Highly immunogenic influenza virus-like particles containing B-cell-activating factor (BAFF) for multi-subtype vaccine development

In the midst of the ongoing COVID-19 coronavirus pandemic, influenza virus remains a major threat to public health due to its potential to cause epidemics and pandemics with significant human mortality. Cases of H7N9 human infections emerged in eastern China in 2013 and immediately raised pandemic concerns as historically, pandemics were caused by the introduction of new subtypes into immunologically naïve human populations. Highly pathogenic H7N9 cases with severe disease were reported recently, indicating the continuing public health threat and the need for a prophylactic vaccine. Here we review the development of recombinant influenza virus-like particles (VLPs) as vaccines against H7N9 virus. Several approaches to vaccine development are reviewed including the expression of VLPs in mammalian, plant and insect cell expression systems. Although considerable progress has been achieved, including demonstration of safety and immunogenicity of H7N9 VLPs in the human clinical trials, the remaining challenges need to be addressed. These challenges include improvements to the manufacturing processes, as well as enhancements to immunogenicity in order to elicit protective immunity to multiple variants and subtypes of influenza virus.

Download Full-text

Production of Multi-Subtype Influenza Virus-Like Particles by Molecular Fusion with BAFF or APRIL for Vaccine Development

Methods in Molecular Biology - The TNF Superfamily ◽

10.1007/978-1-0716-1130-2_10 ◽

2020 ◽

pp. 139-153

Author(s):

Ting-Hsuan Chen ◽

Jo-Yu Hong ◽

Chia-Chyi Liu ◽

Chung-Chu Chen ◽

Jia-Tsrong Jan ◽

...

Keyword(s):

Influenza Virus ◽

Vaccine Development ◽

Virus Like Particles

Download Full-text

Faculty Opinions recommendation of Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1160897.627349 ◽

2009 ◽

Author(s):

Sarah Gaffen ◽

Allen Ho

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cell ◽

Lupus Erythematosus ◽

Cell Biology ◽

Interleukin 17 ◽

Systemic Lupus ◽

B Cell Activating Factor

Download Full-text

Faculty Opinions recommendation of Formation of virus-like clusters is an intrinsic property of the tumor necrosis factor family member BAFF (B cell activating factor).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.719555197.793546484 ◽

2018 ◽

Author(s):

David Hayes

Keyword(s):

Tumor Necrosis Factor ◽

B Cell ◽

Family Member ◽

Tumor Necrosis ◽

Intrinsic Property ◽

Tumor Necrosis Factor Family ◽

B Cell Activating Factor ◽

Necrosis Factor

Download Full-text

B-cell activating factor BAFF as a novel alert marker for the immunological risk stratification after kidney transplantation

Immunologic Research ◽

10.1007/s12026-021-09205-4 ◽

2021 ◽

Author(s):

Antonia Margarete Schuster ◽

N. Miesgang ◽

L. Steines ◽

C. Bach ◽

B. Banas ◽

...

Keyword(s):

Kidney Transplantation ◽

B Cell ◽

Graft Function ◽

Risk Profile ◽

Kidney Transplant Recipients ◽

Post Transplantation ◽

Antibody Mediated Rejection ◽

B Cell Activating Factor ◽

Medium Risk ◽

Patients At Risk

AbstractThe B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient’s individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required.

Download Full-text

Hepatitis B core-based virus-like particles: A platform for vaccine development in plants

Biotechnology Reports ◽

10.1016/j.btre.2021.e00605 ◽

2021 ◽

Vol 29 ◽

pp. e00605

Author(s):

Maryam Moradi Vahdat ◽

Farshad Hemmati ◽

Abozar Ghorbani ◽

Daria Rutkowska ◽

Alireza Afsharifar ◽

...

Keyword(s):

Hepatitis B ◽

Vaccine Development ◽

Virus Like Particles

Download Full-text

Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

Nature Communications ◽

10.1038/s41467-021-21444-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Adam K. Wheatley ◽

Jennifer A. Juno ◽

Jing J. Wang ◽

Kevin J. Selva ◽

Arnold Reynaldi ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Natural Infection ◽

Population Level ◽

Cell Dynamics ◽

Follicular Helper ◽

Cell Immunity ◽

Specific Igg ◽

Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

Download Full-text