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

Abstract

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 (NHP). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multi-functional 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 (IC50) titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHP were challenged intranasally and intratracheally with a high dose (3x106 plaque forming units, PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike protein-specific IgG antibody responses in the lung as early as two days post 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 NHP and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection.

mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron

“…Avidity was measured as described previously (Francica et al, 2021) in an adapted ELISA assay. Briefly, ELISA against S-2P was performed in the absence or presence of sodium thiocyanate (NaSCN) and developed with HRP-conjugated goat anti-monkey IgG (H+L) secondary antibody (Invitrogen) and SureBlue 3,3′,5,5′-tetramethylbenzidine (TMB) microwell peroxidase substrate (1-Component; SeraCare) and quenched with 1 N H 2 SO 4 .…”

A Perspective on the Roles of Adjuvants in Developing Highly Potent COVID-19 Vaccines

“…Researchers have combined the soluble prefusion-stabilized S trimers (preS dTM) from SARS-CoV-2 with the adjuvant AS03 and injected it twice into NHPs. Results suggest that the IgG antibodies induced by this adjuvanted vaccine can protect NHPs against SARS-CoV-2 infection [33]. Similarly, interim results from a randomized, placebo-controlled phase 1-2 dose-range study in healthy adults demonstrated that the preS dTM vaccine adjuvanted with AS03 has effectively promoted the production of anti-virus neutralizing antibodies [34].…”

Breadth of SARS-CoV-2 Neutralization and Protection Induced by a Nanoparticle Vaccine

“…Our studies with NTD-scNP immunization demonstrated neutralizing antibodies may not be the only mediators of protection. While the RBD subunit has been shown to protect against SARS-CoV-2 challenge in animal models (Dai et al, 2020; Francica et al, 2021; Pino et al, 2021; Saunders et al ., 2021; Yang et al, 2020), the NTD is also an immunodominant region for neutralizing antibodies (Cerutti et al, 2021; Chi et al, 2020; Li et al ., 2021a; Martinez et al, 2021b; McCallum et al, 2021; Voysey et al, 2021). However, NTD is the site of multiple mutations and NTD antibody neutralization is, in general, less potent than RBD antibodies.…”