Guidelines for plaque-reduction neutralization testing of human antibodies to dengue viruses [2007] [World Health Organization]

Details

• Corporate Authors:
  World Health Organization (WHO) ; Department of Immunization, Vaccines and Biologicals ; Initiative for Vaccine Research
• Description:
  Through the Steering Committee on Dengue and other Flavivirus Vaccines, the World Health Organization (WHO) has had a long-standing commitment to facilitate and to guide research and development of vaccines for medically important flaviviruses. Recently, the Paediatric Dengue Vaccine Initiative (PDVI) was formed to accelerate the development, testing, and introduction of dengue (DEN) vaccines worldwide, partnering with WHO in this important public health effort. There are now a variety of DEN vaccines in various stages of the developmental pipeline. In an attempt to make inter-laboratory information more directly comparable, WHO and PDVI initiated a program to harmonize the procedures used for the plaque-reduction neutralization test (PRNT). The PRNT is the most common assay used to measure neutralizing antibody. The presence of antibody is believed to be most relevant for determining protective anti-DEN virus (DENV) immunity. While other neutralizing antibody assays are being considered for use in large scale vaccine field trials, the PRNT is still considered to be the laboratory standard against which other neutralizing antibody assays should be compared (Martin et al., 2006; Vorndam and Beltran, 2002). The need for PRNT harmonization has been identified at several consultations of WHO and PDVI. In addition to these meetings, WHO has conducted a collaborative study with the aim of establishing a reference panel of dengue infection-immune sera. These data revealed considerable inter-laboratory variability due to different methods employed to perform and analyse the PRNT data, corroborating the need for establishing a more harmonized approach to DENV PRNT. These guidelines are a direct result of all of these efforts.
  
  The levels of flavivirus-neutralizing antibody titters in the serum of vaccinated, or infection-immune individuals, correlates best with protection from subsequent virus infection. However, the lack of a standardized PRNT poses a hurdle for comparing data between vaccine trials and testing laboratories, and defining a threshold value to use as a true serological correlate of protection. The purpose of these guidelines is to: 1) provide scientific insight into the biology of the flavivirus neutralization test; 2) provide guidelines for test harmonization, and; 3) provide minimal recommendations for a test protocol for laboratories which might be interested in establishing the test. It must be remembered that the PRNT is, above all, a biological assay, and as such will always have a certain degree of inter-laboratory variation. Due to this and other lab-to-lab variability, such as specific vaccine design approaches, strains used for vaccine development, and other unique manufacturing requirements, these guidelines will not mandate the use of a single standardized protocol. Ultimately, the definition of a protective level of vaccine-induced neutralizing antibody by whatever suitable assay will need to be validated in a vaccine efficacy trial.
  
  
• Content Notes:
  Publicaiton date from document properties.
• Subjects:
  Antibodies Dengue Neutralization Tests
• DOI:
  https://iris.who.int/handle/10665/69687
• Publisher:
  World Health Organization (WHO)
• Document Type:
  Text
• Genre:
  Guideline
• Pages in Document:
  36 pdf pages
• Citation:
  World Health Organization. (‎2007)‎. Guidelines for plaque reduction neutralization testing of human antibodies to dengue viruses. World Health Organization. https://iris.who.int/handle/10665/69687
• Collection(s):
  Guidelines and Recommendations
• Main Document Checksum:
  urn:sha-512:eaac83e58a4b0c6ebf5b20b0879db9a14188f880190dc3f407db1a09bd0ae8e79ad4ebe1d8dc22c40a60d8b9daba92f2f71e7c2f52d985115ff55b14c38a8f5c
• Download URL:
  https://stacks.cdc.gov/view/cdc/177370/cdc_177370_DS1.pdf
• File Type:
  [PDF - 709.64 KB ]