High immune efficacy against different avian influenza H5N1 viruses due to oral administration of a Saccharomyces cerevisiae-based vaccine in chickens

Abstract

A safe and effective vaccine is the best way to control large-scale highly pathogenic avian influenza virus (HPAI) A (H5N1) outbreaks. Saccharomyces cerevisiae (S. cerevisiae) is an ideal mucosal delivery vector for vaccine development, and we have previously shown that conventional administration of a S. cerevisiae-based vaccine (EBY100/pYD1-HA) via injection led to protection against the homologous H5N1 virus in a mouse model. Because the diameter of S. cerevisiae is approximately 10 μm, which results in a severe inflammation by injection route, therefore, oral administration is a more suitable approach for EBY100/pYD1-HA conferring protection in poultry. We extended our work by evaluating the immunogenicity and protective efficacy of oral vaccination with EBY100/pYD1-HA in the chicken model. Oral immunization with EBY100/pYD1-HA could induce robust serum IgG, mucosal IgA and cellular immune responses. Importantly, EBY100/pYD1-HA provided protection against challenges with a homologous and a heterologous H5N1 viruses. These findings suggest that EBY100/pYD1-HA, a promising H5N1 oral vaccine candidate, can avoid potential reassortment of other avian influenza viruses in oral administration of live virus vaccines and overcome the limitations of conventional injection routes. Importantly, this platform will be able to provide opportunities for broader applications in poultry during HPAI A (H5N1) outbreaks.

Re-evaluating efficacy of vaccines against highly pathogenic avian influenza virus in poultry: A systematic review and meta-analysis

“…After duplicate removal, 77 publications were screened, and 54 underwent full-text assessment. Ultimately, our dataset included data from 46 trials across 20 experimental studies [ [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] ], as detailed in Appendix Table 2. These trials collectively involved 863 SPF chickens.…”

Improving expression and assembly of difficult-to-express heterologous proteins in Saccharomyces cerevisiae by culturing at a sub-physiological temperature

“…S. cerevisiae has been one of the most popular heterologous expression hosts in biotechnology, and it is increasingly employed in oral vaccine development [ 10 – 16 , 37 – 41 ]. Our previous study [ 13 ] showed that the expression of LTB fused with a synthetic Dengue tetravalent antigen using S. cerevisiae was potentially useful as an oral vaccine against Dengue viruses.…”

Yeast oral vaccines against infectious diseases

“…However, many of them were also able to protect vaccinated animals against direct challenge from their target pathogen. These include candidate yeast oral vaccines against red-spotted grouper nervous necrosis virus in convict groupers ( Cho et al, 2017 ); Helicobacter pylori in mice ( Cen et al, 2021 ); cyprinid herpesvirus-3 in the common carp ( Ma et al, 2020 ); avian H5N1 influenza virus in chickens ( Lei et al, 2021b ); and white spot syndrome virus in shrimp ( Ananphongmanee et al, 2021 ), and among others. This growing list of successful animal vaccines suggests that cell-surface display is an effective technology for creating effective yeast oral vaccines.…”