A WHO International Standard for neutralising antibodies to Chikungunya virus: development and evaluation

Chikungunya fever is a mosquito-borne disease characterised by severe arthralgia and is caused by chikungunya virus (CHIKV), an alphavirus. The aim of this study was to establish a WHO International Standard for CHIKV-specific neutralising antibodies-a potential correlate of protection.

Two candidate International Standards (code numbers 1502/19 and 1504/19) were prepared: 1502/19 using plasma from a CHIKV-convalescent individual and 1504/19 using plasma from blood donors from a CHIKV-endemic region. Potencies of the two candidate International Standards were evaluated alongside samples from recovered individuals and donors previously infected with CHIKV, in an international study (2019-20), using a range of virus-neutralisation assays and immunoassays. Statistical analysis was used to estimate mean and relative potencies of the candidate International Standards. Participants included vaccine developers, arbovirus reference laboratories, and diagnostics manufacturers.

26 laboratories from 12 countries reported detection of anti-CHIKV antibodies and associated potencies. All participants consistently detected both 1502/19 and 1504/19. Overall mean potencies were near-identical for the two candidate International Standards (1502/19, 3·44 log₁₀ and 1504/19, 3·48 log₁₀). Intra-assay variation was considerably lower than inter-assay variation for the candidate International Standards, which varied by more than 100-fold; this variability was seen for all other anti-CHIKV-positive samples. Assay variability was substantially reduced when antibody titres from the panel of samples were expressed relative to 1502/19 or 1504/19. An agreement was reached to establish 1502/19 as the first WHO International Standard for anti-CHIKV neutralising antibodies, with an assigned unitage of 1000 International Unitage/mL.

The use of the candidate International Standards resulted in harmonisation of anti-CHIKV neutralisation titres, allowing for better comparison of results of neutralisation assays for anti-CHIKV antibodies, either as a consequence of natural infection or produced in response to different vaccines, and will be essential in estimating antibody titres associated with protection against CHIKV.

German Ministry of Health (Bundesministerium für Gesundheit).