scholarly journals Rabies virus glycoprotein produced in Nicotiana benthamiana is an immunogenic antigen in mice

2021 ◽  
Vol 57 (No. 1) ◽  
pp. 26-35
Author(s):  
Youngmin Park ◽  
Hyangju Kang ◽  
Kyungmin Min ◽  
Nam Hyung Kim ◽  
Minhee Park ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Nicotiana Benthamiana ◽  
Subunit Vaccine ◽  
Transient Transfection ◽  
Effective Vaccine ◽  
Neutralising Antibodies ◽  
Subunit Vaccines ◽  
The Third ◽  
C Terminus ◽  
A Subunit

Rabies remains an infectious disease among humans and animals, and requires the development of an effective vaccine essential to prevent rabies. Advances in molecular biology and biotechnology have led to the development and improvement of many rabies vaccines. Before the third-generation of the vaccine, rabies vaccines were based on the virus itself. Thus, even if effective, these vaccines may not be completely safe, resulting in a strong demand for the development of effective subunit vaccines that do not raise concerns about virus replication and infection in the host. This study investigated the ability of the glycoprotein of the rabies virus to be expressed in tobacco plants (Nicotiana benthamiana) and to induce an immune response in mice. Using a transient transfection, a soluble glycoprotein was successfully expressed in N. benthamiana. Fusing of five histidine residues at the C-terminus enabled the glycoprotein to be easily purified by affinity chromatography. The glycoprotein expressed in the plants was found to be N-glycosylated post-translationally, and the mice immunised with this glycoprotein generated neutralising antibodies against the rabies virus. These results suggest that a glycoprotein produced in the endoplasmic reticulum of N. benthamiana is bioactive, and might be used to generate a subunit vaccine against the rabies virus.

scholarly journals Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19

2021 ◽  
Author(s):  
Jiahao Ma ◽  
Danmei Su ◽  
Yinyan Sun ◽  
Xueqin Huang ◽  
Ying Liang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Receptor Binding ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Phase 1 ◽  
Full Length ◽  
Effective Vaccine ◽  
S Protein ◽  
Closed Conformation ◽  
A Subunit

Within a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 100 million people worldwide with a death toll over 2 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The tightly closed conformation is stabilized by fatty acid and polysorbate 80 binding at the receptor binding domains (RBDs) and the N terminal domains (NTDs) respectively. Additionally, we identified an important pH switch in the WT S-Trimer that shows dramatic conformational change and accounts for its increased stability at lower pH. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine. IMPORTANCE Effective vaccine against SARS-CoV-2 is critical to end the COVID-19 pandemic. Here, using Trimer-Tag technology, we are able to produce stable and large quantities of WT S-Trimer, a subunit vaccine candidate for COVID-19 with high safety and efficacy from animal and Phase 1 clinical trial studies. Cryo-EM structures of the S-Trimer subunit vaccine candidate show that it predominately adopts tightly closed pre-fusion state, and resembles that of the native and full-length spike in detergent, confirming its structural integrity. WT S-Trimer is currently being evaluated in global Phase 2/3 clinical trial. Combining with published structures of the S protein, we also propose a model to dissect the conformation change of the spike protein before receptor binding.

scholarly journals A novel Mycobacterium tuberculosis-specific subunit vaccine provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin

2021 ◽  
Author(s):  
Joshua S Woodworth ◽  
Helena Strand Clemmensen ◽  
Hannah Battey ◽  
Karin Dijkman ◽  
Thomas Lindenstrøm ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Subunit Vaccine ◽  
Cross Reactivity ◽  
Bacillus Calmette Guerin ◽  
Cell Repertoire ◽  
Subunit Vaccines ◽  
Health Crisis ◽  
A Subunit

Tuberculosis (TB) remains a global health crisis. Following encouraging clinical results of subunit vaccination and revaccination with Bacillus Calmette-Guérin (BCG), it has been suggested to combine BCG and subunit vaccines for increased efficacy. Current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study was to design a subunit vaccine that does not share antigens with BCG and explore the advantages of a BCG+subunit vaccine co-administration strategy, where the two vaccines do not cross-react. Eight protective antigens were selected to create a Mycobacterium tuberculosis (Mtb)-specific subunit vaccine, named H107. Whereas subunit vaccines with BCG-shared antigens displayed cross-reactivity to BCG in vivo in both mice and humans, H107 showed no cross-reactivity and did not inhibit BCG colonization in mice. Encouragingly, co-administering H107 with BCG (BCG+H107) led to increased adaptive immune responses against both H107 and BCG leading to improved BCG-mediated immunity. In contrast to subunit vaccines with BCG-shared antigens, 'boosting' BCG with H107 led to substantial expansion of clonal diversity in the T cell repertoire, and BCG+H107 co-administration conferred significantly increased Th17 responses and less differentiated CD4 T cells. CD4 T cells induced by BCG+H107 maintained functional superiority after Mtb infection, and BCG+H107 provided significantly increased long-term protection compared to both BCG and H107 alone, as well as, BCG co-administered with a subunit vaccine composed of antigens shared with BCG. Overall, we identify several advantages of combining an Mtb-specific subunit vaccine with BCG and introduce H107 as a BCG-complementing vaccine with distinctive value for co-administration with BCG.

scholarly journals Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hyon-Xhi Tan ◽  
Jennifer A. Juno ◽  
Wen Shi Lee ◽  
Isaac Barber-Axthelm ◽  
Hannah G. Kelly ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Subunit Vaccine ◽  
Cell Activity ◽  
Receptor Binding Domain ◽  
Protein Subunit ◽  
Neutralising Antibodies ◽  
Subunit Vaccines ◽  
Vaccine Candidates ◽  
Follicular Helper ◽  
T Follicular Helper Cell

AbstractSARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.

scholarly journals Hydrogel-based slow release of a receptor-binding domain subunit vaccine elicits neutralizing antibody responses against SARS-CoV-2

2021 ◽  
Author(s):  
Emily C. Gale ◽  
Abigail E. Powell ◽  
Gillie A. Roth ◽  
Ben S. Ou ◽  
Emily L. Meany ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Subunit Vaccine ◽  
Cytotoxic T Lymphocyte ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Effective Vaccine ◽  
Bolus Administration ◽  
Receptor Binding Domain ◽  
Subunit Vaccines

The development of an effective vaccine that can be rapidly manufactured and distributed worldwide is necessary to mitigate the devastating health and economic impacts of pandemics like COVID-19. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, which mediates host cell entry of the virus, is an appealing antigen for subunit vaccines because it is easy to manufacture and highly stable. Moreover, RBD is a target for neutralizing antibodies and robust cytotoxic T lymphocyte responses. Unfortunately, RBD is poorly immunogenic. While most subunit vaccines are commonly formulated with adjuvants to enhance their immunogenicity, most common adjuvant combinations have not been sufficient to improve RBD immunogenicity and none have afforded neutralizing responses in a single-dose RBD vaccine. Here we show that sustained delivery of an RBD subunit vaccine in an injectable hydrogel depot formulation increases total anti-RBD IgG titers compared to bolus administration of the same vaccines. Notably, a SARS-CoV-2 spike-pseudotyped lentivirus neutralization assay revealed neutralizing antibodies in all mice after a single hydrogel vaccine administration comprising clinically-approved adjuvants Alum and CpG. Together, these results suggest that extending the exposure to RBD subunit vaccines significantly enhances the immunogenicity of RBD and induces neutralizing humoral immunity following a single immunization.

scholarly journals Evaluation of a subunit vaccine candidate (Biotech Vac Cox) against Eimeria spp. in broiler chickens

2021 ◽  
pp. 101329
Author(s):  
Emanuel Gumina ◽  
Jeffrey W. Hall ◽  
Bruno Vecchi ◽  
Xochitl Hernandez-Velasco ◽  
Brett Lumpkins ◽  
...  
Keyword(s):  
Broiler Chickens ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Eimeria Spp ◽  
A Subunit

scholarly journals Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 302 ◽  
Author(s):  
Anthony C. Ike ◽  
Chisom J. Onu ◽  
Chukwuebuka M. Ononugbo ◽  
Eleazar E. Reward ◽  
Sophia O. Muo
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infections ◽  
Recombinant Dna ◽  
Vaccine Development ◽  
The Body ◽  
Effective Vaccine ◽  
Subunit Vaccines ◽  
Simplex Virus ◽  
Hsv Infections

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

Nanovaccine: A hope to triumph the battle against novel Coronavirus disease 2019 (COVID-19)

2021 ◽  
Vol 15 ◽  
Author(s):  
Anurag Singh ◽  
Anand Maurya ◽  
Gaurav Mishra ◽  
Rajendra Awasthi ◽  
Kamal Dua ◽  
...  
Keyword(s):  
Subunit Vaccine ◽  
Goblet Cells ◽  
Spike Protein ◽  
Effective Vaccine ◽  
The Novel ◽  
Infection Site ◽  
Peptide Vaccines ◽  
Ciliated Cells ◽  
Novel Coronavirus ◽  
Major Target

Background: The novel coronavirus 2019 (COVID-19) infection has caused the global emergence of coronavirus in humans during the last 12 months. Till May 11, 2021, the confirmed global COVID-19 cases and deaths reached 158551526 and 3296855, respectively. Methods: Goblet cells and ciliated cells in the nose act as the initial infection site of SARS-CoV-2. Thus, mucus immunity is important to protect from infection. The outburst of SARS-CoV-2 infection can be halted only when an effective vaccine will be developed. Results: Globally, over 100 different vaccines are under investigation, including DNA vaccines, RNA vaccines, inactivated virus vaccines, adenovirus-based vaccines, recombinant/ subunit protein vaccines, peptide vaccines, and virus-like particles etc. Inactivated virus vaccines and mRNA, and adenovirus-based vaccines have moved fast into clinical trials. Conclusion: : Vaccines containing spike protein of SARS-CoV as subunit could effectively prevent binding of coronavirus to the host cell and membrane fusion. Thus, spike protein can be used as a major target for subunit vaccine preparation.

scholarly journals A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joshua S. Woodworth ◽  
Helena Strand Clemmensen ◽  
Hannah Battey ◽  
Karin Dijkman ◽  
Thomas Lindenstrøm ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Subunit Vaccine ◽  
Clinical Results ◽  
Cross Reactivity ◽  
Bacillus Calmette Guerin ◽  
Adaptive Responses ◽  
Vaccine Strategy ◽  
Subunit Vaccines ◽  
Protective Antigens

AbstractGiven the encouraging clinical results of both candidate subunit vaccines and revaccination with Bacillus Calmette-Guérin (BCG) against tuberculosis (TB), there is support for combining BCG and subunit vaccination for increased efficacy. BCG and Mycobacterium tuberculosis (Mtb) share ~98% of their genome and current subunit vaccines are almost exclusively designed as BCG boosters. The goal of this study is to design a TB subunit vaccine composed of antigens not shared with BCG and explore the advantages of this design in a BCG + subunit co-administration vaccine strategy. Eight protective antigens are selected to create an Mtb-specific subunit vaccine, named H107. Whereas traditional vaccines containing BCG-shared antigens exhibit in vivo cross-reactivity to BCG, H107 shows no cross-reactivity and does not inhibit BCG colonization. Instead, co-administering H107 with BCG leads to increased adaptive responses against both H107 and BCG. Importantly, rather than expanding BCG-primed T cells, H107 broadens the overall vaccine repertoire with new T cell clones and introduces ‘adjuvant-imprinted’ qualities including Th17 responses and less-differentiated Th1 cells. Collectively, these features of H107 are associated with a substantial increase in long-term protection.

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