Further antibody escape by Omicron BA.4 and BA.5 from vaccine and BA.1 serum (preprint)

The Omicron lineage of SARS-CoV-2, first described in November 2021, spread rapidly to become globally dominant and has split into a number of sub-lineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa's Gauteng region uncovered two new sub-lineages, BA.4 and BA.5 which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences and, although closely related to BA.2, contain further mutations in the receptor binding domain of spike. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by serum from triple AstraZeneca or Pfizer vaccinated individuals compared to BA.1 and BA.2. Furthermore, using serum from BA.1 vaccine breakthrough infections there are likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status (preprint)

Background Natural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. Methods In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing. Results 13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI <0.01-0.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [0.02-0.38]) and 85% (0.15 [0.08-0.26]) respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [0.21-0.52]) and any PCR-positive result by 64% (0.36 [0.26-0.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7. Conclusion Natural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.

Antibodies to SARS-CoV-2 are associated with protection against reinfection (preprint)

BackgroundIt is critical to understand whether infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) protects from subsequent reinfection. MethodsWe investigated the incidence of SARS-CoV-2 PCR-positive results in seropositive and seronegative healthcare workers (HCWs) attending asymptomatic and symptomatic staff testing at Oxford University Hospitals, UK. Baseline antibody status was determined using anti-spike and/or anti-nucleocapsid IgG assays and staff followed for up to 30 weeks. We used Poisson regression to estimate the relative incidence of PCR-positive results and new symptomatic infection by antibody status, accounting for age, gender and changes in incidence over time. ResultsA total of 12219 HCWs participated and had anti-spike IgG measured, 11052 were followed up after negative and 1246 after positive antibody results including 79 who seroconverted during follow up. 89 PCR-confirmed symptomatic infections occurred in seronegative individuals (0.46 cases per 10,000 days at risk) and no symptomatic infections in those with anti-spike antibodies. Additionally, 76 (0.40/10,000 days at risk) anti-spike IgG seronegative individuals had PCR-positive tests in asymptomatic screening, compared to 3 (0.21/10,000 days at risk) seropositive individuals. Overall, positive baseline anti-spike antibodies were associated with lower rates of PCR-positivity (with or without symptoms) (adjusted rate ratio 0.24 [95%CI 0.08-0.76, p=0.015]). Rate ratios were similar using anti-nucleocapsid IgG alone or combined with anti-spike IgG to determine baseline status. ConclusionsPrior SARS-CoV-2 infection that generated antibody responses offered protection from reinfection for most people in the six months following infection. Further work is required to determine the long-term duration and correlates of post-infection immunity.