Rabies vaccine development by expression of recombinant viral glycoprotein

Astray, Renato Mancini; Jorge, Soraia Attie Calil; Pereira, Carlos Augusto

doi:10.1007/s00705-016-3128-9

Cited by 34 publications

(23 citation statements)

References 124 publications

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“…Hence, developing a novel, affordable, and long-acting rabies vaccine is urgently needed. As the major protective antigen of RABV, G protein is usually selected for novel rabies vaccine designation (Astray et al, 2017). At present, the recombinant vaccines based on poxvirus, adenovirus and parainfluenza expressing G protein of RABV have been studied, some of which have been successfully used for rabies prevention (Yarosh et al, 1996;Chen et al, 2013;Stading et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human Adenovirus Type 5 Co-expressing RABV G and SFTSV Gn Induces Protective Immunity Against Rabies Virus and Severe Fever With Thrombocytopenia Syndrome Virus in Mice

et al. 2020

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Both severe fever with thrombocytopenia syndrome (SFTS) and rabies are severe zoonotic diseases. As co-hosts of rabies virus (RABV) and SFTS virus (SFTSV), dogs and cats could not only be infected but also transmit the virus to human. Hence, developing a bivalent vaccine against both SFTS and rabies is urgently needed. In this study, we generated a recombinant replication-deficient human adenovirus type 5 (Ad5) co-expressing RABV G and SFTSV Gn (Ad5-G-Gn) and evaluated its immunogenicity and efficacy in mice. Ad5-G-Gn immunization activated more dendritic cells (DCs) and B cells in lymph nodes (LNs) and induced Th1-/Th2-mediated responses in splenocytes, leading to robust production of neutralizing antibodies against SFTSV and RABV. In addition, single dose of Ad5-G-Gn conferred mice complete protection against lethal RABV challenge and significantly reduced splenic SFTS viral load. Therefore, our data support further development of Ad5-G-Gn as a potential bivalent vaccine candidate against SFTS and rabies for dog and cat use.

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Section: Discussionmentioning

confidence: 99%

Recombinant Human Adenovirus Type 5 Co-expressing RABV G and SFTSV Gn Induces Protective Immunity Against Rabies Virus and Severe Fever With Thrombocytopenia Syndrome Virus in Mice

et al. 2020

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“…Of these, the envelope glycoprotein acts as an antigen to induce virus-neutralizing antibodies, which have been shown to be protective in animal challenge models [16]. Recombinant technology has been applied to the expression of glycoprotein in a variety of cell systems including mammalian cells (Vero cells, human embryonic kidney cells, baby hamster kidney cells, and Chinese hamster ovary cells), insect cells, yeasts, and plants [17]. All these systems require extensive processing of the expressed protein, with purification and additional postprocessing steps, which, together with additional requirements for adjuvantation, may make them economically nonviable.…”

Section: Innovative Approaches With Recombinant Technologymentioning

confidence: 99%

Advances in RNA Vaccines for Preventive Indications: A Case Study of a Vaccine against Rabies

2019

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: There is a global need for effective and affordable rabies vaccines, which is unmet by current vaccines due to limitations in their production capacities, required administration schedules, storage requirements, and cost. Many different experimental approaches previously used for bacterial and viral vaccines have been applied to rabies, but with variable success. One of the most promising new concepts is the use of messenger RNA (mRNA) in encoding the main rabies virus antigen, the envelope glycoprotein (RABV-G). CureVac has applied their proprietary technology platform for the production of mRNA to this problem, resulting in the rabies vaccine candidate CV7201. Following preclinical studies in mice and pigs showing that CV7201 could induce neutralizing immune responses that protected against rabies virus, different dosages and routes of administration of CV7201 were tested in a phase 1 human study. This clinical study proved that mRNA vaccination was safe and had an acceptable reactogenicity profile, but immune responses depended on the mode of administration, and they did not unequivocally support CV7201 for further development as a prophylactic vaccine with this particular formulation. Further, preclinical studies using RABV-G mRNA encapsulated in lipid nanoparticles (LNPs) showed an improved response in both mice and nonhuman primates, and these encouraging results are currently being followed up in clinical studies in humans. This review summarizes the recent advances in mRNA vaccines against rabies.

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“…Several studies show increased research activities in terms of scientific publications , patent applications and clinical trials . Different technological advances may aid the development of novel products against rabies, such as reverse genetics for the development of improved vaccines, and monoclonal antibodies to replace immunoglobulins . In the past, such technological advances indeed led to improved rabies vaccines and lowered the disease burden .…”

Section: Introductionmentioning

confidence: 99%

Quantity vs. quality: an assessment of the current pipeline for rabies

Neevel

Urias

Claassen

et al. 2020

Tropical Med Int Health

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objectives To gain insight in the potential of the current pipeline for rabies to decrease the burden of disease by evaluating its relevance to high-risk countries.methods Rabies-related patent documents and clinical trials were retrieved from Espacenet and the WHO ICTRP, respectively. Data were cleaned, modulated and categorised into a pre-defined set of indicators those were used for (statistical) analyses on the number of patent applications, patent quality and type of stakeholders involved for different geographical areas.results Analysis of 583 unique patent families applied for in the period 1954-2017 showed a steep growth in the yearly number of patent applications. A significant portion of new patent applications concern Chinese patents with relatively low quality that are filed by a dispersed group of applicants. Excluding these patents, the number of patent applications has been virtually stable over the years. A shift is seen in public stakeholders becoming more prolific as patent applicants. This shift is also reflected in clinical trials; key sponsors of clinical trials include public and private stakeholders originating from high-risk rabies countries. The majority of clinical trials investigate adjustments to existing vaccines that may improve accessibility.conclusion The results show a discrepancy between the quantity and quality of rabies patent applications that reflects national patent regulations rather than real progress in decreasing the burden of disease. This is in contrast to clinical trials, which focus on incremental innovations that are tested in clinical trials but may nevertheless have a potentially strong impact in high-risk countries.

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Rabies vaccine development by expression of recombinant viral glycoprotein

Cited by 34 publications

References 124 publications

Recombinant Human Adenovirus Type 5 Co-expressing RABV G and SFTSV Gn Induces Protective Immunity Against Rabies Virus and Severe Fever With Thrombocytopenia Syndrome Virus in Mice

Recombinant Human Adenovirus Type 5 Co-expressing RABV G and SFTSV Gn Induces Protective Immunity Against Rabies Virus and Severe Fever With Thrombocytopenia Syndrome Virus in Mice

Advances in RNA Vaccines for Preventive Indications: A Case Study of a Vaccine against Rabies

Quantity vs. quality: an assessment of the current pipeline for rabies

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