biostudies-literatureUnknown13(607)Francica JRBiomedical Advanced Research and Development AuthoritySanofi PasteurGlaxoSmithKline foundationNational Institutes of HealthAdjuvanted 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.Science translational medicineeabi4547https://www.ebi.ac.uk/biostudies/studies/S-EPMC9266840biostudies-literatureProtective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates.PMC9266840Shin STylor AAndersen HZhu ALPessaint LRuiz SMoore INTodd JMWerner APHaynes BFEdara VVAndrew SFKwong PDGorman MJTeng ITVan De Wetering RLi DLecouturier VO'Connell SKoutsoukos MSullivan NJCasimiro DFrancica JRBerry CLewis MGFloyd KCook ASeder RAFlebbe DRLamb ETibbitts TMcCarthy EJohnston TSNurmukhambetova STFischinger SCorbett KSChicz RRoederer MDouek DCVan Ry ATucker CFlach BNoe ATAlter GSuthar MSDonaldson MMFoulds KEFu TMFlynn BJBoyoglu-Barnum Svan der Most RZhou TDodson AAtyeo CGraham BSGagne MDavis RLMcDermott AGutzeit CLai LfalseProtective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge 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.2021-01-01T00:00:00Z2021 Aug2024-11-08T18:01:02.796Z2024-11-08T18:01:02.796ZS-EPMC92668403431582510.1126/scitranslmed.abi4547