A First-in-Human Trial to Evaluate the Safety and Immunogenicity of a G Protein-Based Recombinant Respiratory Syncytial Virus Vaccine in Healthy Adults 18–45 Years of Age

Abstract

Background: With the enormous morbidity and mortality caused by respiratory syncytial virus (RSV) infections among infants and the elderly, vaccines against RSV infections are in large market demand. Methods: We conducted a first-in-human (FIH), randomized, double-blind, placebo-controlled dose escalation study to evaluate the safety and immunogenicity response of the rRSV vaccine (BARS13) in healthy adults aged 18–45. A total of 60 eligible participants were randomly assigned to receive one of four dose levels or vaccination regimens of BARS13 or placebo at a 4:1 ratio. Results: The mean age was 27.40, and 23.3% (14/60) were men. No treatment-emergent adverse events (TEAEs) led to study withdrawal within 30 days after each vaccination. No serious adverse event (SAE) was reported. Most of the treatment-emergent adverse events (TEAEs) recorded were classified as mild. The high-dose repeat group had a serum-specific antibody GMC of 885.74 IU/mL (95% CI: 406.25–1931.17) 30 days after the first dose and 1482.12 IU/mL (706.56–3108.99) 30 days after the second dose, both higher than the GMC in the low-dose repeat group (885.74 IU/mL [406.25–1931.17] and 1187.10 IU/ mL [610.01–2310.13]). Conclusions: BARS13 had a generally good safety and tolerability profile, and no significant difference in terms of adverse reaction severity or frequency was observed between different dose groups. The immune response in repeat-dose recipients shows more potential in further study and has guiding significance for the dose selection of subsequent studies.

Design and Preclinical Evaluation of a Nanoparticle Vaccine against Respiratory Syncytial Virus Based on the Attachment Protein G

“…Several vaccine approaches based on RSV G have been investigated, utilizing the CCD as a stand-alone antigen or as an add-on component, co-formulated with an RSV F vaccine [ 21 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Multiple strategies have been explored to overcome the limited immunogenicity of the CCD peptide, including multimerization of short peptides and display on synthetic, as well as self-assembling nanoparticles.…”

Vaccination for Respiratory Syncytial Virus: A Narrative Review and Primer for Clinicians

“…Multiple vaccine platforms are being developed for RSV vaccination and for various target groups [ 87 ]. Virus-like particle-based vaccines [ 69 ], mRNA-based vaccines [ 70 , 71 ], G protein-based recombinant vaccines [ 72 ], Mycobacterium bovis BCG-based recombinant vaccines [ 73 ], adenovirus vector-based vaccines [ 74 , 75 , 76 ] (development has been halted by its manufacturer in March 2023 after portfolio review), and Modified Vaccinia Ankara (MVA) poxvirus-based recombinant vaccines [ 78 ] have been immunogenic and well-tolerated in early trials in healthy participants. Beyond the trials in healthy participants, although a large multinational trial of RSV fusion protein nanoparticle vaccine did not reach its desired efficacy outcome [ 80 ], other platforms involving adenovirus vector-based vaccines [ 81 , 82 , 84 ] and mRNA-based vaccines appear more promising.…”

Respiratory Syncytial Virus Vaccines: Analysis of Pre-Marketing Clinical Trials for Immunogenicity in the Population over 50 Years of Age

“…BARS13, manufactured by Advaccine Biopharmaceuticals Co., uses the RSV-G protein as the antigen, co-administered with cyclosporine A as the adjuvant [59,60]. Evaluation of the vaccine in younger adults aged 18-45 years in a Phase I clinical trial (NCT04851977) revealed a dose-dependent induction of immunity regarding specific antibodies against the RSV-G protein [59]. Subsequently, a Phase II study (NCT04681833) followed to assess the vaccine in older adults aged 60-80 years.…”