Interim Results from a Phase I Trial of Novel SARS-CoV-2 Beta Variant Receptor-Binding Domain Recombinant Protein and mRNA Vaccines as a 4 ^th Dose Booster

Published: Jan. 1, 2023

Background: SARS-CoV-2 booster vaccination should ideally enhance protection against variants and minimise immune imprinting. This Phase I trial evaluated two vaccines targeting beta-variant receptor-binding domain (RBD): a recombinant dimeric RBD-human IgG1 Fc-fusion protein, an mRNA encoding membrane-anchored RBD. Methods: 76 healthy adults aged 18–64y, previously triple vaccinated with licensed vaccines, were randomised to receive 4th dose of either adjuvanted (MF59®, CSL Seqirus) protein vaccine (5, 15 or 45µg, N=32), (10, 20, 50µg, placebo (saline, N=12) at least 90 days after 3rd boost infection. Bleeds occurred on 1 (prior vaccination), 8, 29. ClinicalTrials.gov NCT05272605.Findings: No vaccine-related serious medically attended adverse events occurred. The reactogenicity was mild, whereas the moderately reactogenic higher levels. Best anti-RBD antibody responses resulted from doses each vaccine. A similar pattern seen live virus neutralisation surrogate, pseudovirus assays. Breadth response demonstrated BA.5 more recent omicron subvariants (XBB, XBB.1.5 BQ.1.1). Binding titres for both comparable those bivalent Both enhanced CD4+ CD8+ T cell activation.Interpretation: There no safety concerns profile mild vaccines. showed strong boosting beta, ancestral strains.Trial Registration: study is registered www.clinicaltrials.gov (NCT05272605).Funding: Medical Research Future Fund, philanthropies Jack Ma Foundation IFM investors.Declaration Interest: in this result independent University Melbourne Monash research development, funding provided by Australian Government’s Fund (MRFF), National Health Council (NHMRC) philanthropic funders. MF59 protein-RBD candidate donated Seqirus. One author (SR) employee Seqirus he also has adjunct (honorary) appointment Melbourne. Several authors have received consulting various commercial entities, but none judged be conflict work presented.Ethical Approval: reviewed approved Royal Hospital Human Ethics Committee conducted under Clinical Trial Notification (CTN) Scheme (CTN ID: 04968-1) administered Therapeutic Goods Administration. All participants written informed consent prior enrolment.

Language: Английский

IMMUNOLOGICAL STORM AND MULTIPLE ORGAN DAMAGE BY COVID-19

Medicine in Omics, Journal Year: 2024, Volume and Issue: 11, P. 100034 - 100034

Published: Jan. 25, 2024

The official recording outbreak Covid-19 virus was in Dec 2019. When it affects humans, almost all age groups, especially aged people. COVID-19 becomes a Global pandemic within short period. primary consequence of this infection is that targets the individual's respiratory system and causes severe acute syndrome (SARS-CoV-2). Research efforts were made internationally to find proper vaccine. Here, with mechanism action, review provides mechanism, Immunological changes, associated organ damage.

Language: Английский

mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting

Molecular Therapy — Methods & Clinical Development, Journal Year: 2024, Volume and Issue: 32(4), P. 101380 - 101380

Published: Nov. 15, 2024

Language: Английский