Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster

Nolan, Terry M.; Deliyannis, Georgia; Griffith, Maryanne; Braat, Sabine; Allen, Lilith F.; Audsley, Jennifer; Chung, Amy W.; Ciula, Marcin; Gherardin, Nicholas A.; Giles, Michelle L.; Gordon, Tom P.; Grimley, Samantha L.; Horng, Lana; Jackson, David C.; Juno, Jennifer A.; Kedzierska, Katherine; Kent, Stephen J.; Lewin, Sharon R.; Littlejohn, Mason; McQuilten, Hayley A.; Mordant, Francesca L.; Nguyen, Thi H.O.; Soo, Vanessa Pac; Price, Briony; Purcell, Damian F.J.; Ramanathan, Pradhipa; Redmond, Samuel J.; Rockman, Steven; Ruan, Zheng; Sasadeusz, Joseph; Simpson, Julie A.; Subbarao, Kanta; Fabb, Stewart A.; Payne, Thomas J.; Takanashi, Asuka; Tan, Chee Wah; Torresi, Joseph; Wang, Jing Jing; Wang, Lin-Fa; Al-Wassiti, Hareth; Wong, Chinn Yi; Zaloumis, Sophie; Pouton, Colin W.; Godfrey, Dale I.

doi:10.1016/j.ebiom.2023.104878

Cited by 8 publications

(6 citation statements)

References 39 publications

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“…19 Unlike this trial, the population included in other trials assessing boosting with recombinant protein vaccines were highly homogenous regarding the primary vaccination scheme, mostly based on mRNA (BNT162b2 or mRNA-1273), Ad26, and ChAdOx-1 vaccines. [18][19][20][21] However, at least seven vaccines based on different platforms were applied as primary and booster doses in Argentina when we initiated this study. 22 This trial showed robust nAb responses regardless of the previous vaccination scheme (six platforms) and the number of previous booster doses (no booster, one, or two).…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Safety of Gamma, Omicron BA.4/5 and Bivalent SARS-CoV-2 RBD-based Protein Booster Vaccines in Adults Previously Immunized with Different Vaccine Platforms: a Phase II/III, Randomized, Clinical Trial

Perez-Marc,

Coria,

Ceballos

et al. 2024

Preprint

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Background: This study (ARVAC-F2-3-002) assessed the immunogenicity, safety, and tolerability of a recombinant booster vaccine (ARVAC) containing the receptor binding domain of the SARS-CoV-2 Spike protein in three different versions: Gamma (ARVACGamma), Omicron BA.4/5 (ARVACOmicron), and Gamma/Omicron Bivalent (ARVACBivalent). Methods: Randomized, double-blind, crossover, placebo-controlled, multicenter (11 centers in Argentina) Phase II/III trial including adult volunteers previously vaccinated against SARS-CoV-2 with ≤3 booster doses. Participants were randomized to receive ARVACGamma (50 μg)+placebo and vice-versa (1:1 ratio) (Phase II), and ARVACGamma (50 μg)+placebo, ARVACOmicron (50 μg)+placebo, and ARVACBivalent (Gamma/Omicron 25 μg/25 μg)+placebo and vice-versa (Phase III) (1:1:1:1:1:1 ratio) 28 days apart. The primary endpoint was the seroconversion rate of neutralizing antibodies compared to placebo. The vaccine immunogenicity was considered acceptable at >75% seroconversion rate to variants homologous to the antigen contained in the vaccine (prespecified primary endpoint). Results: Participants (n=2012) (mean 48.2 years, SD 16.7; 48.1% women) were randomized and allocated to ARVACGamma (n=232 in Phase II and n=592 in Phase III), ARVACOmicron (n=594), and ARVACBivalent (n=594); 232 in Phase II and 370 in each Phase III group were included in the immunogenicity subset. Seroconversion rates to all SARS-CoV-2 variants were significantly higher after receiving any vaccine than placebo. All vaccine versions met the prespecified primary endpoint in all participants and in those 18−60 years old. In participants >60 years, the ARVACOmicron and the ARVACBivalent met the prespecified primary endpoint, whereas the ARVACGamma did not. The ARVACBivalent induced seroconversion rates were significantly higher than 75% across all tested SARS-CoV-2 variants (homologous and heterologous) and age groups. No vaccine-related serious adverse events were recorded; most local and systemic adverse events were grade 1-2. Conclusion: Booster vaccination with Gamma, Omicron BA.4/5, and Bivalent protein subunit recombinant ARVAC vaccine versions elicited protective neutralizing antibody responses to several SARS-CoV-2 variants, with very low reactogenicity and a favorable safety profile. Trial registration:NCT05752201

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Section: Discussionmentioning

confidence: 99%

Immunogenicity and Safety of Gamma, Omicron BA.4/5 and Bivalent SARS-CoV-2 RBD-based Protein Booster Vaccines in Adults Previously Immunized with Different Vaccine Platforms: a Phase II/III, Randomized, Clinical Trial

Perez-Marc,

Coria,

Ceballos

et al. 2024

Preprint

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“…For LNP formulation and cell culture experiments, mRNA used for general formulation studies was uncapped native SARS-CoV2 RBD-TM mRNA (i.e., a less active form of an mRNA vaccine designed locally 38 ). mRNA used for biological activity studies was capped (using TriLink CleanCap Cap 1 reagent), and the chemically modified Nanoluciferase mRNA was prepared using N1-methyl-pseudoUTP in place of UTP.…”

Section: Methodsmentioning

confidence: 99%

“…Reduction of cell viability by more than 30% is considered as an in vitro cytotoxic effect. 38 showed significant cytotoxicity at concentrations above 0.3125 mg mL −1 (Figure S15). To the best of our knowledge, the difference in cytotoxicity between mono-and diacyl polymer− lipid conjugates has not been reported.…”

Section: Fabrication and Biophysical Characterization Of Lnpsmentioning

confidence: 99%

Tailored Monoacyl Poly(2-oxazoline)- and Poly(2-oxazine)-Lipids as PEG-Lipid Alternatives for Stabilization and Delivery of mRNA-Lipid Nanoparticles

He,

Payne,

Takanashi

et al. 2024

Biomacromolecules

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“…We showed that in animal models, booster vaccines based on the Beta variant could broaden immunity against divergent VOCs. 12 Researchers at The University of Melbourne and Monash Institute of Pharmacological Sciences (MIPS) developed two Beta-based vaccine candidates (protein and mRNA respectively) that showed promise in Phase I clinical testing 13 (Table 1). In individuals who had already received three COVID-19 vaccine doses, both candidates were able to boost antibody responses, including against the highly immune-evasive Omicron subvariants XBB.1.5 and BQ.1.1.…”

Section: Improved Variant-based Vaccinesmentioning

confidence: 99%

“…In individuals who had already received three COVID-19 vaccine doses, both candidates were able to boost antibody responses, including against the highly immune-evasive Omicron subvariants XBB.1.5 and BQ.1.1. 13 Vaccines targeted to circulating variants have been the basis for all authorised COVID-19 booster shots. However, the virus has demonstrated the ability to surpass the pace of vaccine development and distribution, as illustrated in Fig.…”

Section: Improved Variant-based Vaccinesmentioning

confidence: 99%

Australia’s COVID-19 vaccine journey: progress and future perspectives

Triccas,

Steain

2024

Microbiol. Aust.

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COVID-19 vaccines have played a pivotal role in reducing SARS-CoV-2 disease severity and mortality. However, evolutionary pressure has resulted in viral variants with increased fitness, greater capacity for immune evasion and higher infectivity. This evolution is exemplified by the emergence of the Omicron subvariants, all of which demonstrate significant escape from vaccine-or infection-induced immunity. Broadly protective vaccines are urgently needed to fight current, emerging and future SARS-CoV-2 variants. Australia is actively contributing to these efforts through the development of innovative vaccination approaches and vaccine delivery platforms.

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Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster

Cited by 8 publications

References 39 publications

Immunogenicity and Safety of Gamma, Omicron BA.4/5 and Bivalent SARS-CoV-2 RBD-based Protein Booster Vaccines in Adults Previously Immunized with Different Vaccine Platforms: a Phase II/III, Randomized, Clinical Trial

Immunogenicity and Safety of Gamma, Omicron BA.4/5 and Bivalent SARS-CoV-2 RBD-based Protein Booster Vaccines in Adults Previously Immunized with Different Vaccine Platforms: a Phase II/III, Randomized, Clinical Trial

Tailored Monoacyl Poly(2-oxazoline)- and Poly(2-oxazine)-Lipids as PEG-Lipid Alternatives for Stabilization and Delivery of mRNA-Lipid Nanoparticles

Australia’s COVID-19 vaccine journey: progress and future perspectives

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