Parsing chronological and biological age effects on vaccine responses

Abstract

As illustrated by the COVID-19 pandemic, older age, particularly when accompanied by common chronic illnesses of aging, is arguably the most significant population attributable factor for severe outcomes of acute respiratory infection, including the risk of hospitalization, disability and death. In the absence of widely available and highly effective treatments, vaccines remain our most powerful tool to help overcome this vulnerability through the prevention of primary infection, and far more importantly, by improving clinical outcomes once infection does take place. In the case of SARS-CoV-2, vaccine effectiveness (VE) against hospitalization was remarkable for dominant strains prior to omicron, whereas for influenza or Streptococcus pneumoniae VE ranges from 80% to <10%, depending on the season and infecting strain/serotype. Nonetheless, for all three pathogens VE decreases with age, which is caused by deficiencies in the capacity of older adults’ immune systems to mount productive and persistent antibody and/or cell-mediated responses to the vaccine [1]. Given that extremely large, costly and typically lengthy clinical trials are often required to estimate VE reliably, the vast majority of human vaccine studies assess immune correlates of protection as a proxy to VE. For these studies, antibody-related parameters such as neutralization capacity are most commonly employed since they are generally simpler from a technical standpoint and many have been rigorously standardized.