tetano
Editor, Senior Moderator
Vaccine
. 2022 Jan 31;S0264-410X(22)00077-9.
doi: 10.1016/j.vaccine.2022.01.043. Online ahead of print.
Phase I interim results of a phase I/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS-452
Yester F Janssen[SUP] 1 [/SUP], Eline A Feitsma[SUP] 1 [/SUP], Hendrikus H Boersma[SUP] 2 [/SUP], David G Alleva[SUP] 3 [/SUP], Thomas M Lancaster[SUP] 3 [/SUP], Thillainaygam Sathiyaseelan[SUP] 3 [/SUP], Sylaja Murikipudi[SUP] 3 [/SUP], Andrea R Delpero[SUP] 3 [/SUP], Melanie M Scully[SUP] 3 [/SUP], Ramya Ragupathy[SUP] 3 [/SUP], Sravya Kotha[SUP] 3 [/SUP], Jeffrey R Haworth[SUP] 3 [/SUP], Nishit J Shah[SUP] 3 [/SUP], Vidhya Rao[SUP] 3 [/SUP], Shashikant Nagre[SUP] 3 [/SUP], Shannon E Ronca[SUP] 4 [/SUP], Freedom M Green[SUP] 4 [/SUP], Ari Aminetzah[SUP] 5 [/SUP], Frans Sollie[SUP] 6 [/SUP], Schelto Kruijff[SUP] 7 [/SUP], Maarten Brom[SUP] 5 [/SUP], Gooitzen M van Dam[SUP] 5 [/SUP], Todd C Zion[SUP] 8 [/SUP]
Affiliations
Abstract
To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18-65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.
Keywords: AKS-452; COVID-19; Coronavirus; Fc-fusion; Infectious disease; Pandemic; Prophylaxis; SARS-CoV-2; Vaccine.
. 2022 Jan 31;S0264-410X(22)00077-9.
doi: 10.1016/j.vaccine.2022.01.043. Online ahead of print.
Phase I interim results of a phase I/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS-452
Yester F Janssen[SUP] 1 [/SUP], Eline A Feitsma[SUP] 1 [/SUP], Hendrikus H Boersma[SUP] 2 [/SUP], David G Alleva[SUP] 3 [/SUP], Thomas M Lancaster[SUP] 3 [/SUP], Thillainaygam Sathiyaseelan[SUP] 3 [/SUP], Sylaja Murikipudi[SUP] 3 [/SUP], Andrea R Delpero[SUP] 3 [/SUP], Melanie M Scully[SUP] 3 [/SUP], Ramya Ragupathy[SUP] 3 [/SUP], Sravya Kotha[SUP] 3 [/SUP], Jeffrey R Haworth[SUP] 3 [/SUP], Nishit J Shah[SUP] 3 [/SUP], Vidhya Rao[SUP] 3 [/SUP], Shashikant Nagre[SUP] 3 [/SUP], Shannon E Ronca[SUP] 4 [/SUP], Freedom M Green[SUP] 4 [/SUP], Ari Aminetzah[SUP] 5 [/SUP], Frans Sollie[SUP] 6 [/SUP], Schelto Kruijff[SUP] 7 [/SUP], Maarten Brom[SUP] 5 [/SUP], Gooitzen M van Dam[SUP] 5 [/SUP], Todd C Zion[SUP] 8 [/SUP]
Affiliations
- PMID: 35115195
- PMCID: PMC8802018
- DOI: 10.1016/j.vaccine.2022.01.043
Abstract
To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18-65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain.
Keywords: AKS-452; COVID-19; Coronavirus; Fc-fusion; Infectious disease; Pandemic; Prophylaxis; SARS-CoV-2; Vaccine.