ABSTRACT
Background: We sought to determine immune and behavioral pre-infection correlates of protection against SARS-CoV-2 post-vaccine infections in a joint analysis of epidemiological and immunological cohort data. Methods: Serum and saliva samples from 176 BNT162b2-vaccinated adults in the Prospective Assessment of SARS-CoV-2 Seroconversion study were collected between October and December 2021 and assessed for serum and saliva levels of Wuhan-1 wild-type (WT) SARS-CoV-2 Spike (S)-specific IgG and IgA binding antibodies (bAb) using a multiplex microsphere-based immunoassay (MMIA). Serum samples were also assessed for WT receptor binding domain (RBD)-specific bAb by two commercial assays, BA.1 S-specific IgG bAb by MMIA, and neutralization activity against D614G, Delta (B.1.617.2), and Omicron BA.1 and BA.1.1 variants using a lentiviral pseudovirus neutralization assay. After the Fall 2021 visit, participants reported all positive PCR and/or antigen tests for SARS-CoV-2. Duration, severity, and type of symptoms, as well as risk exposures and adherence to precautionary measures, were assessed by questionnaires during the Spring 2022 visit. Results: Thirty-two participants (18.2%) developed symptomatic post-vaccination SARS-CoV-2 infections (PVI) between December 7, 2021 and April 1, 2022. Pre-infection WT (geometric mean (GM) of 3,863 vs 2,736 binding antibody unit [BAU]/ml, uninfected vs PVI, p=0.0098) and BA.1 (GM of 276.9 vs 179.9 arbitrary bAb unit [AU]/ml, uninfected vs PVI, p=0.04) anti-S IgG bAb levels measured by MMIA and neutralizing titers (NT) against BA.1 (GM titer [GMT] of 493.6 vs 286.2, uninfected vs PVI, p=0.0313) and BA.1.1 (GMT of 552.0 vs 302.5, uninfected vs PVI, p=0.021) were significantly higher in individuals that did not develop PVIs. WT anti-S bAb levels greater than 5,000 BAU/ml were associated with > 90% protection against symptomatic PVI. In individuals that developed PVI, WT anti-S IgG bAb levels correlated with lower disease severity scores ({rho}= -0.3859, p=0.032) and shorter duration of clinical disease ({rho}= -0.5273, p=0.0023). WT anti-RBD bAb levels measured by commercial assays correlated strongly with bAb levels measured by MMIA ({rho}=0.8239, p<0.0001 and {rho}=0.6929, p<0.0001, Roche and Siemens assays, respectively), but did not reach statistical significance for correlation with protection against PVI. Home risk score, but neither work nor home precautionary measures, correlated strongly with risk of PVI (mean score of 20.77 vs 47.33, uninfected vs PVI respectively, p<0.0001). Conclusions: Anti-S IgG bAb levels (directed against either WT or Omicron BA.1 subvariant) and NTs served as correlates of protection against symptomatic SARS-CoV-2 infection. Anti-S (WT) IgG bAb levels remained a significant correlate of protection against PVIs when adjusting for demography and risk behavior. Results of this study also suggest that commercial assays for anti-S bAb may need to be reformatted to enable detection of higher maximum values for use as predictors of increased susceptibility to SARS-CoV-2 infection.
Subject(s)
Severe Acute Respiratory Syndrome , COVID-19ABSTRACT
Potent cellular responses to viral infections are pivotal for long-lived protection. Evidence is growing that these responses are critical in SARS-CoV-2 immunity. Assessment of a SARS-CoV-2 spike ferritin nanoparticle (SpFN) immunogen paired with two distinct adjuvants, Alhydrogel (AH) or Army Liposome Formulation containing QS-21 (ALFQ) demonstrated unique vaccine evoked immune signatures. SpFN+ALFQ enhanced recruitment of highly activated classical and non-classical antigen presenting cells (APCs) to the vaccine-draining lymph nodes of mice. The multifaceted APC response of SpFN+ALFQ vaccinated mice was associated with an increased frequency of polyfunctional spike-specific T cells with a bias towards TH1 responses and more robust SARS-CoV-2 spike-specific recall response. In addition, SpFN+ALFQ induced Kb spike (539-546)-specific memory CD8+ T cells with effective cytolytic function and distribution to the lungs. This epitope is also present in SARS-CoV, thus suggesting that generation of cross-reactive T cells may provide protection against other coronavirus strains. Our study reveals that a nanoparticle vaccine, combined with a potent adjuvant, generates effective SARS-CoV-2 specific innate and adaptive immune T cell responses that are key components to inducing long-lived immunity.