Abstract
Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The emergence of C.1.2, associated with a high substitution rate, includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 VOC/VOIs. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta showed high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
The Network for Genomic Surveillance South Africa (NGS-SA) is supported by the Strategic Health Innovation Partnerships Unit of the South African Medical Research Council, with funds received from the South African Department of Science and Innovation. Sequencing activities for the different sequencing hubs were provided by a conditional grant from the South African National Department of Health as part of the emergency COVID-19 response, a cooperative agreement between the National Institute for Communicable Diseases of the National Health Laboratory Service and the United States Centers for Disease Control and Prevention (grant number 5 U01IP001048-05-00); the African Society of Laboratory Medicine (ASLM) and Africa Centers for Disease Control and Prevention through a sub-award from the Bill and Melinda Gates Foundation grant number INV-018978; the UK Foreign, Commonwealth and Development Office and Wellcome (Grant no 221003/Z/20/Z); the South African Medical Research Council (Reference number SHIPNCD 76756); the Department of Health and Social Care and managed by the Fleming Fund and performed under the auspices of the SEQAFRICA project; German Federal Ministry of Education and Research (BMBF; grant number 01KA1606; and G7 collaboration grant with the Robert Koch Institute for COVID19) for the African Network for Improved Diagnostics, Epidemiology and Management of common infectious Agents (ANDEMIA). Hyrax Biosciences Exatype platform was supported by the South African Medical Research Council with funds received from the Department of Science and Innovation. The content and findings reported/illustrated are the sole deduction, view and responsibility of the researcher and do not reflect the official position and sentiments of the SAMRC or the Department of Science and Innovation. This study was supported by the Bill and Melinda Gates award INV-018944 (AS), National Institutes of Health award R01 AI138546 (AS), South African Medical Research Council awards (AS, TdO, PLM) and National Institutes of Health U01 AI151698 for the United World Antivirus Research Network (UWARN) (WVV). SIR is a LOreal/UNESCO Women in Science South African Young Talents awardee. DPM and CW were supported by the Wellcome Trust (222574/Z/21/Z). CW and JB are funded by the EDCTP (RADIATES Consortium; RIA2020EF-3030). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the NRF (Grant No 98341) and the Strategic Health Innovations Program of the SA MRC.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
The project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC) (ref. M180832, M210159, M210752), University of KwaZulu Natal Biomedical Research Ethics Committee (ref. BREC/00001510/2020), Stellenbosch University HREC (ref. N20/04/008_COVID19) and the University of Cape Town HREC (ref. 383/2020) and the University of Pretoria, Faculty of Health human ethics committee, (ref H101 2017). Individual participant consent was not required for the genomic surveillance. This requirement was waived by the Research Ethics Committees. Ethics for the Steve Biko Cohort was approved by the University of Pretoria, Human Research Ethics Committee (Medical) (247/2020). Ethics for the Groote Schuur Hospital was approved by the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town (R021/2020). Ethics for the AZD1222/ChAdOX1 nCOV19 vaccine trial was given approval from the Pan African Clinical Trials Registry (PACTR202006922165132) as well as the South Africa Health Products Regulatory Authority (SAHPRA: 20200407). Ethics approval for the use of the Janssen/Johnson and Johnson Ad26.COV2.S samples were obtained from the Human Research Ethics Committee of the Faculty of Health Sciences, University of the Witwatersrand (M210465). Ethics approval for the use of Pfizer/BioNTech BNT162b2 samples were obtained from the Human Research Ethics Committee of the Faculty of Health Sciences, University of the Witwatersrand (M210465) and approval for the use of these samples was obtained by the Biomedical Research Ethics Committee at the University of KwaZulu Natal (BREC/00001275/2020).
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Footnotes
↵# joint first authors
This version of the paper now includes phenotypic data associated with the C.1.2 lineage involving neutralization and ADCC activity in vaccine and convalescent plasma. As a result we have also included additional authors responsible for sample collection and running of the phenotypic data. The sequencing data has also been updated to include recent samples.
Data Availability
All SARS-CoV-2 assemblies used in this analysis are deposited in GISAID (https://www.gisaid.org/)20,21 and the GISAID accessions are provided in Supplementary Tables 1 and 2. The Nextstrain build of C.1.2 and global sequences will be made available at https://nextstrain.org/groups/ngs-sa.
