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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.

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., Bibliometrics; Outcomes; HIV vaccine; HIV

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.

Development of a safe and preventive HIV-1 vaccine is a high priority. Recent advances in HIV vaccine development include an improved understanding of HIV envelope structure, development of techniques that enable a detailed analysis of vaccine-induced immune responses in humans, expansion of the pipeline of promising candidate vaccines, and completion of the first vaccine efficacy trials. A common feature of several preventive vaccine strategies in early clinical trials is their ability to attenuate clinical disease rather than completely prevent HIV infection in nonhuman primates. One or more candidate vaccines will likely advance into efficacy trials within the next few years, while efforts to identify new designs that induce broadly neutralizing antibodies continue with incremental success.

A workshop entitled "Early Phases of HIV-1 Infection" was held to review current research on the immunological and virological aspects of early phases of HIV infection in humans and in ani...

A Workshop on Neutralization of HIV-1: Technology and reagents for analysis of prophylactic vaccines clinical trials, sponsored by the Food and Drug Administration (FDA) and the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), was held on April 19–20, 1993, in Bethesda, Maryland. This workshop brought together researchers who are involved in the development, testing, and evaluation of HIV-1 prophylactic vaccines. The major objectives were (1) to discuss critically the different neutralization and binding assays that are currently used in the evaluation of immune sera; (2) to identify assays that will measure the "most relevant" antibodies, which are likely to predict neutralization of primary isolates; and (3) to identify well-characterized reference reagents, which could be used to standardize neutralization assays used in laboratories around the world.

The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), sponsored a Workshop on HIV-Mediated Defects in Immune Regulation on September 29–30, 1993. Workshop par...

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.

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.

We used an external quality assurance (EQA) panel to assess laboratory competency and comparability when performing ELISPOT assays in support of human immunodeficiency virus type 1 (HIV-1) vaccine trials. Cell recovery, viability, and frequency of interferon-gamma (IFN-gamma)-secreting cells after antigen stimulation were obtained from 11 laboratories on a coded panel of 11 peripheral blood mononuclear cell samples. The median recovery and viability before plating for all samples were 35% and 86%, respectively, with notable interlaboratory and intrasample variability. Empirical as well as statistical analysis methods were used to define positive ELISPOT responses. Remarkable concordance between laboratories was obtained in defining a qualitative assessment of responder/nonresponder status to antigens, but the frequency of responding cells varied among the laboratories. This study highlights the need for better standardization of protocols and reagents to obtain reliable and reproducible data that may support immunogenicity studies, vaccine regulatory submissions, and licensure.

The discovery of an HIV-1 vaccine is a high priority. Recent advances in HIV vaccine development include an improved understanding about virus biology and structure, and the development of quantitative techniques that enable a detailed analysis of vaccine-induced immune responses in humans. The preclinical vaccine pipeline looks healthy, and a common feature of the new vaccine strategies is their ability to attenuate clinical disease rather than prevent HIV infection in nonhuman primates. Human clinical trials to evaluate the safety and immunogenicity of these vaccine candidates and strategies are being actively pursued.