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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.
Highlights
The emergence and spread of highly pathogenic avian influenza (HPAI) A (H5N1) viruses have fueled concerns of a potential zoonotic pandemic originating in poultry[1], and spurred efforts towards developing vaccines against A (H5N1) influenza viruses and improving vaccine production m ethods[2]
Western blot analysis was performed to determine the expression of HA protein, the expected band corresponding to 75 kDa was observed in the lysates of EBY100/pYD1-HA (Fig. 1a, Lane 1), which consisted of Aga[2] (10 kDa) and HA protein (65 kDa), whereas it was absent in the lysates of EBY100/pYD1 (Fig. 1a, Lane 2)
When the concentration of antibody was increased beyond this point, the optical density was relatively stable, which suggested that 5 O D600nm of EBY100/pYD1HA expressing HA protein was at its saturation limit at 60 μg/mL compared with the known concentration of purified HA protein
Summary
The emergence and spread of highly pathogenic avian influenza (HPAI) A (H5N1) viruses have fueled concerns of a potential zoonotic pandemic originating in poultry[1], and spurred efforts towards developing vaccines against A (H5N1) influenza viruses and improving vaccine production m ethods[2]. The current licensed vaccines, including adjuvanted formulations, predominately include inactivated whole avian influenza H5N1 and are available for the control of outbreaks in p oultry[3] These vaccines have limitations since they require intramuscular injection, and the biosecurity of these vaccines has not been fully e lucidated[4]. Included in the list of alternative strategies are the recombinant yeast-based A (H5N1) vaccines, which are promising candidates that meet the requirement of vaccine production in a timely manner and can induce robust protective immunity against A(H5N1) virus infection[15]. Chickens are the primary model for studies of pathogenicity and vaccine efficacy studies for poultry[21] To address this issue, we hypothesize that oral vaccination with unadjuvanted EBY100/pYD1-HA can produce protective immunity in the chicken model and can be considered an effective platform for the development of an influenza A (H5N1) vaccine for the mass vaccination of poultry
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