A Precision Adjuvant Approach to Enhance Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccines Optimized for Immunologically Distinct Vulnerable Populations

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused significant mortality, especially among older adults whose distinct immune system reflects immunosenescence. Multiple SARS-CoV-2 vaccines have received emergency use authorization and/or licensure from the US Food and Drug Administration and throughout the world. However, their deployment has heighted significant limitations, such by age-dependent immunogenicity, requirements for multiple vaccine doses, refrigeration infrastructure that is not universally available, as well as waning immunity. Thus, there was, and continues to be a need for continued innovation during the pandemic given the desire for dose-sparing, formulations stable at more readily achievable temperatures, need for robust immunogenicity in vulnerable populations, and development of safe and effective pediatric vaccines. In this context, optimal SARS-CoV-2 vaccines may ultimately rely on inclusion of adjuvants as they can potentially enhance protection of vulnerable populations and provide dose-sparing effects enabling single shot protection.

Keywords: COVID-19; SARS-CoV-2; adjuvants; precision vaccines; vulnerable populations.

Figure 1.

COVID-19 hospitalization and death by age in unvaccinated populations. Early in the COVID-19 pandemic, increasing age was identified as the number 1 risk factor for developing hospitalization and death following SARS-CoV-2 infection. Abbreviations: COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Data: https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-age.html.

Figure 2.

A comprehensive multidisciplinary approach to defining precision adjuvants for a coronavirus vaccine active in older adults. Traditional vaccine development can lead to sub-optimal vaccine efficacy outcomes, normally attributed to an overreliance on nonhuman species-models and underappreciated value of incorporating age-specificity readout into the preclinical vaccine development pipeline. An alternative precision vaccine approach aims to accelerate development of optimal vaccine approaches, increasing the probably the final formulations will better protect the most vulnerable by (a) defining a very broad adjuvant pipeline, (b) rapidly screening adjuvants for activity toward human elderly PBMCs, and (c) combining lead adjuvants with multiple SARS-CoV-2 antigens. Lead adjuvanted vaccines are then advanced to age-specific animal studies and beyond. Abbreviations: PBMC, peripheral blood mononuclear cell; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.