent to the experiential learning cycle. The set of elements of this Telesimulation created an environment that stimulated the interest of Nursing students for other learning stages, suggesting a space that strengthens knowledge and maintains dialogue with face-to-face practices.

Prebriefing in clinical simulation in nursing: scoping review.

OBJECTIVE: To map the concept and structural elements of the prebriefing phase in clinical simulations in nursing. METHOD: Scoping review with searches between May and June 2021 in the databases PubMed, Virtual Health Library, EMBASE, CINAHL, SCOPUS, Web of Science, CAPES Catalog of Theses and Dissertations, Brazilian Digital Library of Theses and Dissertations and Google Scholar, in portuguese, spanish and english, without time limit. RESULTS: 24 studies were selected. In 17 articles (70.8%) the authors used the spelling prebriefing (in italics and amended), to refer to the stage that precedes the simulation, including preparatory activities and guidance. Alternative methods for prebriefing were described (reflective practices, laboratories, games and videos). CONCLUSION: There is no consensus regarding the concept and elements that constitute the prebriefing. This simulation stage contributes to participant satisfaction, participation and psychological safety, with better learning outcomes.

Interdisciplinary simulation scenario in nursing education: Humanized childbirth and birth.

OBJECTIVE: to develop and validate with a panel of experts a scenario of maternal-child clinical simulation, related to humanized childbirth and birth. METHOD: methodological study based on the Jeffries framework and standardized guides of the International Nursing Association for Clinical Simulation in Learning, which used analysis with descriptive statistics for general aspects of adherence to the aforementioned guide and inferential statistics for validating the checklist of actions through the Intraclass Correlation Coefficient (ICC). RESULTS: the scenario contains learning objectives, necessary resources, prebriefing and debriefing of guidelines, description of the simulated situation, participants and roles, and checklist of expected actions. The validation obtained an agreement level above 80% in all aspects evaluated by 31 experts, highlighting realism of the environment and setting, vital sign parameters, alignment with scientific literature and encouragement of critical thinking and problem solving. In addition, the checklist of actions was validated with 0.899 agreement among experts, statistically analyzed by the ICC and Cronbach's alpha 0.908 (95% confidence interval). CONCLUSION: the simulated scenario on humanized childbirth and birth can strengthen the articulation between women's and children's health disciplines, and was validated by experts.

Serious games as an educational strategy to control childhood obesity: a systematic literature review1.

OBJECTIVES: to identify in the literature the efficacy of serious games to improve knowledge for and/or behavioral changes among overweight or obese children. METHOD: Systematic Literature Review. The Cochrane Systematic Reviews Handbook was used. The studies were collected from the following databases: Public Medline; Web Of Science; Science Direct; Latin American and Caribbean Health Sciences Literature; and the Health Game Research and Cumulative Index to Nursing & Allied Health Literature. The descriptors were video games and obesity, while the key word was serious games. Inclusion criteria were: studies classified as Randomized Clinical Trials written in English, Spanish or Portuguese and in which children were the subjects of the study. RESULTS: 2,722 studies were identified in the initial search and six studies remained in the final sample. The papers focused on encouraging behavioral changes in players, including physical exercise and improved eating habits. The studies report that serious games are a potential strategy to encourage positive coping with childhood obesity. CONCLUSION: research in this field is an expanding and promising strategy and serious games represent an alternative means to provide health education to children.

Desenvolvimento e avaliação de infográfico animado: medicação segura em saúde da criança / Development and assessment of animated infographic: safe medication for children's health

Resumo Objetivo Desenvolver e avaliar um infográfico animado como recurso didático para o ensino de medicação segura em saúde da criança. Métodos Trata-se de estudo metodológico composto pela criação de um infográfico animado sobre medicação segura em saúde da criança para estudantes do ensino superior de enfermagem. O desenvolvimento desta tecnologia digital educacional seguiu quatro etapas: planejamento, produção, implementação e avaliação. O critério para avaliação foi concordância superior a 90%, analisada por meio do Índice de Validade de Conteúdo.Resultados: A versão final do infográfico animado possui 37 telas, as quais apresentam as metas do 3º Desafio da Organização Mundial de Saúde, os eventos adversos, fatores de risco do público-alvo e, por fim, as recomendações sobre boas práticas na administração segura de medicamentos em saúde da criança. O infográfico foi avaliado por 13 especialistas e obteve-se concordância entre todos os itens superior a 90%. Conclusão O infográfico animado foi considerado um recurso educacional válido, que poderá favorecer o processo de ensino aprendizagem de estudantes de enfermagem no que tange à conduta de boas práticas na administração de medicação na área da saúde da criança.

Resumen Objetivo Desarrollar y evaluar un infográfico animado como recurso didáctico para la enseñanza de medicación segura para la salud de los niños. Métodos Se trata de estudio metodológico compuesto por la creación de un infográfico animado sobre medicación segura para la salud del niño para estudiantes de la enseñanza superior en enfermería. El desarrollo de esta tecnología digital educativa siguió cuatro etapas: planificación, producción, implementación y evaluación. El criterio para la evaluación fue la coincidencia superior al 90 %, analizada por medio del Índice de Validez de Contenido.Resultados: La versión final del infográfico animado cuenta con 37 pantallas que presentan las metas del 3er Desafío de la Organización Mundial de Salud, los eventos adversos, factores de riesgo del público destinatario y, por fin, las recomendaciones sobre buenas prácticas en la administración segura de medicamentos para la salud para los niños. El infográfico fue evaluado por 13 especialistas y se obtuvo la coincidencia entre todos los ítems superior al 90 %. Conclusión El infográfico animado fue considerado como un recurso educativo válido, que podrá favorecer el proceso de enseñanza y aprendizaje de estudiantes de enfermería en lo que se refiere a la conducta de buenas prácticas en la administración de medicación en el área de la salud de los niños.

Abstract Objective To develop and assess an animated infographic as a teaching resource for teaching safe medication in children's health. Methods This is a methodological study consisting of the creation of an animated infographic about safe medication in children's health for students in higher education in nursing. The development of this digital educational technology followed four stages: planning, production, implementation and assessment. The criterion for assessment was greater than 90% agreement, analyzed using the Content Validity Index. Results The final version has 37 screens, which present the goals of the 3rdChallenge of the World Health Organization, adverse events, risk factors for the target audience and, finally, recommendations on good practices in safe medication administration in children's health. The infographic was assessed by 13 experts and there was an agreement between all items greater than 90%. Conclusion The animated infographic was considered a valid educational resource, which could favor the teaching-learning process of nursing students regarding the conduct of good practices in medication administration in children's health.

Telesimulation about home visits and child care: facilitators, barriers and perception of Nursing students / Telessimulação sobre visita domiciliar e cuidado infantil: facilidades, barreiras e percepções de estudantes de enfermagem / Telesimulación en visitas domiciliarias y cuidado infantil: facilidades, barreras y percepciones de estudiantes de enfermería

Abstract Objective: to evaluate the facilitators, barriers and perceptions of Nursing students in learning about home visiting and child care through Telesimulation during the COVID-19 pandemic. Method: a qualitative study to evaluate Telesimulation via computers, grounded on Kolb's theoretical model. A semi-structured questionnaire and the Student Satisfaction and Self-Confidence in Learning Scale were applied, with descriptive analysis and qualitative thematic analysis on the perceptions of 41 Nursing students. Results: the contextualized Telesimulation provided learning opportunities in dimensions of the pedagogical strategy, telesimulated scenario, communication and specificities of child care in home visits. It was considered a safe and dynamic activity that helped knowledge consolidation and reflective attitudes, proximity to reality, and develop interaction, observation and types of approaches. There were restrictions due to Internet connection failures. A large percentage of the students indicated good satisfaction and self-confidence level with learning in the scale applied. Conclusion: the real clinical situation with remote immersion allowed observation, decision-making, reflection and elaboration of conclusions, inherent to the experiential learning cycle. The set of elements of this Telesimulation created an environment that stimulated the interest of Nursing students for other learning stages, suggesting a space that strengthens knowledge and maintains dialogue with face-to-face practices.

Resumo Objetivo: avaliar as facilidades, barreiras e percepções de estudantes de enfermagem na aprendizagem sobre visita domiciliar e cuidado infantil por telessimulação na pandemia da COVID-19. Método: estudo qualitativo avaliativo de telessimulação por computador, fundamentado no modelo teórico de Kolb. Foram aplicados um questionário semiestruturado e a Escala de Satisfação de Estudantes e Autoconfiança na Aprendizagem, com análise descritiva e análise qualitativa temática sobre percepções de 41 graduandos de enfermagem. Resultados: a telessimulação contextualizada proporcionou oportunidades de aprendizagem em dimensões da estratégia pedagógica, cenário telessimulado, comunicação e especificidades do cuidado infantil em visita domiciliar. Atividade segura e dinâmica, auxiliou a solidificar conhecimentos e atitudes reflexivas, aproximação à realidade, desenvolvimento da interação, observação e tipos de abordagens. Houve restrições por falhas de conexão. Grande parte dos estudantes indicou níveis bons de satisfação e autoconfiança com a aprendizagem na escala aplicada. Conclusão: a situação clínica real com imersão remota permitiu observação, tomada de decisão, reflexão e elaboração de conclusões inerentes ao ciclo de aprendizagem experiencial. O conjunto de elementos desta telessimulação criou um ambiente que estimulou o interesse dos estudantes de enfermagem para outras etapas de aprendizagem, sugerindo um espaço que fortalece conhecimentos e que guarda interlocução com as práticas presenciais.

Resumen Objetivo: evaluar las facilidades, barreras y percepciones de estudiantes de enfermería en el aprendizaje sobre visita domiciliaria y cuidado infantil por telesimulación en la pandemia de COVID-19. Método: estudio cualitativo que evalúa la telesimulación por computadora, basado en el modelo teórico de Kolb. Se aplicó un cuestionario semiestructurado y la Escala de Satisfacción de los Estudiantes y Autoconfianza en el Aprendizaje, con análisis descriptivo y análisis temático cualitativo sobre las percepciones de 41 estudiantes de enfermería. Resultados: la telesimulación contextualizada brindó oportunidades de aprendizaje en los aspectos estrategia pedagógica, escenario telesimulado, comunicación y especificidades del cuidado infantil en visitas domiciliarias. Es una actividad segura y dinámica, que contribuyó a consolidar conocimientos y actitudes reflexivas, permitió un acercamiento a la realidad, el desarrollo de la interacción, observación y tipos de acercamientos. Hubo restricciones por fallas en la conexión. La mayoría de los estudiantes indicaron buenos niveles de satisfacción y confianza en sí mismos con el aprendizaje en la escala aplicada. Conclusión: la situación clínica real con participación a distancia permitió la observación, toma de decisiones, reflexión y elaboración de conclusiones inherentes al ciclo de aprendizaje experiencial. El conjunto de elementos de esta telesimulación creó un ambiente que estimuló el interés de los estudiantes de enfermería por otras etapas de aprendizaje, por lo que se considera un espacio que fortalece el conocimiento y dialoga con las prácticas presenciales.

Prebriefing in clinical simulation in nursing: scoping review / Prebriefing en simulación clínica en enfermería: revisión del alcance / O prebriefing na simulação clínica em enfermagem: revisão de escopo

ABSTRACT Objective To map the concept and structural elements of the prebriefing phase in clinical simulations in nursing. Method Scoping review with searches between May and June 2021 in the databases PubMed, Virtual Health Library, EMBASE, CINAHL, SCOPUS, Web of Science, CAPES Catalog of Theses and Dissertations, Brazilian Digital Library of Theses and Dissertations and Google Scholar, in portuguese, spanish and english, without time limit. Results 24 studies were selected. In 17 articles (70.8%) the authors used the spelling prebriefing (in italics and amended), to refer to the stage that precedes the simulation, including preparatory activities and guidance. Alternative methods for prebriefing were described (reflective practices, laboratories, games and videos). Conclusion There is no consensus regarding the concept and elements that constitute the prebriefing. This simulation stage contributes to participant satisfaction, participation and psychological safety, with better learning outcomes.

RESUMEN Objetivo Mapear el concepto y elementos estructurales de la fase prebriefing em simulaciones clínicas em enfermería. Método Scoping review con búsquedas entre mayo y junio de 2021 en las bases de datos PubMed/PMC, Virtual Health Library, EMBASE, CINAHL, SCOPUS, Web ofScience, Catálogo de Tesis y Disertaciones de la CAPES, Biblioteca Digital Brasileña de Tesis y Disertaciones y Google Scholar, en portugués, español e inglés, sin límite de tiempo. Resultados Se seleccionaron 24 estudios. En 17 artículos (70,8%) los autores utilizaron la ortografía prebriefing (en cursiva y corregida) para referirse a la etapa que precede la simulación, incluyendo actividades preparatorias y orientaciones. Se describieron métodos alternativos para el prebriefing (prácticas reflexivas, laboratorios, juegos y videos). Conclusión No existe consenso en cuanto al concepto y elementos que componen el prebriefing. Esta etapa de la simulación contribuye a la satisfacción, participación y seguridad psicológica del participante, con mejores resultados de aprendizaje.

RESUMO Objetivo Mapear o conceito e elementos estruturais da fase de prebriefing nas simulações clínicas em enfermagem. Método Scoping review com buscas, entre maio e junho de 2021, nas bases de dados Pub Med, Biblioteca Virtual em Saúde, EMBASE, CINAHL, SCOPUS e Web of Science, Catálogo de Teses & Dissertações da CAPES, Biblioteca Digital Brasileira de Teses e Dissertações e Google Scholar, nos idiomas português, espanhol e inglês, sem limite de tempo. Resultados Foram selecionados 24 estudos. Em 17 artigos (70,8%), os autores utilizaram a grafia prebriefing (em itálico e emendado), para se referir a etapa que antecede a simulação, incluindo atividades preparatórias e orientações. Foram descritos métodos alternativos para o prebriefing (práticas reflexivas, laboratórios, jogos e vídeos). Conclusão Não há consenso a respeito do conceito e dos elementos que compõem o prebriefing. Essa etapa da simulação contribui na satisfação, participação e segurança psicológica do participante, com melhores resultados de aprendizagem.

Rare Control of SIVmac239 Infection in a Vaccinated Rhesus Macaque.

Effector memory T cell (TEM) responses display potent antiviral properties and have been linked to stringent control of simian immunodeficiency virus (SIV) replication. Since recurrent antigen stimulation drives the differentiation of CD8+ T cells toward the TEM phenotype, in this study we incorporated a persistent herpesviral vector into a heterologous prime/boost/boost vaccine approach to maximize the induction of TEM responses. This new regimen resulted in CD8+ TEM-biased responses in four rhesus macaques, three of which controlled viral replication to <1,000 viral RNA copies/ml of plasma for more than 6 months after infection with SIVmac239. Over the course of this study, we made a series of interesting observations in one of these successful controller animals. Indeed, in vivo elimination of CD8αß+ T cells using a new CD8ß-depleting antibody did not abrogate virologic control in this monkey. Only after its CD8α+ lymphocytes were depleted did SIV rebound, suggesting that CD8αα+ but not CD8αß+ cells were controlling viral replication. By 2 weeks postinfection (PI), the only SIV sequences that could be detected in this animal harbored a small in-frame deletion in nef affecting six amino acids. Deep sequencing of the SIVmac239 challenge stock revealed no evidence of this polymorphism. However, sequencing of the rebound virus following CD8α depletion at week 38.4 PI again revealed only the six-amino acid deletion in nef. While any role for immunological pressure on the selection of this deleted variant remains uncertain, our data provide anecdotal evidence that control of SIV replication can be maintained without an intact CD8αß+ T cell compartment.

Ontogeny of the B- and T-cell response in a primary Zika virus infection of a dengue-naïve individual during the 2016 outbreak in Miami, FL.

Zika virus (ZIKV) is a mosquito-borne flavivirus of significant public health concern. In the summer of 2016, ZIKV was first detected in the contiguous United States. Here we present one of the first cases of a locally acquired ZIKV infection in a dengue-naïve individual. We collected blood from a female with a maculopapular rash at day (D) 5 and D7 post onset of symptoms (POS) and we continued weekly blood draws out to D148 POS. To establish the ontogeny of the immune response against ZIKV, lymphocytes and plasma were analyzed in a longitudinal fashion. The plasmablast response peaked at D7 POS (19.6% of CD19+ B-cells) and was undetectable by D15 POS. ZIKV-specific IgM was present at D5 POS, peaked between D15 and D21 POS, and subsequently decreased. The ZIKV-specific IgG response, however, was not detected until D15 POS and continued to increase after that. Interestingly, even though the patient had never been infected with dengue virus (DENV), cross-reactive IgM and IgG binding against each of the four DENV serotypes could be detected. The highest plasma neutralization activity against ZIKV peaked between D15 and D21 POS, and even though DENV binding antibodies were present in the plasma of the patient, there was neither neutralization nor antibody dependent enhancement (ADE) of DENV. Interestingly, ADE against ZIKV arose at D48 POS and continued until the end of the study. CD4+ and CD8+ T-cells recognized ZIKV-NS2A and ZIKV-E, respectively. The tetramer positive CD8+ T-cell response peaked at D21 POS with elevated levels persisting for months. In summary, this is the first study to establish the timing of the ontogeny of the immune response against ZIKV.

Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques.

Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasmablasts of a ZIKV-infected patient-SMZAb1, SMZAb2, and SMZAb5-directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fcγ receptor binding, thus eliminating potential therapy-mediated antibody-dependent enhancement. We administered a cocktail of these three nmAbs to nonhuman primates 1 day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum after challenge. Given that numerous antibodies have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses.

A human inferred germline antibody binds to an immunodominant epitope and neutralizes Zika virus.

The isolation of neutralizing monoclonal antibodies (nmAbs) against the Zika virus (ZIKV) might lead to novel preventative strategies for infections in at-risk individuals, primarily pregnant women. Here we describe the characterization of human mAbs from the plasmablasts of an acutely infected patient. One of the 18 mAbs had the unusual feature of binding to and neutralizing ZIKV despite not appearing to have been diversified by affinity maturation. This mAb neutralized ZIKV (Neut50 ~ 2 µg/ml) but did not react with any of the four dengue virus serotypes. Except for the expected junctional diversity created by the joining of the V-(D)-J genes, there was no deviation from immunoglobulin germline genes. This is a rare example of a human mAb with neutralizing activity in the absence of detectable somatic hypermutation. Importantly, binding of this mAb to ZIKV was specifically inhibited by human plasma from ZIKV-exposed individuals, suggesting that it may be of value in a diagnostic setting.