A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2 (preprint)

As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laboratory-based testing. Current rapid point-of-care (POC) tests measure antibodies (Ab) against the SARS-CoV-2 virus, however, these tests provide no information on whether the antibodies can neutralise virus infectivity and are potentially protective, especially against newly emerging variants of the virus. Neutralising Antibodies (NAb) are emerging as a strong correlate of protection, but most current NAb assays require many hours or days, samples of venous blood, and access to laboratory facilities, which is especially problematic in resource-limited settings. We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibodies from whole blood, with a result that can be determined by eye (semi-quantitative) or on a small instrument (quantitative), and results show high correlation with microneutralisation assays. This assay also provides a measure of total anti-RBD antibody, thereby providing evidence of exposure to SARS-CoV-2 or immunisation, regardless of whether NAb are present in the sample. By testing samples from immunised macaques, we demonstrate that this test is equally applicable for use with animal samples, and we show that this assay is readily adaptable to test for immunity to newly emerging SARS-CoV-2 variants. Lastly, using a cohort of vaccinated humans, we demonstrate that our whole-blood test correlates closely with microneutralisation assay data (R 2 =0.75, p<0.0001), and that fingerprick whole blood samples are sufficient for this test. Accordingly, the COVID-19 NAb-test™ device described here can provide a rapid readout of immunity to SARS-CoV-2 at the point of care.

Reanalysis of the Pfizer mRNA BNT162b2 SARS-CoV-2 vaccine data fails to find any increased efficacy following the boost: Implications for vaccination policy and our understanding of the mode of action (preprint)

Background In clinical trials two vaccinations with mRNA vaccines have shown high efficacy in preventing COVID-19. However, in the context of a pandemic, the time to generation of protective immunity, the need for and timing of a second vaccination are matters of legitimate debate. This manuscript explores the efficacy and timing of the second dose COVID-19 vaccines, including a reanalysis of data from the Pfizer mRNA BNT162b2 mRNA SARS-CoV-2 vaccine phase 3 study. Methods and findings A non-weighted three-segment, two knot linear regression was fitted to the published cumulative infection incidence from the Pfizer BNT162b2 vaccine Phase III trial using the lspine routine in R. The optimal knot days were estimated through sensitivity analysis and the confidence limits for efficacy estimates were determined by Monte Carlo Simulations. This analysis showed the vaccine was effective from day 11 post first vaccination. The estimated efficacy over the period 11 to 28 days post first vaccination was 0.94 and there was no detectable increase in efficacy following the second vaccination. The efficacy post first vaccination substantially preceded the development of detectable serum neutralizing antibody. Conclusions Strongly protective immunity develops rapidly following a single vaccination and at least in the short period covered by the timetable of the Phase III trial, there was no additional benefit from a second vaccination. This increases options for use of this vaccine, e.g., for ring fence vaccination, for use in travelers and for mass vaccination rollout. It highlights the need for further research into duration of immunity following a single vaccination and for understanding mechanisms of protection.