Correlates of Protection (CoP) are biological parameters present in vaccinated or naturally infected individuals that predict levels of protection against an infectious disease. CoP facilitate vaccine licensing since they enable: a) the selection of antigen composition of a vaccine; b) the assessment of vaccine efficacy in clinical trials without exposure of participants to natural infection; and c) bridging between first- and second-generation vaccines.
Data defining CoP typically derive from: a) pre-clinical and clinical trials; b) passive immunisation studies; c) vaccine breakthrough; d) human challenge studies; e) re-infection cases; and f) immuno-bridging of vaccine efficacy in animals and immunogenicity in humans. However, derivation of CoP for emerging diseases is challenging since by the time new vaccines are urgently needed, immunogenicity and clinical efficacy data are still scarce. Recent epidemics of COVID-19 and Ebola viral disease (EVD) exemplify this.
In the case of COVID-19, regulatory authorities licenced ‘Emergency Use’ vaccines after Phase III clinical trials were conducted. Abundant data from these trials and from post-licensure studies established a correlation between different immunological parameters and protection. Virus neutralising antibody (VNAb) levels predicted, reasonably likely, the degree of protection against SARSCoV-2 infection and disease. However, to date, an internationally standardised threshold of protection remains elusive and the emergence of SARS-CoV-2 variants with different clinical and antigenic properties to the ancestral Wuhan virus complicate the problem. Furthermore, data indicating that other mechanisms of adaptive immunity are likely involved in protection continuously emerge.
Searching CoP for EVD presents additional challenges. The 2013-2016 West Africa epidemic accelerated vaccine development. However, unlike COVID-19, EVD was not globally widespread and the opportunities for evaluating vaccine efficacy under natural exposure conditions were very limited. Specific clinical trial designs enabled the assessment of efficacy in the middle of an on-going outbreak and thresholds of VNAb that correlated with protection were defined. However, additional clinical data to validate these determinations is difficult to obtain because Ebola outbreaks have been sporadic since 2016, and endemic countries remain largely unvaccinated.
Furthermore, many different technologies (i.e., nucleic acid, sub-unit, viral vector vaccines) are currently used for developing vaccines against emerging diseases. However, it remains to be elucidated whether a CoP for a particular disease can be universally applied to all vaccine platforms.
The derivation of CoP for emerging diseases is a subject of intense research and debate. Further work is needed to define CoP for COVID-19 and Ebola and to develop common approaches for defining CoP for any emerging disease.
On this Research Topic we aim to highlight new research findings on EVD, Covid-19 and other emerging virus diseases that have an impact on defining CoP. We invite colleagues working on immunology, virology, vaccinology, biostatistics, and epidemiology of emerging diseases of high priority (https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts) to submit original research articles or reviews on any aspect concerning CoP including:
- Immune mechanisms of protection
- Vaccine efficacy
- Pre-clinical studies
- Immuno-bridging
- Regulatory and licensing
- Manufacturing
- Clinical trial design
- Assay standardisation
Correlates of Protection (CoP) are biological parameters present in vaccinated or naturally infected individuals that predict levels of protection against an infectious disease. CoP facilitate vaccine licensing since they enable: a) the selection of antigen composition of a vaccine; b) the assessment of vaccine efficacy in clinical trials without exposure of participants to natural infection; and c) bridging between first- and second-generation vaccines.
Data defining CoP typically derive from: a) pre-clinical and clinical trials; b) passive immunisation studies; c) vaccine breakthrough; d) human challenge studies; e) re-infection cases; and f) immuno-bridging of vaccine efficacy in animals and immunogenicity in humans. However, derivation of CoP for emerging diseases is challenging since by the time new vaccines are urgently needed, immunogenicity and clinical efficacy data are still scarce. Recent epidemics of COVID-19 and Ebola viral disease (EVD) exemplify this.
In the case of COVID-19, regulatory authorities licenced ‘Emergency Use’ vaccines after Phase III clinical trials were conducted. Abundant data from these trials and from post-licensure studies established a correlation between different immunological parameters and protection. Virus neutralising antibody (VNAb) levels predicted, reasonably likely, the degree of protection against SARSCoV-2 infection and disease. However, to date, an internationally standardised threshold of protection remains elusive and the emergence of SARS-CoV-2 variants with different clinical and antigenic properties to the ancestral Wuhan virus complicate the problem. Furthermore, data indicating that other mechanisms of adaptive immunity are likely involved in protection continuously emerge.
Searching CoP for EVD presents additional challenges. The 2013-2016 West Africa epidemic accelerated vaccine development. However, unlike COVID-19, EVD was not globally widespread and the opportunities for evaluating vaccine efficacy under natural exposure conditions were very limited. Specific clinical trial designs enabled the assessment of efficacy in the middle of an on-going outbreak and thresholds of VNAb that correlated with protection were defined. However, additional clinical data to validate these determinations is difficult to obtain because Ebola outbreaks have been sporadic since 2016, and endemic countries remain largely unvaccinated.
Furthermore, many different technologies (i.e., nucleic acid, sub-unit, viral vector vaccines) are currently used for developing vaccines against emerging diseases. However, it remains to be elucidated whether a CoP for a particular disease can be universally applied to all vaccine platforms.
The derivation of CoP for emerging diseases is a subject of intense research and debate. Further work is needed to define CoP for COVID-19 and Ebola and to develop common approaches for defining CoP for any emerging disease.
On this Research Topic we aim to highlight new research findings on EVD, Covid-19 and other emerging virus diseases that have an impact on defining CoP. We invite colleagues working on immunology, virology, vaccinology, biostatistics, and epidemiology of emerging diseases of high priority (https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts) to submit original research articles or reviews on any aspect concerning CoP including:
- Immune mechanisms of protection
- Vaccine efficacy
- Pre-clinical studies
- Immuno-bridging
- Regulatory and licensing
- Manufacturing
- Clinical trial design
- Assay standardisation