ABSTRACT
Emerging of SARS-CoV-2 variants and waning of vaccine/infection-induced immunity poses threats to curbing the COVID-19 pandemic. An effective, safe, and convenient booster vaccine will be needed. We hypothesized that a variant-modified mucosal booster vaccine might induce local immunity to prevent SARS-CoV-2 infection at the port of entry. The beta-variant is hardest to cross-neutralize. Herein we assessed the protective efficacy of an intranasal booster composed of beta variant-spike protein S1 with IL-15 and TLR agonists in previously immunized macaques. The macaques were first vaccinated with Wuhan strain S1 with the same adjuvant. One year later, negligibly detectable SARS-CoV-2-specific antibody remained. Nevertheless, the booster induced vigorous humoral immunity including serum- and bronchoalveolar lavage (BAL)-IgG, secretory nasal- and BAL-IgA, and neutralizing antibody against the original strain and/or beta variant. Beta-variant S1-specific CD4+ and CD8+ T cell responses were also elicited in PBMC and BAL. Following SARS-CoV-2 beta variant challenge, the vaccinated group demonstrated significant protection against viral replication in the upper and lower respiratory tracts, with almost full protection in the nasal cavity. The fact that one intranasal beta-variant booster administrated one year after the first vaccination provoked protective immunity against beta variant infections may inform future SARS-CoV-2 booster design and administration timing.
Subject(s)
COVID-19ABSTRACT
Background: Durability of SARS-CoV-2 Spike antibody responses after infection provides information relevant to understanding protection against COVID-19 in humans. We report the results of a follow-up evaluation of anti-SARS-CoV-2 antibodies in 23 convalescent patients with a median follow-up of 14 months (range 12.4-15.4) post first symptom onset.Findings: We found persistence of antibodies for all four specificities tested [Spike, Spike Receptor Binding Domain (Spike-RBD), Nucleocapsid, Nucleocapsid RNA Binding Domain (N-RBD)]. Anti-Spike antibodies persist at higher levels than anti-Nucleocapsid antibodies. The durability analysis supports a bi-phasic antibody decay with longer half-lives of antibodies after 6 months and antibody persistence for up to 14 months. Patients infected with the Wuhan (WA1) strain maintained strong cross-reactive recognition of Alpha and Delta Spike-RBD but significantly reduced binding to Beta and Mu Spike-RBD. Sixty percent of convalescent patients with detectable WA1-specific NAb also showed strong neutralization of the Delta variant. These data show that convalescent patients maintain functional antibody responses for more than one year after infection. One patient from this cohort showed strong increase of both Spike and Nucleocapsid antibodies at 14 months postinfection with robust cross-reactive antibodies and neutralization of a panel of Spike variants including Beta and Gamma, suggesting SARS-CoV-2 re-exposure. This patient provides an example of anti-Spike immunity able to control infection to asymptomatic level.Interpretations: The antibodies from SARS-CoV-2 convalescent patients persist over 14 months and continue to maintain cross-reactivity and strong functional properties.Trial Registration: This study included plasma donors who participated in a phase 2 study (NCT04408209 and NCT04743388)Funding: This work was supported by funds from the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research to G.N.P. and B.K.F. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.Declaration of Interest: The authors have declared that no conflict of interest exists.Ethical Approval: The study was approved by the local ethics committees of all participating hospitals.