Strong HIV-1-Specific T Cell Responses in HIV-1-Exposed Uninfected Infants and Neonates Revealed after Regulatory T Cell Removal

BACKGROUND: In utero transmission of HIV-1 occurs on average in only 3%–15% of HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus, despite potential exposure, the majority of infants remain uninfected. Weak HIV-1-specific T-cell responses have been detected in children exposed to HIV-1, and potentially contribute to protection against infection. We, and others, have recently shown that the removal of CD4(+)CD25(+) T-regulatory (Treg) cells can reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults. Here, we hypothesized that Treg cells could suppress HIV-1-specific immune responses in young children. METHODOLOGY/PRINCIPAL FINDINGS: We studied two cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation, and cell-mediated immune responses. We detected high levels of CD4(+)CD25(+)CD127(−) Treg cells and low levels of CD4(+) and CD8(+) T cell activation in the cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses in all of the children exposed to the virus. These T-cell responses were not seen in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of CD4(+)CD25(+) Treg cells from the cord blood of EU newborns strikingly augmented both CD4(+) and CD8(+) HIV-1-specific immune responses. CONCLUSIONS/SIGNIFICANCE: This study provides new evidence that EU infants can mount strong HIV-1-specific T cell responses, and that in utero CD4(+)CD25(+) T-regulatory cells may be contributing to the lack of vertical transmission by reducing T cell activation

MICROBIAL INHIBITORS EVALUATED BY DELVO-TEST IN MILK FOR CONSUMPTION IN SÃO PAULO STATE (BRAZIL)

Foram testadas 648 amostras de leite para presença de inibidores microbianos através do Delvo teste. Destas, 12,72% foram positivas. Os tipos de leite revelaram: presença de inibidores em 44 amostras do tipo B (17,32%), em 8 do tipo C (8,25%), em 21 do tipo especial -3,2% de gordura (11,05%), em 5 do tipo magro - 2% de gordura (18,52%) e em 9'de leite cru, não pasteurizado (8,82%). As demais amostras, que incluem 14 do tipo A num total de 597 amostras, foram negativas para a presença de inibidores, avaliados pelo Delvo teste. A região de Bauru e Sorocaba revelaram número significativamente maior de amostras positivas com relação às demais regiões (respectivamente, 5 amostras positivas em 9 analisadas e 21 positivas em 135 analisadas). Six hundred and eighty four milk samples were tested for anti-microbial substances by the Delvo-test. Presented positive results 12,72%. Evaluation by classes of milk, revealed positive: 44 samples from type B 17,32%, 8 type C 8,25%, 21 special type-3,2% fat content 11,05%, 5 of 2% of fat content 18,52% and 9 non pasteurized 8,82%. AlI others 597 samples, that includes 14 type A, resulted negative for anti-microbial substances by the Delvo-test. Bauru and Sorocaba regions showed a significantly high number of positive samples when compared to others regions (respectively 5 positives among 9 and 21 among 135 samples analysed)

Data_Sheet_1_Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.PDF

IntroductionThe COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.MethodsAt the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.ResultsOver the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020–2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.DiscussionResearch is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.</p