Neutralising antibody assays for COVID-19

Rapid high-throughput neutralisation assays are essential for analysis of immune responses in human infection and animal experiments. To enhance access to these assays for COVID-19 research we will establish low-risk, PC2-compliant assays that will be accessible to a larger number of Australian laboratories. These assays can be used to evaluate vaccine candidates and examine antibody responses in clinical trials.

Objective

We will establish low-risk PC2-compliant standardised retroviral pseudo-typing assays that can be performed in PC2 laboratories (as opposed to whole virus work which must be performed in enhanced PC3 labs).

Approach

We will clone the S open reading frame from alphacoronaviruses (229E and NL63), diverse betacoronaviruses from group A (OC43, KHU1), group B including SARS-CoV-1, and a global panel of SARS-CoV-2 isolates (selected for geographical location and sequence evolution of S using GISAID coronavirus resource) and group C (MERS).

Unrelated viral envelopes will be included as controls from HIV-1, HCV and MLV viruses. The assay, performed in 384 well plates (16 viruses in triplicate, 8-point dilution series) will be measured in a Clariostar fitted with a plate stacker (20 plates) allowing high throughput assessment of neutralising antibody (NAb) responses.

Community impact

These assays will have multiple uses including:

• preclinical evaluation of vaccine candidates
• evaluation of the NAb response in human clinical trials
• study of how NAbs develop and their specificity in natural COVID-19 infection.

Once established, we will transfer this technology to 360biolabs who will establish protocols and validation under NATA accreditation. This technology will then be available to Australian and international groups for monitoring immunogenicity in phase I clinical trials of vaccine candidates.