Pre-clinical models to define correlates of protection for SARS-CoV-2.

A defined immune profile that predicts protection against a pathogen-of-interest, is referred to as a correlate of protection (CoP). A validated SARS-CoV-2 CoP has yet to be defined, however considerable insights have been provided by pre-clinical vaccine and animal rechallenge studies which have fewer associated limitations than equivalent studies in human vaccinees or convalescents, respectively. This literature review focuses on the advantages of the use of animal models for the definition of CoPs, with particular attention on their application in the search for SARS-CoV-2 CoPs. We address the conditions and interventions required for the identification and validation of a CoP, which are often only made possible with the use of appropriate in vivo models.

Filovirus Neutralising Antibodies: Mechanisms of Action and Therapeutic Application.

Filoviruses, especially Ebola virus, cause sporadic outbreaks of viral haemorrhagic fever with very high case fatality rates in Africa. The 2013-2016 Ebola epidemic in West Africa provided large survivor cohorts spurring a large number of human studies which showed that specific neutralising antibodies played a key role in protection following a natural Ebola virus infection, as part of the overall humoral response and in conjunction with the cellular adaptive response. This review will discuss the studies in survivors and animal models which described protective neutralising antibody response. Their mechanisms of action will be detailed. Furthermore, the importance of neutralising antibodies in antibody-based therapeutics and in vaccine-induced responses will be explained, as well as the strategies to avoid immune escape from neutralising antibodies. Understanding the neutralising antibody response in the context of filoviruses is crucial to furthering our understanding of virus structure and function, in addition to improving current vaccines & antibody-based therapeutics.