Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates.

Rapid response: Protein subunit–based vaccines have been used extensively for protection against viral infections. Here, Francica et al. tested a protein subunit vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The authors vaccinated nonhuman primates with soluble prefusion-stabilized spike trimers (preS dTM) plus the adjuvant AS03, an oil-in-water emulsion. The authors found that preS dTM plus AS03 induced robust antibody and cellular immune responses that protected nonhuman primates from disease when challenged with SARS-CoV-2. This rapid protection, with increases in antibodies specific to spike protein observable as soon as 2 days after infection, provides evidence of a critical anamnestic antibody response. Antibodies elicited by preS dTM vaccination are protective against SARS-CoV-2 in nonhuman primates. Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHPs were challenged intranasally and intratracheally with a high dose (3 × 10⁶ plaque forming units) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days after challenge, vaccinated NHPs showed rapid control of viral replication in both the upper and lower airways. Vaccinated NHPs also had increased spike protein–specific immunoglobulin G (IgG) antibody responses in the lung as early as 2 days after challenge. Moreover, passive transfer of vaccine-induced IgG to hamsters mediated protection from subsequent SARS-CoV-2 challenge. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine were sufficient to mediate protection against SARS-CoV-2 in NHPs and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection. [ABSTRACT FROM AUTHOR]