Immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant Gp96 against rabies

Abstract

Rabies, a zoonotic disease, causes > 55,000 human deaths globally and results in at least 500 million dollars in losses every year. The currently available rabies vaccines are mainly inactivated and attenuated vaccines, which have been linked with clinical diseases in animals. Thus, a rabies vaccine with high safety and efficacy is urgently needed. Peptide vaccines are known for their low cost, simple production procedures and high safety. Therefore, in this study, we examined the efficacy of multi-epitope-based vaccine candidates against rabies virus. The ability of various peptides to induce epitope-specific responses was examined, and the two peptides that possessed the highest antigenicity and conservation, i.e., AR16 and hPAB, were coated with adjuvant canine-Gp96 and used to prepare vaccines. The peptides were prepared as an emulsion of oil in water (O/W) to create three batches of bivalent vaccine products. The vaccine candidates possessed high safety. Virus neutralizing antibodies were detected on the day 14 after the first immunization in mice and beagles, reaching 5-6 IU/mL in mice and 7-9 IU/mL in beagles by day 28. The protective efficacy of the vaccine candidates was about 70%-80% in mice challenged by a virulent strain of rabies virus. Thus, a novel multi-epitope-based rabies vaccine with Gp96 as an adjuvant was developed and validated in mice and dogs. Our results suggest that synthetic peptides hold promise for the development of novel vaccines against rabies.

Heat Shock Proteins 90 kDa: Immunomodulators and Adjuvants in Vaccine Design Against Infectious Diseases

“…It is necessary to formulate novel strategies to develop non-toxic adjuvants and less immunogenic vaccine delivery carriers to prevent various animal diseases. Several host-, pathogen-, and non-pathogenderived Hsp90 were exploited as adjuvants with promising results (Echeverría et al, 2006;Mohit et al, 2011;Wang S. et al, 2011;Ju et al, 2014;Albarracín et al, 2015;Niu et al, 2016;Zhu et al, 2016;Bengoa Luoni et al, 2019;Sánchez López et al, 2019). This review presents a comprehensive revision of the adjuvant properties of Hsp90s and their potential application in the adjuvant design of vaccines to prevent infectious diseases.…”

Oral Immunization With a Plant HSP90-SAG1 Fusion Protein Produced in Tobacco Elicits Strong Immune Responses and Reduces Cyst Number and Clinical Signs of Toxoplasmosis in Mice

“…In fact, SAG1 immunization was always analyzed with an adjuvant to generate a strong Th1 immune response (Wang and Yin, 2014). Previous studies evaluating the adjuvant capacity of the murine heat shock protein Gp96 fused to antigenic peptides from different pathogenic viruses showed that Gp96 significantly increases the specific IgG2a/b response against the carried peptides (Chen et al, 2013;Ju et al, 2014;Niu et al, 2016). In addition, some authors showed that while a high immune response occurs against the fused antigen of interest, they did not observe an immune response against Gp96 or HSP90.…”

New Rabies Vaccines for Use in Humans

“…A plethora of novel rabies vaccines based mainly on the viral glycoprotein have been tested in animals using mainly PEP regimens. Many of them such as a yeast-derived protein vaccine [28] or peptide vaccines showed lack of complete efficacy and are thus unlikely to progress to clinical trials [29,30]. Others, such as genetically engineered live attenuated rabies viruses, which were shown in animals to be safe and efficacious [31,32] are unlikely to gain public approval.…”