A fowl adenovirus serotype 4 (FAdV-4) Fiber2 subunit vaccine candidate provides complete protection against challenge with virulent FAdV-4 strain in chickens

Yin, Dongmei; He, Liangmei; Zhu, Erpeng; Fang, Tian; Yue, Jun; Wen, Ming; KaiGong, Wang; Cheng, Zhentao

doi:10.1016/j.vetmic.2021.109250

Cited by 23 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results indicated that fiber-2 (50 µg/bird) and fiber-1 (100 µg/bird) could induce complete protection, while protection of the L1-hexon and penton bases could induce considerable protection at high dosages but not completely. The good immunogenicity of prokaryotic expressed fiber-2 was further confirmed when fiber-2 was coupled with different adjuvants, such as FCA ( 39 ), Montanide ISA 71VG ( 40 ), and Sigma adjuvant ( 41 ), respectively. However, fiber-1 showed better protection than fiber-2 when expressed in a eukaryotic system, although the protection rates of both fiber-1 and fiber-2 were higher than those of the penton base ( 42 ).…”

Section: Introductionmentioning

confidence: 81%

See 1 more Smart Citation

Advances in Vaccine Development of the Emerging Novel Genotype Fowl Adenovirus 4

et al. 2022

View full text Add to dashboard Cite

Fowl adenovirus (FAdV) was first reported in Angara Goth, Pakistan, in 1987. For this reason, it is also known as “Angara disease.” It was later reported in China, Japan, South Korea, India, the United States, Canada, and other countries and regions, causing huge economic losses in the poultry industry worldwide. Notably, since June 2015, a natural outbreak of severe hydropericardium hepatitis syndrome (HHS), associated with a hypervirulent novel genotype FAdV-4 infection, has emerged in most provinces of China. The novel virus FAdV-4 spread rapidly and induced a 30-100% mortality rate, causing huge economic losses and threatening the green and healthy poultry breeding industry. Vaccines against FAdV-4, especially the emerging novel genotype, play a critical role and will be the most efficient tool for preventing and controlling HHS. Various types of FAdV-4 vaccines have been developed and evaluated, such as inactivated, live-attenuated, subunit, and combined vaccines. They have made great contributions to the control of HHS, but the details of cross-protection within FAdVs and the immunogenicity of different vaccines require further investigation. This review highlights the recent advances in developing the FAdV-4 vaccine and promising new vaccines for future research.

show abstract

Section: Introductionmentioning

confidence: 81%

“…In addition, several studies have been conducted to obtain many results. Yin et al constructed a pVAX1-Fiber2 DNA vaccine, but the protection was also insufficient (60%) for the novel genotype FAdV-4, and the above studies require further optimization ( 41 ). Nevertheless, many improvements have achieved good results.…”

Section: Introductionmentioning

confidence: 99%

Advances in Vaccine Development of the Emerging Novel Genotype Fowl Adenovirus 4

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Currently, vaccination is the primary strategy for preventing and controlling HHS. Immunization with inactivated liver homogenate ( 14 , 44 ), attenuated vaccines ( 32 ), live vaccines ( 45 ), and recombinant antigen vaccines ( 46 ) protects against infection. Inactivated vaccines have a lower risk of virulence reversion than live vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Several latest studies have shown that the pathogenicity of China's newly emerged highly pathogenic FAdV-4 is closely related to the Fiber2 gene (29)(30)(31). The Fiber2 protein-based subunit vaccine offered protection against the FAdV-4 challenge (32).…”

Section: Introductionmentioning

confidence: 99%

Probiotics Surface-Delivering Fiber2 Protein of Fowl Adenovirus 4 Stimulate Protective Immunity Against Hepatitis-Hydropericardium Syndrome in Chickens

et al. 2022

View full text Add to dashboard Cite

Background and ObjectivesHepatitis-hydropericardium syndrome (HHS) caused by Fowl adenoviruses serotype 4 (FAdV-4) leads to severe economic losses to the poultry industry. Although various vaccines are available, vaccines that effectively stimulate intestinal mucosal immunity are still deficient. In the present study, novel probiotics that surface-deliver Fiber2 protein, the major virulence determiner and efficient immunogen for FAdV-4, were explored to prevent this fecal–oral-transmitted virus, and the induced protective immunity was evaluated after oral immunization.MethodsThe probiotic Enterococcus faecalis strain MDXEF-1 and Lactococcus lactis NZ9000 were used as host strains to deliver surface-anchoring Fiber2 protein of FAdV-4. Then the constructed live recombinant bacteria were orally vaccinated thrice with chickens at intervals of 2 weeks. Following each immunization, immunoglobulin G (IgG) in sera, secretory immunoglobulin A (sIgA) in jejunum lavage, immune-related cytokines, and T-cell proliferation were detected. Following challenge with the highly virulent FAdV-4, the protective effects of the probiotics surface-delivering Fiber2 protein were evaluated by verifying inflammatory factors, viral load, liver function, and survival rate.ResultsThe results demonstrated that probiotics surface-delivering Fiber2 protein stimulated humoral and intestinal mucosal immune responses in chickens, shown by high levels of sIgA and IgG antibodies, substantial rise in mRNA levels of cytokines, increased proliferative ability of T cells in peripheral blood, improved liver function, and reduced viral load in liver. Accordingly, adequate protection against homologous challenges and a significant increase in the overall survival rate were observed. Notably, chickens orally immunized with E. faecalis/DCpep-Fiber2-CWA were completely protected from the FAdV-4 challenge, which is better than L. lactis/DCpep-Fiber2-CWA.ConclusionThe recombinant probiotics surface-expressing Fiber2 protein could evoke remarkable humoral and cellular immune responses, relieve injury, and functionally damage target organs. The current study indicates a promising method used for preventing FAdV-4 infection in chickens.

show abstract

“…Despite the worldwide occurrence of FAdVs and their growing economic impact, the lack of broadly protective and commercially accessible immunization strategies has led to extensive investigations on experimental vaccine antigens ( 3 – 7 ). In regards to subunit vaccines, the fiber protein, one of the major structural capsid components and surface antigens, has proven highly effective against HHS- and IBH-causing strains ( 8 – 15 ). Recently, the novel concept of chimeric fiber protein (crecFib) was formulated by designing a recombinant construct mimicking the full fiber structure incorporating epitopes from two distinct serotypes, in order to protect chickens from the diverse etiology of IBH ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Local cellular immune response plays a key role in protecting chickens against hepatitis-hydropericardium syndrome (HHS) by vaccination with a recombinant fowl adenovirus (FAdV) chimeric fiber protein

et al. 2022

View full text Add to dashboard Cite

Fowl adenovirus (FAdV)-induced diseases hepatitis-hydropericardium syndrome (HHS) and inclusion body hepatitis (IBH) have been affecting the poultry industry with increasing severity in the last two decades. Recently, a subunit vaccine based on a chimeric fiber protein with epitopes from different fowl adenovirus serotypes (named crecFib-4/11) has been shown to confer simultaneous protection against both HHS and IBH. However, the underlying immune mechanisms in chickens are still enigmatic, especially because of frequently absent neutralizing response despite high levels of protection. In this study, we investigated the kinetics of the humoral and cellular immune responses in specific pathogen-free chickens after vaccination with crecFib-4/11 and/or challenge with a HHS-causing strain, on a systemic level, as well as locally in target and lymphoid organs. The humoral response was assessed via enzyme-linked immunosorbent assay (ELISA) and virus neutralization test in serum, while the cellular immune response was determined by phenotyping using flow cytometry. Although vaccination induced serum antibodies, as confirmed by ELISA, such antibodies exhibited no pre-challenge neutralizing activity against FAdV-4. Nevertheless, immunized birds experienced a significant B cell increase in the liver upon challenge, remaining high throughout the experiment. Furthermore, vaccination stimulated the proliferation of cytotoxic T lymphocytes, with earlier circulation in the blood compared to the challenge control and subsequent increase in liver and spleen. Overall, these findings imply that protection of chickens from HHS after crecFib-4/11 vaccination relies on a prominent local immune response in the target organs, instead of circulating neutralizing antibodies.

show abstract

A fowl adenovirus serotype 4 (FAdV-4) Fiber2 subunit vaccine candidate provides complete protection against challenge with virulent FAdV-4 strain in chickens

Cited by 23 publications

References 31 publications

Advances in Vaccine Development of the Emerging Novel Genotype Fowl Adenovirus 4

Advances in Vaccine Development of the Emerging Novel Genotype Fowl Adenovirus 4

Probiotics Surface-Delivering Fiber2 Protein of Fowl Adenovirus 4 Stimulate Protective Immunity Against Hepatitis-Hydropericardium Syndrome in Chickens

Local cellular immune response plays a key role in protecting chickens against hepatitis-hydropericardium syndrome (HHS) by vaccination with a recombinant fowl adenovirus (FAdV) chimeric fiber protein

Contact Info

Product

Resources

About