Table 2.

Data purpose matrix for correlates of protection data (disease agnostic)

	Vaccine objective
	Clinical development	Regulatory and licensure	Vaccine policy and introduction
Key stakeholder/audience User of the CoP data	Clinicians Epidemiologists, microbiologists, immunologists Statisticians Manufacturers/Developers (pharma and biotech, PPPs) Funders and donors Consortium members	NRAs and Regional Regulatory Authorities WHO Vaccines Pre-Q Manufactures/Developers (pharma and biotech, PPPs) Funders and donors	WHO, SAGE, GNN RITAGs NITAGs Ministries of Health/Finance Industry/manufacturers
Data purpose: What do the stakeholders use the CoP data for? What decisions are made using the CoP data?	Identify correct/best choice of vaccine antigen based on pathogen biology Confirm lot-to-lot consistency Confirm lack of interference in concomitant use Provide early insight into efficacy Enable design of go/no-go criteria for Ph1 to determine progress to Ph2 De-risk or down-size phase 3, Extend indication through the use of immunobridging to expand label claims e.g. into additional age groups, Validate success of tech transfer Inform formulation, schedule and dose. To establish biomarkers for Immunobridging.	Immunobridging of a new product by comparing immune responses to a licenced comparator to infer effectiveness in: - Different age groups or demographic groups, - Change of dose, regimen or need for boosters - Change in formulation - Bridge manufacturing changes - Establish lack of interference in concomitant vaccine use Inclusion of additional strains to a licenced product without efficacy data Essential part of data package where efficacy studies are not ethical or feasible Definition of endpoints for phase IV evaluation if required.	To reduce delays in vaccine introduction by establishing immunogenicity in local populations where direct efficacy data are not available. Inform design of phase 4 studies to gather safety and effectiveness data in local populations and link to immunogenicity (and validate correlate). Prioritising limited vaccine stocks to key target groups Refining dosing or boosting regime Determine susceptibility of population to disease where a threshold is established. duction
Requirements for the use of CoP data Data requirements: What data, from where/when (disease- or endpoint specific) Properties of data: What do the stakeholders need to use CoP data with confidence as part of a data package	Consistent sampling collection and processing methods (especially for mucosal immunity) Availability of accurate, standardised, validated assays including: agreement on performance criteria (QC), endpoints, and where non-functional assays would be acceptable Specific T cell assays (cheaper and more easily standardised) using standardised reagents. Globally used & validated standards – ideally international standards - and reagents e.g. common source of antigen Framework for assessing quality of data and evidence Standardised and validated analysis methods inc. statistical plans “Breadth” studies to see suitability of CoP across serotypes and populations	Consistent use of assays, reagents, and standardised procedures to produce reliable and comparable immunogenicity data. Clarity and consensus on definition and use of CoP/ immune biomarkers between regulators, especially in immunobridging. Well-designed dose-ranging studies Framework for assessing quality of CoP data and evidence Coordination to enable inter-regulatory reliance through transparency Consistent documentation	Post-licensure studies to assess durability and effectiveness of CoP in different populations Data from multiple clinical trial sites to give confidence that CoP reflects immune responses of where vaccine will be used Alignment with regulators on what constitutes sufficient “protection” data Guidance from SAGE Communication and co-ordination with regulators and developers to clarify data needs for decision-making. Guidance needed on when it is appropriate to use CoP data for an intended purpose, and what evidence requirements are.

NRA National regulatory authority, SAGE Scientific Advisory Group of Experts, GNN Global NITAG network, RITAG Regional Immunisation Technical Advisory Group, NITAG National Immunisation Technical Advisory Group.