Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

RFC7631: TLV Naming in the Mobile Ad Hoc Network (MANET) Generalized Packet/Message Format

This document reorganizes the naming of already-allocated TLV (typelength-value) types and type extensions in the "Mobile Ad hoc NETwork (MANET) Parameters" registries defined by RFC 5444 to use names appropriately. It has no consequences in terms of any protocol implementation. This document also updates the Expert Review guidelines in RFC 5444, so as to establish a policy for consistent naming of future TLV type and type extension allocations. It makes no other changes to RFC 5444. Status of This Memo This is an Internet Standards Track document. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Further information on Internet Standards is available in Section 2 of RFC 5741. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained at http://www.rfc-editor.org/info/rfc7631

RFC7188: Optimized Link State Routing Protocol Version 2 (OLSRv2) and MANET Neighborhood Discovery Protocol (NHDP) Extension TLVs

This specification describes extensions to definitions of TLVs used by the Optimized Link State Routing Protocol version 2 (OLSRv2) and the MANET Neighborhood Discovery Protocol (NHDP) to increase their abilities to accommodate protocol extensions. This document updates RFC 7181 (OLSRv2) and RFC 6130 (NHDP). Status of This Memo This is an Internet Standards Track document. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Further information on Internet Standards is available in Section 2 of RFC 5741. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained at http://www.rfc-editor.org/info/rfc7188

RFC7466: An Optimization for the Mobile Ad Hoc Network (MANET) Neighborhood Discovery Protocol (NHDP)

The link quality mechanism of the Mobile Ad Hoc Network (MANET) Neighborhood Discovery Protocol (NHDP) enables "ignoring" some 1-hop neighbors if the measured link quality from that 1-hop neighbor is below an acceptable threshold while still retaining the corresponding link information as acquired from the HELLO message exchange. This allows immediate reinstatement of the 1-hop neighbor if the link quality later improves sufficiently

RFC7187: Routing Multipoint Relay Optimization for the Optimized Link State Routing Protocol Version 2 (OLSRv2)

This specification updates the Optimized Link State Routing Protocol version 2 (OLSRv2) with an optimization to improve the selection of routing multipoint relays. The optimization retains full interoperability between implementations of OLSRv2 with and without this optimization. Status of This Memo This is an Internet Standards Track document. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Further information on Internet Standards is available in Section 2 of RFC 5741. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained at http://www.rfc-editor.org/info/rfc7187

RFC7722: Multi-Topology Extension for the Optimized Link State Routing Protocol Version 2 (OLSRv2)

This specification describes an extension to the Optimized Link State Routing Protocol version 2 (OLSRv2) to support multiple routing topologies, while retaining interoperability with OLSRv2 routers that do not implement this extension. This specification updates RFCs 7188 and 7631 by modifying and extending TLV registries and descriptions. Status of This Memo This document is not an Internet Standards Track specification; it is published for examination, experimental implementation, and evaluation. This document defines an Experimental Protocol for the Internet community. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Not all documents approved by the IESG are a candidate for any level of Internet Standard; see Section 2 of RFC 5741. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained at http://www.rfc-editor.org/info/rfc7722

RFC7182: Integrity Check Value and Timestamp TLV Definitions for Mobile Ad Hoc Networks (MANETs)

This document revises, extends, and replaces RFC 6622. It describes general and flexible TLVs for representing cryptographic Integrity Check Values (ICVs) and timestamps, using the generalized Mobile Ad Hoc Network (MANET) packet/message format defined in RFC 5444. It defines two Packet TLVs, two Message TLVs, and two Address Block TLVs for affixing ICVs and timestamps to a packet, a message, and one or more addresses, respectively. Status of This Memo This is an Internet Standards Track document. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Further information on Internet Standards is available in Section 2 of RFC 5741

RFC7185: Rationale for the Use of Link Metrics in the Optimized Link State Routing Protocol Version 2 (OLSRv2)

The Optimized Link State Routing Protocol version 2 (OLSRv2) includes the ability to assign metrics to links and to use those metrics to allow routing by other than minimum hop count routes. This document provides a historic record of the rationale for, and design considerations behind, how link metrics were included in OLSRv2. Status of This Memo This document is not an Internet Standards Track specification; it is published for informational purposes. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Not all documents approved by the IESG are a candidate for any level of Internet Standard; see Section 2 of RFC 5741. Information about the current status of this document, any errata, and how to provide feedback on it may be obtained at http://www.rfc-editor.org/info/rfc7185

RFC7183: Integrity Protection for the Neighborhood Discovery Protocol (NHDP) and Optimized Link State Routing Protocol Version 2 (OLSRv2

The mechanism in this specification can also be used for other protocols that use the generalized packet/message format described in RFC 5444. This document updates RFC 6130 and RFC 7181 by mandating the implementation of this integrity and replay protection in NHDP and OLSRv2. Status of This Memo This is an Internet Standards Track document. This document is a product of the Internet Engineering Task Force (IETF). It represents the consensus of the IETF community. It has received public review and has been approved for publication by the Internet Engineering Steering Group (IESG). Further information on Internet Standards is available in Section 2 of RFC 5741