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STANDARDISATION OF HIV NEUTRALISATION ASSAYS TO BE USED IN VACCINE RESEARCH AND CLINICAL TRIALS

Final Report Summary - NeutNet (STANDARDISATION OF HIV NEUTRALISATION ASSAYS TO BE USED IN VACCINE RESEARCH AND CLINICAL TRIALS)

The relevance of neutralising antibody-mediated protection against human immunodeficiency virus (HIV) infection and disease remains to be elucidated. While antibodies are known to play an important role in protection against viral diseases such as polio, hepatitis, measles and influenza, the relevance of neutralising antibodies in HIV-1 protection and pathogenesis remains to be further defined.

Production of an antibody response with broad neutralising activity against primary isolates of multiple HIV-1 subtypes continues to be a desired characteristic for candidate HIV vaccines. To support the evolution of phase I, II, and III human vaccine trials testing new HIV immunogens, it will be important to standardise as far as possible and practicable and apply high throughput, sensitive, specific and reproducible HIV neutralisation assays. Numerous in vitro neutralisation assays have been developed, each one with different variables and endpoints.

NeutNet started as a group of 13 participants from all over the world with the intention of coordinating activities aimed at standardising methods for the measurement of neutralising antibodies to HIV-1 for use in human clinical trials of candidate AIDS vaccines. The overall goal of NeutNet included the organisation of an initial study with the most relevant neutralisation methods and a panel of well characterised and common reagents, so as to define appropriate reference controls for neutralisation assays. The evaluation of such as study should serve as a basis for a subsequent study with polyclonal serologic reagents in order to gain an understanding of the prerequisites to accurately and reproducibly measure HIV-1 functional antibodies for HIV protection and pathogenesis.

A workshop jointly organised with WHO/UNAIDS has provided a forum for the discussion of the results of the actions of NeutNet with a larger body of workers in the field and for sharing of information at a global level.

During the two years NeutNet has enlarged the group of participants and is now composed of 18 members. It can provide seven different types of neutralisation assays with an array of variants. It has organised an initial study to compare different neutralisation methods using a number of well known monoclonal antibodies against a panel of well characterised viruses and the envelope clones.

Lastly, NeutNet organised a website maintained by NIBSC and a subsequent study to compare polyclonal serologic reagents such as individual and pooled sera/plasma from HIV-1 infected and uninfected donors and their immunoglobin fraction.