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1.
AIDS Res Hum Retroviruses ; 40(11): 615-621, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38973467

RESUMO

The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, consistency, and validity, and the safety of the clinical research or trial participants and laboratory staff, as well as ensures adherence to regulatory requirements. This article describes the application of the DAIDS GCLP Guidelines, the DAIDS Integrated Laboratory Oversight Framework, and the coordinated efforts of the collaborative oversight team of laboratory experts to support and monitor the performance of over 175 participating laboratories worldwide. Data from two self-administered online surveys conducted in 2017 and 2023 assessed the laboratory staff's experience implementing the GCLP Guidelines. The results of the 2017 survey were instrumental in informing changes to GCLP audit activities and promoting harmonization in the approach to laboratory oversight. A key finding from the 2023 survey results is the preference for hybrid GCLP training, encompassing face-to-face and online modules. Overall, both surveys acknowledged satisfaction with applying and implementing GCLP Guidelines. The need to effectively disseminate information about DAIDS laboratory oversight requirements to support the improved implementation of GCLP Guidelines was notable from both survey results. The collaborative team of laboratory experts and the integrated oversight approach promote knowledge-sharing and accountability to support the application of the GCLP Guidelines and compliance monitoring. The systematic implementation of the integrated laboratory oversight activities helped identify valuable lessons for improving laboratory performance and opportunities to strengthen quality oversight for laboratories participating in clinical research or trials.


Assuntos
Laboratórios Clínicos , Humanos , Inquéritos e Questionários , Laboratórios Clínicos/normas , Pesquisa Biomédica/normas , Fidelidade a Diretrizes/estatística & dados numéricos
7.
Commun Med (Lond) ; 2: 110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045906

RESUMO

The rapid development of COVID-19 vaccines and their deployment in less than a year is an unprecedented scientific, medical, and public health achievement. This rapid development leveraged knowledge from decades of HIV/AIDS research and advances. However, the search for an HIV vaccine that would contribute to a durable end to the HIV pandemic remains elusive. Here, we draw from the US government experience and highlight lessons learned from COVID-19 vaccine development, which include the importance of public-private partnerships, equitable inclusion of populations impacted by the infectious pathogen, and continued investment in basic research. We summarize key considerations for an accelerated and re-energized framework for developing a safe and efficacious HIV vaccine.

8.
Vaccine ; 39(37): 5233-5239, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34366145

RESUMO

Modern vaccinology has experienced major conceptual and technological advances over the past 30 years. These include atomic-level structures driving immunogen design, new vaccine delivery methods, powerful adjuvants, and novel animal models. In addition, utilizing advanced assays to learn how the immune system senses a pathogen and orchestrates protective immunity has been critical in the design of effective vaccines and therapeutics. The National Institute of Allergy and Infectious Diseases of the National Institutes of Health convened a workshop in September 2020 focused on next generation assays for vaccine development (Table 1). The workshop focused on four critical pathogens: severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and human immunodeficiency virus (HIV)-which have no licensed vaccines-and tuberculosis (TB) and influenza-both of which are in critical need of improved vaccines. The goal was to share progress and lessons learned, and to identify any commonalities that can be leveraged to design vaccines and therapeutics.


Assuntos
COVID-19 , Tuberculose , Animais , Humanos , Laboratórios , SARS-CoV-2 , Tuberculose/prevenção & controle , Estados Unidos , Vacinologia
9.
Heliyon ; 7(1): e06005, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33532641

RESUMO

The HIV Vaccine Trials Network (HVTN) is the world's largest publicly funded, multi-disciplinary international collaboration facilitating the development of vaccines to prevent HIV/AIDS and has conducted the vast majority of HIV/AIDS clinical trials since its inception in 1999. Although scientific findings from the program have been published in scholarly journals, the impact of a large scientific research network such as the HVTN on the HIV/AIDS vaccine field has not been assessed. This paper describes and elucidates the productivity, influence, and collaboration among HVTN researchers over the last two decades. Our analyses indicate that the HVTN has funded a large number of HIV/AIDS vaccine safety and efficacy clinical trials through a strong global network of clinical sites. In addition, several metrics indicate HVTN researchers also published original research articles that are influential in the HIV vaccine field. Scientific research collaboration is critically important in a complex and multidisciplinary field such as HIV vaccine development as it allows improved sharing of knowledge and expertise as well as the pooling of resources and data. We found that collaboration in the HIV vaccine field increased during this time period and collaboration among HVTN authors increased even more. Combining these productivity, influence, and collaboration metrics with research outcomes can provide a comprehensive assessment of large complex programs such as the HVTN.

10.
Vaccine ; 38(2): 187-193, 2020 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-31759734

RESUMO

Bioengineering approaches grounded in immunology have the potential for the discovery and development of a successful HIV vaccine. The overarching goal is to engineer immunity through a fusion of immunology with bioengineering to create novel strategies for the design, development and delivery of vaccines based on the controlled modulation of the immune system. To foster these collaborations, the National Institute of Allergy and Infectious Diseases (NIAID) and National Institute of Biomedical Imaging and Bioengineering (NIBIB) brought together a group of experts (see Table 1) from these diverse fields for a workshop in September 2018 to: (1) engage the engineering, immunology, and HIV vaccinology communities to dialogue on the topic of an HIV vaccine and; (2) generate a framework of new and innovative research avenues to explore in HIV vaccinology between knowledge stakeholders and problem solvers.


Assuntos
Vacinas contra a AIDS/imunologia , Bioengenharia , Pesquisa Biomédica/organização & administração , Infecções por HIV/prevenção & controle , Comportamento Cooperativo , Desenvolvimento de Medicamentos , Humanos , National Institute of Allergy and Infectious Diseases (U.S.) , National Institute of Biomedical Imaging and Bioengineering (U.S.) , Estados Unidos , Vacinologia/organização & administração
11.
PLoS Pathog ; 15(2): e1007567, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30789961

RESUMO

Most studies of T lymphocytes focus on recognition of classical major histocompatibility complex (MHC) class I or II molecules presenting oligopeptides, yet there are numerous variations and exceptions of biological significance based on recognition of a wide variety of nonclassical MHC molecules. These include αß and γδ T cells that recognize different class Ib molecules (CD1, MR-1, HLA-E, G, F, et al.) that are nearly monomorphic within a given species. Collectively, these T cells can be considered "unconventional," in part because they recognize lipids, metabolites, and modified peptides. Unlike classical MHC-specific cells, unconventional T cells generally exhibit limited T-cell antigen receptor (TCR) repertoires and often produce innate immune cell-like rapid effector responses. Exploiting this system in new generation vaccines for human immunodeficiency virus (HIV), tuberculosis (TB), other infectious agents, and cancer was the focus of a recent workshop, "Immune Surveillance by Non-classical MHC Molecules: Improving Diversity for Antigens," sponsored by the National Institute of Allergy and Infectious Diseases. Here, we summarize salient points presented regarding the basic immunobiology of unconventional T cells, recent advances in methodologies to measure unconventional T-cell activity in diseases, and approaches to harness their considerable clinical potential.


Assuntos
Vigilância Imunológica/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Animais , Antígenos , Antígenos HLA , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Linfócitos T/imunologia
12.
J Immunol Methods ; 409: 62-71, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24801479

RESUMO

Luminex bead array assays are widely used for rapid biomarker quantification due to the ability to measure up to 100 unique analytes in a single well of a 96-well plate. There has been, however, no comprehensive analysis of variables impacting assay performance, nor development of a standardized proficiency testing program for laboratories performing these assays. To meet this need, the NIH/NIAID and the Cancer Immunotherapy Consortium of the Cancer Research Institute collaborated to develop and implement a Luminex assay proficiency testing program as part of the NIH/NIAID-sponsored External Quality Assurance Program Oversight Laboratory (EQAPOL) at Duke University. The program currently monitors 25 domestic and international sites with two external proficiency panels per year. Each panel includes a de-identified commercial Luminex assay kit with standards to quantify human IFNγ, TNFα, IL-6, IL-10 and IL-2, and a series of recombinant cytokine-spiked human serum samples. All aspects of panel development, testing and shipping are performed under GCLP by EQAPOL support teams. Following development testing, a comprehensive site proficiency scoring system comprised of timeliness, protocol adherence, accuracy and precision was implemented. The overall mean proficiency score across three rounds of testing has remained stable (EP3: 76%, EP4: 75%, EP5: 77%); however, a more detailed analysis of site reported results indicates a significant improvement of intra- (within) and inter- (between) site variation, suggesting that training and remediation for poor performing sites may be having a positive impact on proficiency. Through continued proficiency testing, identification of variables affecting Luminex assay outcomes will strengthen efforts to bring standardization to the field.


Assuntos
Citocinas/sangue , Ensaios de Triagem em Larga Escala/normas , Laboratórios/normas , Ensaio de Proficiência Laboratorial/normas , Monitorização Imunológica/normas , Estudos Multicêntricos como Assunto/normas , Biomarcadores/sangue , Comportamento Cooperativo , Fidelidade a Diretrizes/normas , Humanos , Cooperação Internacional , Variações Dependentes do Observador , Guias de Prática Clínica como Assunto/normas , Valor Preditivo dos Testes , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Controle de Qualidade , Melhoria de Qualidade/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Padrões de Referência , Reprodutibilidade dos Testes , Manejo de Espécimes/normas , Fatores de Tempo , Fluxo de Trabalho
13.
J Immunol Methods ; 409: 107-16, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24787274

RESUMO

A large repository of cryopreserved peripheral blood mononuclear cells (PBMCs) samples was created to provide laboratories testing the specimens from human immunodeficiency virus-1 (HIV-1) vaccine clinical trials the material for assay development, optimization, and validation. One hundred thirty-one PBMC samples were collected using leukapheresis procedure between 2007 and 2013 by the Comprehensive T cell Vaccine Immune Monitoring Consortium core repository. The donors included 83 human immunodeficiency virus-1 (HIV-1) seronegative and 32 HIV-1 seropositive subjects. The samples were extensively characterized for the ability of T cell subsets to respond to recall viral antigens including cytomegalovirus, Epstein-Barr virus, influenza virus, and HIV-1 using Interferon-gamma (IFN-γ) enzyme linked immunospot (ELISpot) and IFN-γ/interleukin 2 (IL-2) intracellular cytokine staining (ICS) assays. A subset of samples was evaluated over time to determine the integrity of the cryopreserved samples in relation to recovery, viability, and functionality. The principal results of our study demonstrate that viable and functional cells were consistently recovered from the cryopreserved samples. Therefore, we determined that this repository of large size cryopreserved cellular samples constitutes a unique resource for laboratories that are involved in optimization and validation of assays to evaluate T, B, and NK cellular functions in the context of clinical trials.


Assuntos
Vacinas contra a AIDS/uso terapêutico , Bancos de Espécimes Biológicos/normas , Infecções por HIV/terapia , HIV-1/imunologia , Testes Imunológicos/normas , Ensaio de Proficiência Laboratorial/normas , Leucócitos Mononucleares/imunologia , Monitorização Imunológica/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Adolescente , Adulto , Biomarcadores/sangue , Sobrevivência Celular , Comportamento Cooperativo , Criopreservação/normas , Citocinas/sangue , ELISPOT/normas , Feminino , Fidelidade a Diretrizes/normas , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Testes de Liberação de Interferon-gama/normas , Cooperação Internacional , Leucaférese/normas , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Guias de Prática Clínica como Assunto/normas , Valor Preditivo dos Testes , Controle de Qualidade , Reprodutibilidade dos Testes , Manejo de Espécimes/normas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
J Immunol Methods ; 409: 31-43, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24685833

RESUMO

The interferon-gamma enzyme-linked immunospot (IFN-γ ELISpot) assay has been developed and used as an end-point assay in clinical trials for infectious diseases and cancer to detect the magnitude of antigen-specific immune responses. The ability to compare data generated by different laboratories across organizations is pivotal to understand the relative potency of different therapeutic and vaccine strategies. We developed an external proficiency program for the IFN-γ ELISpot assay that evaluates laboratory performance based on five parameters: timeliness for data reporting; ability to handle cellular samples; detection of background (non-specific) responses; accuracy to consensus of the results; and precision of the measurements. Points are awarded for each criterion, and the sum of the points is used to determine a numeric and adjectival performance rating. Importantly, the evaluation of the accuracy to the consensus mean for the detection of antigen-specific responses using laboratory-specific procedures informs each laboratory and its sponsor on the degree of concordance of its results with those obtained by other laboratories. This study will ultimately provide the scientific community with information on how to organize and implement an external proficiency program to evaluate longitudinally the performance of the participating laboratories and, therefore, fulfill the requirements of the GCLP guidelines for laboratories performing end-point IFN-γ ELISpot assay for clinical trials.


Assuntos
Ensaios Clínicos como Assunto/normas , ELISPOT/normas , Testes de Liberação de Interferon-gama/normas , Laboratórios/normas , Ensaio de Proficiência Laboratorial/normas , Monitorização Imunológica/normas , Indicadores de Qualidade em Assistência à Saúde/normas , Consenso , Comportamento Cooperativo , Fidelidade a Diretrizes/normas , Humanos , Cooperação Internacional , Estudos Longitudinais , Variações Dependentes do Observador , Guias de Prática Clínica como Assunto/normas , Valor Preditivo dos Testes , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Controle de Qualidade , Reprodutibilidade dos Testes , Manejo de Espécimes/normas , Fatores de Tempo
15.
Nat Med ; 19(2): 143-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23389614

RESUMO

CD4(+) T cells can perform a panoply of tasks to shape an effective response against a pathogen. Limited attention has been paid to the potential importance of functional CD4(+) T cell responses in the context of the development of next-generation vaccines, including HIV vaccines. Many CD4(+) T cell functions are newly appreciated and only partially understood. A workshop was held as a forum to bring together a small group of experts to exchange ideas on the role of CD4(+) T cells in developing durable functional antibody responses, via follicular helper T cells, as well as on the roles of CD4(+) T cells in other aspects of protective immunity. Here we discuss whether CD4(+) T cell responses may represent a beneficial component of an efficacious HIV vaccine.


Assuntos
Vacinas contra a AIDS/imunologia , Linfócitos T CD4-Positivos/imunologia , Anticorpos Neutralizantes/biossíntese , Anticorpos Anti-HIV/biossíntese , Humanos , Receptores CXCR5/análise
16.
J Immunol Methods ; 375(1-2): 57-67, 2012 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-21968254

RESUMO

Recent advances in assay technology have led to major improvements in how HIV-1 neutralizing antibodies are measured. A luciferase reporter gene assay performed in TZM-bl (JC53bl-13) cells has been optimized and validated. Because this assay has been adopted by multiple laboratories worldwide, an external proficiency testing program was developed to ensure data equivalency across laboratories performing this neutralizing antibody assay for HIV/AIDS vaccine clinical trials. The program was optimized by conducting three independent rounds of testing, with an increased level of stringency from the first to third round. Results from the participating domestic and international laboratories improved each round as factors that contributed to inter-assay variability were identified and minimized. Key contributors to increased agreement were experience among laboratories and standardization of reagents. A statistical qualification rule was developed using a simulation procedure based on the three optimization rounds of testing, where a laboratory qualifies if at least 25 of the 30 ID50 values lie within the acceptance ranges. This ensures no more than a 20% risk that a participating laboratory fails to qualify when it should, as defined by the simulation procedure. Five experienced reference laboratories were identified and tested a series of standardized reagents to derive the acceptance ranges for pass-fail criteria. This Standardized Proficiency Testing Program is the first available for the evaluation and documentation of assay equivalency for laboratories performing HIV-1 neutralizing antibody assays and may provide guidance for the development of future proficiency testing programs for other assay platforms.


Assuntos
Anticorpos Neutralizantes/análise , Anticorpos Anti-HIV/análise , HIV-1/imunologia , Ensaio de Proficiência Laboratorial/normas , Testes de Neutralização/normas , Vacinas contra a AIDS/imunologia , Anticorpos Neutralizantes/imunologia , Linhagem Celular Tumoral , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Controle de Qualidade , Padrões de Referência
17.
J Immunol Methods ; 363(2): 143-57, 2011 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-20727897

RESUMO

When evaluating candidate prophylactic HIV and cancer vaccines, intracellular cytokine staining (ICS) assays that measure the frequency and magnitude of antigen-specific T-cell subsets are one tool to monitor immunogen performance and make product advancement decisions. To assess the inter-laboratory assay variation among multiple laboratories testing vaccine candidates, the NIH/NIAID/DAIDS in collaboration with BD Biosciences implemented an ICS Quality Assurance Program (QAP). Seven rounds of testing have been conducted in which 16 laboratories worldwide participated. In each round, IFN-γ, IL-2 and/or TNF-α responses in CD4+ and CD8+ T-cells to CEF or CMV pp65 peptide mixes were tested using cryopreserved peripheral blood mononuclear cells (PBMC) from CMV seropositive donors. We found that for responses measured above 0.2%, inter-laboratory %CVs were, on average, 35%. No differences in inter-laboratory variation were observed if a 4-color antibody cocktail or a 7-color combination was used. Moreover, the data allowed identification of important sources of variability for flow cytometry-based assays, including: number of collected events, gating strategy and instrument setup and performance. As a consequence, in this multi-site study we were able to define pass and fail criteria for ICS assays, which will be adopted in the subsequent rounds of testing and could be easily extrapolated to QAP for other flow cytometry-based assays.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citometria de Fluxo/métodos , Interferon gama/sangue , Interleucina-2/sangue , Fator de Necrose Tumoral alfa/sangue , Citometria de Fluxo/normas , Corantes Fluorescentes/química , Humanos , Leucócitos Mononucleares/imunologia , Variações Dependentes do Observador , Fosfoproteínas/imunologia , Proteínas de Saccharomyces cerevisiae/imunologia , Estatísticas não Paramétricas , Proteínas de Transporte Vesicular/imunologia , Proteínas da Matriz Viral/imunologia
18.
J Infect Dis ; 202 Suppl 2: S267-9, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20846032

RESUMO

This supplemental issue of the Journal of Infectious Diseases is devoted to the important topic of primary human immunodeficiency virus type 1 (HIV-1) infection. It was prompted by the planning of the Acute HIV-1 Infection Meeting in Boston in September 2009, at which leading scientists and practitioners gathered to discuss new insights into the early, critical events of HIV-1 infection. The reviews that follow underline the current state of the field with regard to transmission biology of HIV-1; the clinical presentation, diagnosis, and management of primary HIV-1 infection; the pathogenesis of primary HIV-1 infection; and innate and adaptive immune responses to the virus. We trust that these findings have the potential to influence the development of effective vaccine strategies.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/patologia , HIV-1/isolamento & purificação , HIV-1/patogenicidade , Vacinas contra a AIDS/imunologia , Pesquisa Biomédica/tendências , Infecções por HIV/imunologia , Infecções por HIV/terapia , HIV-1/imunologia , Humanos
19.
J Infect Dis ; 201 Suppl 1: S1-6, 2010 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-20225941

RESUMO

The introduction of serological point-of-care assays 10 years ago dramatically changed the way that human immunodeficiency virus (HIV) infection was identified and diagnosed. Testing at the point of care has lead to a dramatic increase in the number of individuals who are screened and, most importantly, receive their HIV test result. As the AIDS epidemic continues to mature and scientific advances in prevention and treatment are evaluated and implemented, there is a need to identify acute (viremic preseroconversion) infections and to discriminate "window phase" infections from those that are serologically positive, especially in resource-limited settings, where the majority of vulnerable populations reside and where the incidence of HIV infection is highest. Rapid testing methods are now at a crossroads. There is opportunity to implement and evaluate the incremental diagnostic usefulness of new test modalities that are based on sophisticated molecular diagnostic technologies and that can be performed in settings where laboratory infrastructure is minimal. The way forward requires sound scientific judgment and an ability to further develop and implement these tests despite a variety of technical, social, and operational hurdles, to declare success.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , HIV/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Humanos , Sistemas Automatizados de Assistência Junto ao Leito
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