Safety and Immunogenicity of a Severe Acute Respiratory Syndrome Coronavirus 2 Spike Subunit Vaccine Stabilized in the Prefusion Conformation by a Second-Generation Molecular Clamp and Evaluated in Adults Aged 18–55 Years: A Randomized, Double-Blind, Active Comparator, Phase I Trial - Report - MDSpire
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Safety and Immunogenicity of a Severe Acute Respiratory Syndrome Coronavirus 2 Spike Subunit Vaccine Stabilized in the Prefusion Conformation by a Second-Generation Molecular Clamp and Evaluated in Adults Aged 18–55 Years: A Randomized, Double-Blind, Active Comparator, Phase I Trial
Phase I Trial of MC2-Stabilized SARS-CoV-2 Spike Subunit Vaccine UQSC2 in Adults
Overview
A phase I randomized, double-blind trial compared the safety and immunogenicity of the MC2 molecular clamp–stabilized SARS-CoV-2 spike subunit vaccine UQSC2 with the approved NVX-CoV2373 vaccine in adults aged 18 to 50 years. Both vaccines were well tolerated and elicited comparable neutralizing antibody responses against the Wuhan strain of SARS-CoV-2 over a 6-month period.
Background
The molecular clamp platform stabilizes viral class I fusion proteins in their prefusion conformation, facilitating subunit vaccine production with scalable manufacturing. The original molecular clamp design included HIV-1 gp41 sequences, which interfered with HIV diagnostic tests, halting vaccine development. A second-generation molecular clamp (MC2) was engineered to avoid this issue and demonstrated equivalent stability and immunogenicity in preclinical studies. This trial evaluated the safety and immune response of the MC2-stabilized SARS-CoV-2 spike vaccine, UQSC2, as a booster in adults previously vaccinated with mRNA COVID-19 vaccines.
Data Highlights
Parameter
UQSC2 (n=35)
NVX-CoV2373 (n=35)
Age Range
18–50 years
18–50 years
Previous mRNA doses
≥3 doses
≥3 doses
Safety Profile
Well tolerated
Well tolerated
Neutralizing Antibody Response
Comparable increase vs Wuhan strain
Comparable increase vs Wuhan strain
Follow-up Duration
183 days
183 days
Key Findings
UQSC2 vaccine using the MC2 molecular clamp was as safe and well tolerated as the authorized NVX-CoV2373 vaccine.
Both vaccines elicited comparable neutralizing antibody responses against the prototypic Wuhan SARS-CoV-2 strain.
The MC2 molecular clamp platform avoids HIV-1 sequence interference seen in the original clamp design.
UQSC2 induced robust humoral and cellular immune responses when administered as a booster after prior mRNA vaccination.
The trial supports the MC2 platform's potential for rapid vaccine development against emerging SARS-CoV-2 variants and other respiratory viruses.
Clinical Implications
The MC2 molecular clamp platform enables production of stable, immunogenic subunit vaccines without HIV diagnostic interference, making it a promising tool for future vaccine development. UQSC2 demonstrated safety and immunogenicity comparable to an approved subunit vaccine, supporting its potential use as a booster in previously mRNA-vaccinated adults. This platform could facilitate rapid response to novel viral threats with scalable manufacturing.
Conclusion
The phase I trial demonstrated that the MC2-stabilized SARS-CoV-2 spike subunit vaccine UQSC2 is safe and elicits immune responses comparable to an authorized comparator vaccine. These results validate the MC2 platform as a versatile approach for developing vaccines against SARS-CoV-2 variants and other respiratory pathogens.
by Keith J Chappell, Francesca L Mordant, Alberto A Amarilla, Naphak Modhiran, Benjamin Liang, Zheyi Li, Julia A Lackenby, Noushin Jaberolansar, Jake O’Donnell, Vivian Kienzle, Varsha Kommajosyula, Nicolas Tardiota, Jillian K Bennet, Christina L Henderson, Rhiannon L Dalrymple, Justin Goh, Kym Hoger, Marianne Gillard, Martina L Jones, Karen Hughes, Ben Hughes, James Barnes, Patrick C Reading, Charani Ranasinghe, Kanta Subbarao, Trent P Munro, Paul R Young, Daniel Watterson
