ABSTRACT
The emergence of SARS-CoV-2 Omicron, first identified in Botswana and South Africa, may compromise vaccine effectiveness and the ability of antibodies triggered by previous infection to protect against re-infection (1). Here we investigated whether Omicron escapes antibody neutralization in South Africans, either previously SARS-CoV-2 infected or uninfected, who were vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa and compared plasma neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation, observing that Omicron still required ACE2 to infect. For neutralization, blood samples were taken soon after vaccination, so that vaccine elicited neutralization was close to peak. Neutralization capacity of the D614G virus was much higher in infected and vaccinated versus vaccinated only participants but both groups had 22-fold Omicron escape from vaccine elicited neutralization. Previously infected and vaccinated individuals had residual neutralization predicted to confer 73% protection from symptomatic Omicron infection, while those without previous infection were predicted to retain only about 35%. Both groups were predicted to have substantial protection from severe disease. These data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly boosting, could maintain reasonable effectiveness against Omicron. A waning neutralization response is likely to decrease vaccine effectiveness below these estimates. However, since protection from severe disease requires lower neutralization levels and involves T cell immunity, such protection may be maintained.
ABSTRACT
BackgroundPeople living with HIV (PLWH) have been reported to have an increased risk of more severe COVID-19 disease outcome and an increased risk of death relative to HIV-uninfected individuals. Here we assessed the ability of the Johnson and Johnson Ad26.CoV2.S vaccine to elicit neutralizing antibodies to the Delta variant in PLWH relative to HIV-uninfected individuals. We also compared the neutralization after vaccination to neutralization elicited by SARS-CoV-2 infection only in HIV-uninfected, suppressed HIV PLWH, and PLWH with detectable HIV viremia. MethodsWe enrolled 26 PLWH and 73 HIV-uninfected participants from the SISONKE phase 3b open label South African clinical trial of the Ad26.CoV2.S vaccine in health care workers (HCW). Enrollment was a median 56 days (range 19-98 days) post-vaccination and PLWH in this group had well controlled HIV infection. We also enrolled unvaccinated participants previously infected with SARS-CoV-2. This group consisted of 34 PLWH and 28 HIV-uninfected individuals. 10 of the 34 (29%) SARS-CoV-2 infected only PLWH had detectable HIV viremia. We used records of a positive SARS-CoV-2 qPCR result, or when a positive result was absent, testing for SARS-CoV-2 nucleocapsid antibodies, to determine which vaccinated participants were SARS-CoV-2 infected prior to vaccination. Neutralization capacity was assessed using participant plasma in a live virus neutralization assay of the Delta SARS-CoV-2 variant currently dominating infections in South Africa. This study was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal (reference BREC/00001275/2020). FindingsThe majority (68%) of Ad26.CoV2.S vaccinated HCW were found to be previously infected with SARS-CoV-2. In this group, Delta variant neutralization was 9-fold higher compared to the infected only group (GMT=306 versus 36, p<0.0001) and 26-fold higher relative to the vaccinated only group (GMT=12, p<0.0001). No significant difference in Delta variant neutralization capacity was observed in vaccinated and previously SARS-CoV-2 infected PLWH relative to vaccinated and previously SARS-CoV-2 infected, HIV-uninfected participants (GMT=307 for HIV-uninfected, 300 for PLWH, p=0.95). SARS-CoV-2 infected, unvaccinated PLWH showed 7-fold reduced neutralization of the Delta variant relative to HIV-uninfected participants (GMT=105 for HIV-uninfected, 15 for PLWH, p=0.001). There was a higher frequency of non-responders in PLWH relative to HIV-uninfected participants in the SARS-CoV-2 infected unvaccinated group (27% versus 0%, p=0.0029) and 60% of HIV viremic versus 13% of HIV suppressed PLWH were non-responders (p=0.0088). In contrast, the frequency of non-responders was low in the vaccinated/infected group, and similar between HIV-uninfected and PLWH. Vaccinated only participants showed a low neutralization of the Delta variant, with a stronger response in PLWH (GMT=6 for HIV-uninfected, 73 for PLWH, p=0.02). InterpretationThe neutralization response of the Delta variant following Ad26.CoV2.S vaccination in PLWH with well controlled HIV was not inferior to HIV-uninfected study participants. In SARS-CoV-2 infected and non-vaccinated participants, the presence of HIV infection reduced the neutralization response to SARS-CoV-2 infection, and this effect was strongest in PLWH with detectable HIV viremia FundingSouth African Medical Research Council, The Bill & Melinda Gates Foundation.
ABSTRACT
Following the COVID-19 pandemic outbreak in late 2019, a large number of antibody tests were developed for use in seroprevalence studies aimed at determining the extent of current or previous SARS-CoV-2 virus infections in a given population. The vast majority of these tests are qualitative and use a single target for antibody detection, incorporating either full-length or truncated versions of the nucleocapsid (N) or spike (S) proteins from SARS-CoV-2. Importantly, mono-epitope tests - whether qualitative or quantitative - are unable to localise antibody binding or characterise the distribution and titres of epitope recognition by anti-SARS-CoV-2 antibodies within an individual or across a population. However, it seems plausible that if such information were available, it may correlate with the presence of potent, high-titre, neutralising antibodies that afford protection again imminent re-infection, as well as with the likelihood of developing a memory B-cell response that would provide more durable protection. We have developed a novel, quantitative, multi-antigen, multiplexed, array-based immunoassay platform, ImmuSAFE COVID+ (ImmuSAFE) comprising 6 functionally validated domains or regions of the N protein of SARS-CoV-2 expressed using Sengenics KREX technology. This array platform enables determination of both the position and breadth of anti-SARS-CoV-2 antibody responses following natural infection or vaccination. To validate our platform, 100 serum samples (confirmed sero-positive COVID-19 cases, n=50; pre-pandemic HIV positive controls, n=50) were tested for IgG seropositivity to the N antigen, yielding 100% specificity and 100% sensitivity. All 50 cases showed positive antibody reactivity towards at least one N protein epitope, whilst all 50 controls showed antibody reactivity below threshold values. Broad variation was also observed in the magnitude and breadth of antibodies present, represented as an Epitope Coverage score (EPC). A positive correlation was observed between increasing age and EPC values, with individuals under 40 years old having a mean EPC score of 3.1, whilst individuals above the age of 60 had a mean EPC of 5.1. This finding may have broad implications for the natural history of COVID-19 disease in different individuals.
