The immunopathogenesis of COVID19 can be depicted as an early viral phase followed by an inflammatory phase. Immune control occurs at various stages (teal arrows), whereas inflammation is important in disease pathogenesis (red arrows). SciencePerspective
). These studies generally support the premise that circulating VN-Ab is a good indicator of protection, not only against severe disease but also against viral replication in the mucosa , thereby reducing transmission. This does not mean that it is circulating antibody that is causing protection: Antibody in the serum does not normally diffuse into mucosal fluids.
With the potential for a disconnection to develop between a COP and the desired effect of future vaccines, such correlates require constant scrutiny and reevaluation. For example, the live attenuated influenza virus vaccine that has been widely adopted for use in children does not induce acceptable concentrations of serum N-Abs. Instead, protective immune responses that have been demonstrated to result from the use of this vaccine require techniques of site-specific mucosal monitoring .
There are clear advantages and pitfalls to the use of correlates and surrogates in diverse medical fields . For example, measuring viral load to determine the effect of antiviral drugs in those living with hepatitis C or HIV is a practical shortcut in tailoring treatment to prevent disease and early death. The relationship between viral suppression and clinical benefit is so clear that there is no need to doubt viral load as a surrogate for long-term benefit.
An accurate and stable COP can save vaccine developers from performing large and expensive trials to demonstrate the efficacy of new or updated vaccines, can predict the effects of established vaccines against new variants of the pathogen, and may expedite regulatory approval of updated or improved vaccines.
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