Developing a safe and effective vaccine requires laboratories analyzing samples from clinical trials to follow good clinical laboratory practices (GCLP). The laboratories use sensitive, accurate, reproducible, and quantitative assays that provide clear measurements of vaccine-induced immune responses to allow comparison of data across multiple sites and prioritization of the most promising vaccines. To define the correlates of protection, new and innovative approaches will be required to correlate immune response with vaccine-induced protection. The central components of vaccine assessment include
All phases of clinical trials of a candidate HIV vaccine safety testing and monitoring help determine how well the volunteers tolerate the vaccine. Routine safety tests include blood and urine sample analyses that check blood cell counts, hemoglobin levels, kidney function, and liver function as well as screening for infection with syphilis, HIV, and/or hepatitis B and C viruses. These tests are performed by laboratories that meet Clinical Laboratory Improvements Amendments certification and accreditation by the College of American Pathologists (CAP), standards which are normative for all clinical laboratories in the United States. Similarly, international laboratories performing assays for HIV vaccine trials meet local accreditation and are enrolled in CAP and in external quality assurance programs to ensure performance standards.
To ensure the highest possible specimen quality among different clinical settings, optimal methods are required to collect, process, ship, and store blood specimens to ensure appropriate blood cell recovery, viability, and function. Site-associated laboratories separate and cryopreserve serum and peripheral blood mononuclear cells (PBMC) from blood within 6 to 8 hours after collection by venipuncture. Appropriate sample volumes are optimally handled to perform immunological evaluations that indicate immune resistance to HIV infection.
The immunological objective of HIV vaccines is to elicit effective humoral, cellular, and mucosal immune responses. To assess the effectiveness of the new generation of vaccines, scientists have expended considerable efforts into developing and standardizing reliable assays that analyze and quantify vaccine-induced immune responses. Specimens from vaccine clinical trials—PBMCs and serum or plasma—are currently evaluated using four optimized and validated assays of immune response to the vaccine. The assays are performed at designated "central" laboratories under internationally accepted GCLP guidelines. The central laboratories also follow approved Quality Assurance and Quality Control protocols and have Standard Operating Procedures for the assays. These labs participate in external proficiency testing administered by CAP and the NIAID Division of AIDS (DAIDS) as a means to ensure confidence in the quality of results, assess assay proficiency, and contribute to the standardization of assay performance among laboratories. The four validated assays include:
DAIDS has established an external quality assurance (EQA) program for laboratories performing immunogenicity assays as part of NIAID-sponsored clinical trials. The EQA program for ELISpot and ICS assays is described below, and programs for other testing such as viral suppression, proliferation, and virus neutralization are in development. Participation in these programs for protocol-mandated assays is a DAIDS requirement.
In addition to the validated assays, there is a need to incorporate new technology platforms into clinical trials of candidate HIV vaccines to comprehensively characterize vaccine-induced responses and to define the correlates of immune protection in large-scale efficacy trials. To accommodate these aims, additional assays currently under development include:
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Last Updated July 08, 2008