Oral immunization of recombinant Saccharomyces cerevisiae expressing fiber-2 of fowl adenovirus serotype 4 induces protective immunity against homologous infection

Cao, Hongwei; Dai, Hua; Zhang, Han; Zhang, Huixia; Liu, Na; Feng, Zhehan; Li, Huliang; Zhao, Baiping; Zhang, Lilin; Guo, Yanyu; Huang, Jinhai; Zhang, Lei

doi:10.1016/j.vetmic.2022.109490

Cited by 10 publications

(6 citation statements)

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“…We firstly constructed a recombinant S. cerevisiae ST1814G (MATa aga1 his3Δ200 leu2Δ0 lys2Δ0 trp1Δ63 ura3Δ0 met15Δ0) strain expressing 17-484 amino acids of H5HA protein excluding the signaling peptides, which was integrated into the S. cerevisiae chromosome IV according to the methods as our previous studies ( 28 ), and the HA protein was expressed correctly as expected as shown in Figure 1A . This genetically engineered yeast strain was used as recombinant protein vaccine (ST1814G/H5HA) and it also serves as yeast chassis for our next protein-nucleic acid combined vaccine.…”

Section: Resultsmentioning

confidence: 99%

Hemagglutinin expressed by yeast reshapes immune microenvironment and gut microbiota to trigger diverse anti-infection response in infected birds

Xie

Zhang

et al. 2023

Front. Immunol.

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IntroductionThe H5N8 influenza virus is a highly pathogenic pathogen for poultry and human. Vaccination is the most effective method to control the spread of the virus right now. The traditional inactivated vaccine, though well developed and used widely, is laborious during application and more interests are stimulated in developing alternative approaches.MethodsIn this study, we developed three hemagglutinin (HA) gene-based yeast vaccine. In order to explore the protective efficacy of the vaccines, the gene expression level in the bursa of Fabricius and the structure of intestinal microflora in immunized animals were analyzed by RNA seq and 16SrRNA sequencing, and the regulatory mechanism of yeast vaccine was evaluated.ResultsAll of these vaccines elicited the humoral immunity, inhibited viral load in the chicken tissues, and provided partial protective efficacy due to the high dose of the H5N8 virus. Molecular mechanism studies suggested that, compared to the traditional inactivated vaccine, our engineered yeast vaccine reshaped the immune cell microenvironment in bursa of Fabricius to promote the defense and immune responses. Analysis of gut microbiota further suggested that oral administration of engineered ST1814G/H5HA yeast vaccine increased the diversity of gut microbiota and the increasement of Reuteri and Muciniphila might benefit the recovery from influenza virus infection. These results provide strong evidence for further clinical use of these engineered yeast vaccine in poultry.

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Section: Resultsmentioning

confidence: 99%

Hemagglutinin expressed by yeast reshapes immune microenvironment and gut microbiota to trigger diverse anti-infection response in infected birds

Xie

Zhang

et al. 2023

Front. Immunol.

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“…However, the intrinsic serotype-specifc neutralizing activity of Fiber limits the application and efcacy of fber-based vaccines [36]. For controlling HHS, vaccine candidates based on inactivated FAdV-4 or Fiber-2 protein have been generated and proven to be efcient [20,22,24,[37][38][39][40][41][42]. In order to develop potential vaccines providing broad crossprotection against HHS and IBH caused by various serotypes of FAdV, several bivalent vaccine candidates against both FAdV-4 and FAdV-8b, FAdV-8a and FAdV-8b, or FAdV FAdV-4 possesses two fber genes that encode Fiber-1 and Fiber-2 proteins.…”

Section: Discussionmentioning

confidence: 99%

“…In order to develop potential vaccines providing broad crossprotection against HHS and IBH caused by various serotypes of FAdV, several bivalent vaccine candidates against both FAdV-4 and FAdV-8b, FAdV-8a and FAdV-8b, or FAdV FAdV-4 possesses two fber genes that encode Fiber-1 and Fiber-2 proteins. Fiber-1 plays crucial role in mediating FAdV-4 infection and Fiber-2 plays important roles in inducing protective immune responses [37,43,44]. FAdV-8b and FAdV-11 only have one fber gene in their genomes.…”

Section: Discussionmentioning

confidence: 99%

An Inactivated Novel Trivalent Vaccine Provides Complete Protection against FAdV-4 Causing Hepatitis-Hydropericardium Syndrome and FAdV-8b/-11 Causing Inclusion Body Hepatitis

Song

Zhao

Song

et al. 2023

Transboundary and Emerging Diseases

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Outbreaks of hepatitis-hydropericardium syndrome (HHS) caused by fowl adenovirus serotype 4 (FAdV-4) and inclusion body hepatitis (IBH) related to FAdV-8b and FAdV-11 have been increased in chickens in China since 2015. Clinical concurrent infections of FAdV-4, FAdV-8b, and FAdV-11 are quite common, yet there are no commercially available trivalent vaccines against infection by these three serotypes. In our previous study, a bivalent vaccine based on a recombinant FAdV-4, of which fiber-1 was replaced with the fiber of FAdV-8b, has been developed. In this study, a novel recombinant rFAdV-4-fiber/8b + 11 was constructed by inserting FAdV-11 fiber gene into the 1966-bp deletion region of rFAdV-4-fiber/8b genome. The in vitro replication ability of the rFAdV-4-fiber/8b + 11 was similar to the parental FAdV-4. One dose immunization with the inactivated rFAdV-4-fiber/8b + 11 vaccine generated robust immune responses against FAdV-4, FAdV-8b, and FAdV-11, and provided efficient clinical protection against FAdV-4, FAdV-8b, and FAdV-11 challenge. This study provides a novel strategy for developing potential trivalent vaccines for the prevention and control of HHS and IBH.

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“…However, in this study, the molecular weight of VP2 was larger (~70 kDa) than expected (~48.3 kDa), which may be related to N-glycosylation during the post-translational modification in yeast. A previous study using yeast to express Fiber-2 of FAdV-4 also found that the recombinant protein was enlarged by glycosylation [ 28 ]. Several studies drew different conclusions on whether post-translational N-glycosylation in S. cerevisiae has an effect on the recombinant protein.…”

Section: Discussionmentioning

confidence: 99%

“…The specific IgG and sIgA were determined via ELISA in the serum and feces of mice, respectively, as previously described [ 28 ]. Briefly, the 96-well microplates were coated with purified VP2 [5 μg/mL (100 μL/well)] at 4 °C overnight.…”

Section: Methodsmentioning

confidence: 99%

Oral Immunization with Recombinant Saccharomyces cerevisiae Expressing Viral Capsid Protein 2 of Infectious Bursal Disease Virus Induces Unique Specific Antibodies and Protective Immunity

Li,

Hua,

et al. 2023

Vaccines

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Infectious bursal disease (IBD), as a highly infectious immunosuppressive disease, causes severe economic losses in the poultry industry worldwide. Saccharomyces cerevisiae is an appealing vehicle used in oral vaccine formulations to safely and effectively deliver heterologous antigens. It can elicit systemic and mucosal responses. This study aims to explore the potential as oral an vaccine for S. cerevisiae expressing the capsid protein VP2 of IBDV. We constructed the recombinant S. cerevisiae, demonstrated that VP2 was displayed on the cell surface and had high immunoreactivity. By using the live ST1814G/Aga2-VP2 strain to immunize the mice, the results showed that recombinant S. cerevisiae significantly increased specific IgG and sIgA antibody titers, indicating the potential efficacy of vaccine-induced protection. These results suggested that the VP2 protein-expressing recombinant S. cerevisiae strain was a promising candidate oral subunit vaccine to prevent IBDV infection.

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Oral immunization of recombinant Saccharomyces cerevisiae expressing fiber-2 of fowl adenovirus serotype 4 induces protective immunity against homologous infection

Cited by 10 publications

References 61 publications

Hemagglutinin expressed by yeast reshapes immune microenvironment and gut microbiota to trigger diverse anti-infection response in infected birds

Hemagglutinin expressed by yeast reshapes immune microenvironment and gut microbiota to trigger diverse anti-infection response in infected birds

An Inactivated Novel Trivalent Vaccine Provides Complete Protection against FAdV-4 Causing Hepatitis-Hydropericardium Syndrome and FAdV-8b/-11 Causing Inclusion Body Hepatitis

Oral Immunization with Recombinant Saccharomyces cerevisiae Expressing Viral Capsid Protein 2 of Infectious Bursal Disease Virus Induces Unique Specific Antibodies and Protective Immunity

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