Immune correlates of protection for SARS-CoV-2, Ebola and Nipah virus infection

Abstract

Correlates of protection (CoP) are biological parameters that predict a certain level of protection against an infectious disease. Well-established correlates of protection facilitate the development and licensing of vaccines by assessing protective efficacy without the need to expose clinical trial participants to the infectious agent against which the vaccine aims to protect. Despite the fact that viruses have many features in common, correlates of protection can vary considerably amongst the same virus family and even amongst a same virus depending on the infection phase that is under consideration. Moreover, the complex interplay between the various immune cell populations that interact during infection and the high degree of genetic variation of certain pathogens, renders the identification of immune correlates of protection difficult. Some emerging and re-emerging viruses of high consequence for public health such as SARS-CoV-2, Nipah virus (NiV) and Ebola virus (EBOV) are especially challenging with regards to the identification of CoP since these pathogens have been shown to dysregulate the immune response during infection. Whereas, virus neutralising antibodies and polyfunctional T-cell responses have been shown to correlate with certain levels of protection against SARS-CoV-2, EBOV and NiV, other effector mechanisms of immunity play important roles in shaping the immune response against these pathogens, which in turn might serve as alternative correlates of protection. This review describes the different components of the adaptive and innate immune system that are activated during SARS-CoV-2, EBOV and NiV infections and that may contribute to protection and virus clearance. Overall, we highlight the immune signatures that are associated with protection against these pathogens in humans and could be used as CoP.

Keywords: Ebola virus; Nipah virus; SARS-CoV-2; cell-mediated immunity; emerging viruses; humoral immunity; immune correlates of protection.

Figure 1

Innate, humoral and cellular-mediated immune responses. The main cellular immune players of the cell-mediated innate (green background, top left), humoral (purple, top right) and adaptative cell-mediated (blue, bottom) immune responses and their interconnections are displayed. The components of the innate immune system provide, together with their effector functions and soluble mediators, an immediate response to pathogens. This response triggers in turn the adaptive immune system, mostly T cell-mediated immune responses that lead to the activation of effector T cells and the activation of B cell functions. This branch of immunity provides specific, long-lasting immune responses. The adaptive and innate immune systems are connected; importantly, while soluble mediators are important to link both arms of immunity, the presentation of foreign peptides (in green) by Antigen Presenting Cells (APCs) is also necessary, together with immune mediators such as cytokines (CK). This figure was created with smart.servier.com.