When Zika virus was announced as a Public Health Emergency of International Concern in February 2016, the newly formed Emerging Viruses Group at NIBSC had only just completed a project to produce WHO International Standards (IS) for Ebola. As before, the WHO held a teleconference between the WHO Collaborating Centres to identify who could rapidly respond to the emergency and produce reference materials that would be needed for assay calibration and harmonisation. The group at NIBSC was able to respond affirmatively through experience learnt developing Ebola antibody and NAT standards for serological assays and PCR diagnostics, respectively. Access to source materials is often a major obstacle We soon learnt that sera/plasma and viruses from Brazil were off the table, so other routes had to be explored. Fortunately, The Paul Ehrlich Institute had Asian lineage virus stocks and they were tasked with producing a NAT standard from an inactivated virus preparation. That left NIBSC tasked with producing the 1st International Standard for Zika antibody.
An optimal antibody standard is that which behaves as closely as possible to a clinical sample and therefore human serum/plasma from convalescent individuals is desired. Collecting these materials is not straightforward. It’s perhaps optimistic to expect that a recently infected individual is willing to provide a blood sample, but it’s another scenario entirely to expect that the donor provides in excess of 200mL at one time. Large volumes are needed to produce several thousand vials of a WHO standard so that they are available as a traceable assay calibrant for many years. This requires the donation of serum/plasma volumes in excess of 1000mL. To achieve this, we can pool donor samples, but where can we source infected individuals? As previously for Ebola, the generous nature of various institutions came to the fore. The UK’s National Health Service Blood and Transplant (NHSBT)unit were able to identify returning travellers through the Rare and Imported Pathogens Laboratory diagnostic testing service. Other sources came through a USA plasmapheresis centre, from the National Institute of Allergy and Infectious Diseases Vaccine Research Centre that is developing a vaccine, from the Caribbean Public Health Agency and also through SAB Biotherapeutics that provided anti-Zika human IgG from immunised transchromosomal cows. This provided enough material for us to launch a multi-centre international collaborative study to identify a candidate reference reagent and the results of that study are described in our paper.
Data analysis showed that a pool of UK NHSBT sera was able to harmonise neutralisation assays using Asian lineage viruses. This material was established as the 1st WHO International Standard in October 2018. In addition, a working reagent is also available through our website (https://www.nibsc.org/products/brm_product_catalogue/sub_category_listing.aspx?category=Vaccines&subcategory=Emerging+Viruses). The latter can be used as an assay performance monitor that may be calibrated to the IS. Publication of this data is intended to alert the scientific community that these materials are available and to promote their adoption and implementation. This will greatly facilitate comparisons of assay data for vaccine development.