Abstract
The profound consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mandate urgent development of effective vaccines. Here, we evaluated an Amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP modification efficiently delivers CpG to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, immunization with AMP-CpG induced >25-fold higher antigen-specific T cells that produced multiple T helper 1 (TH1) cytokines and trafficked into lung parenchyma. Antibody responses favored TH1 isotypes (IgG2c and IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than natural convalescent patient COVID-19 responses; T cell and antibody responses were maintained despite 10-fold dose reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.
Highlights
The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in worldwide social and economic consequences as well as substantial health care challenges
Recent studies have shown that a subset of patients recover from COVID-19 with SARS-CoV-2–specific T cells but not neutralizing antibodies [6], indicating a potentially important role for T cells as a mechanism of disease prevention or mitigation
Further indication of T cell–mediated disease modification is evident in studies of COVID-19 patient outcomes where lower T cell numbers in patients greater than 60 years of age correlated with increased COVID-19 severity [7]
Summary
The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in worldwide social and economic consequences as well as substantial health care challenges. SARS and Middle East respiratory syndrome (MERS), the more efficient person-to-person transmission and prevalence of asymptomatic infection with SARS-CoV-2 has required public health mitigations including quarantine, contact tracing, face masks, and social distancing to reduce morbidity and mortality. An optimal SARS-CoV-2 vaccine should generate potent T cell immunity alongside neutralizing antibody responses. Optimal SARS-CoV-2 vaccines must produce a T helper 1 (TH1)–biased response since previous SARS [10] and MERS [11] vaccine candidates exacerbated lung disease associated with TH2 responses or as a result of antibody-dependent enhancement of viral entry. An optimal SARS-CoV-2 vaccine must be effective across age groups, especially in the elderly
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