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

Cheng, Xiuzhen; Zhao, Gan; Dong, Anjie; He, Zhonghuai; Wang, Jiarong; Jiang, Baoen; Wang, Bo; Wang, Miaomiao; Huai, Xuefen; Zhang, Shijie; Feng, Suhua; Qin, Hong; Wang, Bin

doi:10.1101/2022.12.27.22283128

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…We are at an exciting time in RSV vaccine development for older adults, with expanding technologies and several candidates currently in early-stage clinical trials in addition to those discussed in late-stage clinical trials [ 87 ]. Three RSV G-protein-based vaccines are in clinical development, including Advaccine’s BARS13/ADV110, which contains recombinant RSV G protein and cyclosporine A, and has entered Phase 2 clinical testing in older adults aged 60–80 years after demonstrating immunogenicity and safety in Phase 1 [ 87 , 88 , 89 ]. Meanwhile, a candidate targeting the SH protein of RSV A demonstrated high immunogenicity with sustained antigen-specific antibody responses alongside an acceptable safety profile in Phase 1 testing of adults aged 50–64 years [ 90 ].…”

Section: Other Vaccines In Early Developmentmentioning

confidence: 99%

The Quest for a Respiratory Syncytial Virus Vaccine for Older Adults: Thinking beyond the F Protein

Jenkins¹,

Hoet²,

Hochrein

et al. 2023

Vaccines

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Respiratory syncytial virus (RSV) is a common cause of paediatric respiratory tract infection and causes a significant health burden in older adults. Natural immunity to RSV is incomplete, permitting recurrent symptomatic infection over an individual’s lifespan. When combined with immunosenescence, this increases older adults’ susceptibility to more severe disease symptoms. As RSV prophylaxis is currently limited to infants, older adults represent an important target population for RSV vaccine development. The relationship between RSV and our immune systems is complex, and these interactions require deeper understanding to tailor an effective vaccine candidate towards older adults. To date, vaccine candidates targeting RSV antigens, including pre-F, F, G (A), G (B), M2-1, and N, have shown efficacy against RSV infection in older adults in clinical trial settings. Although vaccine candidates have demonstrated robust neutralising IgG and cellular responses, it is important that research continues to investigate the RSV immune response in order to further understand how the choice of antigenic target site may impact vaccine effectiveness. In this article, we discuss the Phase 3 vaccine candidates being tested in older adults and review the hurdles that must be overcome to achieve effective protection against RSV.

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Section: Other Vaccines In Early Developmentmentioning

confidence: 99%

The Quest for a Respiratory Syncytial Virus Vaccine for Older Adults: Thinking beyond the F Protein

Jenkins¹,

Hoet²,

Hochrein

et al. 2023

Vaccines

View full text Add to dashboard Cite

show abstract

“…Currently, there are only two RSV vaccines approved by the US Food and Drug Administration and studies in SOT are underway, summarized in Table 6 along with investigational vaccines and other passive immunization agents against RSV currently undergoing development [80,83–94].…”

Section: Prevention Of Rsvmentioning

confidence: 99%

“…Recent trials show benefit against medically attended RSV-associated LRI in at-risk preterm and healthy late preterm and term infants [81,82]. Currently, there are only two RSV vaccines approved by the US Food and Drug Administration and studies in SOT are underway, summarized in Table 6 along with investigational vaccines and other passive immunization agents against RSV currently undergoing development [80,[83][84][85][86][87][88][89][90][91][92][93][94].…”

Section: Prevention Of Rsvmentioning

confidence: 99%

Respiratory viral infections including COVID-19 in solid organ transplantation

Lo,

Kumar

2023

Current Opinion in Organ Transplantation

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Purpose of review Respiratory viral infections are prevalent and contribute to significant morbidity and mortality among solid organ transplant (SOT) recipients. We review updates from literature on respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the SOT recipient. Recent findings With the wider availability and use of molecular diagnostic tests, our understanding of the epidemiology and impact of respiratory viruses in the SOT population continues to expand. While considerable attention has been given to the coronavirus disease 2019 (COVID-19) pandemic, the advances in prevention and treatment strategies of SARS-CoV-2 offered valuable insights into the development of new therapeutic options for managing other respiratory viruses in both the general and SOT population. Summary Respiratory viruses can present with a diverse range of symptoms in SOT recipients, with potentially associated acute rejection and chronic lung allograft dysfunction in lung transplant recipients. The epidemiology, clinical presentations, diagnostic approaches, and treatment and preventive strategies for clinically significant RNA and DNA respiratory viruses in SOT recipients are reviewed. This review also covers novel antivirals, immunologic therapies, and vaccines in development for various community-acquired respiratory viruses.

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“…The results showed no serious adverse events in 18 to 45-year-old volunteers. The vaccine induced a strong humoral immune response, with increased levels of RSV-specific antibodies [19]. The recombinant G protein is a promising candidate for -5 -developing a subunit RSV vaccine, and further testing is needed in the elderly population.…”

Section: Introductionmentioning

confidence: 99%

A Phase 2 random, double-blind, placebo-controlled study of the safety and immunogenicity of a recombinant G protein-based respiratory syncytial virus vaccine in healthy older adults

Zhang,

Zhao,

Cheng

et al. 2023

Preprint

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Background: Respiratory syncytial virus (RSV) is an important cause of disease in older adults. Vaccines against RSV infections and respiratory diseases are in large market demand. Although there are currently two licensed RSV-based pre-F antigen vaccines available for older adults, no G antigen-based RSV vaccine is authorized. This phase 2 study aimed to evaluate the safety and immunogenicity of a recombinant G protein-based RSV vaccine in this population. Methods: A phase-2 randomized, double-blind, placebo-controlled, dose-ranging study was conducted to evaluate the safety, tolerability and immunogenicity of the BARS13 (rRSV G protein with CsA) when administered by an intramuscular (IM) injection to healthy participants 60 to 80 years old. A total of 125 eligible participants were randomized in a 3:1 ratio (vaccine versus placebo) for Cohorts 1 and 2 and randomized in a 2:1 ratio for Cohort 3 to receive one of the three treatment regimens or placebo. Results: The average age was 65.3, and 50.4% (63/125) were men. Until the interim analysis (4 weeks following the last vaccination), no treatment-related SAE occurred. TEAEs did not increase with vaccination dosage or frequency. All adverse effects were mild or moderate, not severe or life-threatening. BARS13 vaccination increased IgG anti-RSV antibody levels in all cohorts, but higher doses and frequency boosted immune responses significantly. The high-dose thrice-administered recipients had serum-specific IgG antibody GMC of 881.0 IU/mL (95% CI: 794.5-1473.4) before the first dose (Week 0), 1116.3 IU/mL (95% CI:990.7-1772.5) 4 weeks after the first dose (Week 4), 1309.4IU/mL (95% CI: 1162.8-2041.5) 4 weeks after the second dose (Week 8), and1359.6 IU/mL (95% CI: 1197.9-2525.7) 4 weeks after the third dose (Week 12). For the low-dose twice-administered recipients, 84% responded at 4 weeks after the first immunization (Week 4) and 83.3% at 4 weeks after the second (Week 8). The high-dose twice-administered recipients had 95.5% response at 4 weeks after the first immunization (Week 4) and 72.2% at 4 weeks after the second (Week 8). At Week 4, 85.7% of high-dose thrice-administered recipients responded, 85.2% at Week 8, and 79.2% at Week 12. Conclusions: The study demonstrates the safety and tolerability of BARS13 across different dose groups. Adverse reactions were not significantly different among participants receiving varying doses of BARS13. Levels of anti-G antibodies exhibited a dose- and frequency-dependent responses in the older population. The continuous upward trend in antibody concentration up to the interim analysis is promising for the effectiveness of BARS13. Key words: Respiratory syncytial virus, Vaccine, Safety, Immunogenicity

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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

Cited by 4 publications

References 25 publications

The Quest for a Respiratory Syncytial Virus Vaccine for Older Adults: Thinking beyond the F Protein

The Quest for a Respiratory Syncytial Virus Vaccine for Older Adults: Thinking beyond the F Protein

Respiratory viral infections including COVID-19 in solid organ transplantation

A Phase 2 random, double-blind, placebo-controlled study of the safety and immunogenicity of a recombinant G protein-based respiratory syncytial virus vaccine in healthy older adults

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