Enhancing Protective Efficacy of Poultry Vaccines through Targeted Delivery of Antigens to Antigen-Presenting Cells

Avian viral diseases including avian influenza, Marek’s disease and Newcastle disease are detrimental to economies around the world that depend on the poultry trade. A significant zoonotic threat is also posed by avian influenza viruses. Vaccination is an important and widely used method for controlling these poultry diseases. However, the current vaccines do not provide full protection or sterile immunity. Hence, there is a need to develop improved vaccines. The major aim of developing improved vaccines is to induce strong and specific humoral and cellular immunity in vaccinated animals. One strategy used to enhance the immunogenicity of vaccines is the selective delivery of protective antigens to antigen-presenting cells (APCs) including dendritic cells, macrophages and B cells. APCs have a central role in the initiation and maintenance of immune responses through their ability to capture, process and present antigens to T and B cells. Vaccine technology that selectively targets APCs has been achieved by coupling antigens to monoclonal antibodies or ligands that are targeted by APCs. The aim of this review is to discuss existing strategies of selective delivery of antigens to APCs for effective vaccine development in poultry.

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

Scientific Reports ◽

10.1038/s41598-021-88413-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Han Lei ◽

Xin Lu ◽

Shuangqin Li ◽

Yi Ren

Keyword(s):

Saccharomyces Cerevisiae ◽

Avian Influenza ◽

Oral Administration ◽

Large Scale ◽

Vaccine Development ◽

Protective Efficacy ◽

Oral Vaccine ◽

Influenza Viruses ◽

Effective Vaccine ◽

Live Virus

AbstractA 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.

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

10.21203/rs.3.rs-33780/v1 ◽

2020 ◽

Author(s):

Han Lei ◽

Qianhong Cen ◽

Tong Gao ◽

Yi Ren ◽

Xin Lu

Keyword(s):

Saccharomyces Cerevisiae ◽

Avian Influenza ◽

Oral Administration ◽

Vaccine Development ◽

Protective Efficacy ◽

Oral Vaccine ◽

Influenza Viruses ◽

Cross Protection ◽

Effective Vaccine ◽

Live Virus

Abstract BackgroundA 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 injection administration with a S. cerevisiae-based vaccine (EBY100/pYD1-HA) was protective against homologous H5N1 virus in a mouse model. Due to the diameter of S. cerevisiae is around 10 μm which results in a severe inflammation by injection route, therefore, oral administration is a more suitable approach for EBY100/pYD1-HA conferring cross-protection in poultry. ResultsWe extended our work by evaluating the immunogenicity and cross-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 complete cross-protection against different H5N1 viruses challenge. ConclusionsThese findings suggest 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 drawbacks of conventional injection route. Importantly, this platform will be able to provide opportunities for broader applications in poultry during HPAI A (H5N1) outbreaks.

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T-cells of transgenic mice in which B-cells act as antigen presenting cells (APC) exhibit a unique immune profile and do not induce inflammation

Immunology Letters ◽

10.1016/s0165-2478(97)87914-x ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 269

Author(s):

A de Vos

Keyword(s):

T Cells ◽

B Cells ◽

Transgenic Mice ◽

Antigen Presenting Cells ◽

Immune Profile ◽

Antigen Presenting

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Glycine at Position 622 in PB1 Contributes to the Virulence of H5N1 Avian Influenza Virus in Mice

Journal of Virology ◽

10.1128/jvi.02387-15 ◽

2015 ◽

Vol 90 (4) ◽

pp. 1872-1879 ◽

Cited By ~ 12

Author(s):

Xiaoxiao Feng ◽

Zeng Wang ◽

Jianzhong Shi ◽

Guohua Deng ◽

Huihui Kong ◽

...

Keyword(s):

Avian Influenza ◽

Aspartic Acid ◽

H5n1 Virus ◽

Genetic Basis ◽

Vaccine Development ◽

Influenza Viruses ◽

Avian Influenza Viruses ◽

Live Attenuated Vaccine ◽

H5n1 Influenza ◽

H5n1 Avian Influenza

ABSTRACTWe isolated two H5N1 viruses, A/duck/Hunan/S4020/2008 (DK/08) and A/chicken/Guangxi/S2039/2009 (CK/09), from live-bird markets during routine surveillance and found that these two viruses are genetically similar but differ in their replication and virulence in mice. The CK/09 virus is lethal for mice with a 50% mouse lethal dose (MLD50) of 1.6 log1050% egg infectious doses (EID50), whereas the DK/08 virus is nonpathogenic for mice with an MLD50value of 6.2 log10EID50. We explored the genetic basis of the virulence difference of these two viruses by generating a series of reassortant viruses and mutants in the lethal virus CK/09 background and evaluating their virulence in mice. We found that the PB1 gene of the DK/08 virus dramatically attenuated the virulence of the CK/09 virus and that the amino acid at position 622 in PB1 made an important contribution. We further demonstrated that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impaired the binding of PB1 to viral RNA, thereby dramatically decreasing the polymerase activity and attenuating H5N1 virus virulence in mice. Our results identify a novel virulence-related marker of H5N1 influenza viruses and provide a new target for live attenuated vaccine development.IMPORTANCEH5N1 avian influenza viruses have caused the deaths of nearly 60% of the humans that they have infected since 1997 and clearly represent a threat to public health. A thorough understanding of the genetic basis of virulence determinants will provide important insights for antiviral drug and live attenuated vaccine development. Several virulence-related markers in the PB2, PA, M1, and NS1 proteins of H5N1 viruses have been identified. In this study, we isolated two H5N1 avian influenza viruses that are genetically similar but differ in their virulence in mice, and we identified a new virulence-related marker in the PB1 gene. We found that the mutation of glycine (G) to aspartic acid (D) at position 622 in PB1 partially impairs the binding of PB1 to viral RNA, thereby attenuating H5N1 virus virulence in mice. This newly identified virulence-related marker could be applied to the development of live attenuated vaccines against H5N1 influenza.

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Role of B cells as antigen-presenting cells in vivo revisited: antigen-specific B cells are essential for T cell expansion in lymph nodes and for systemic T cell responses to low antigen concentrations

International Immunology ◽

10.1093/intimm/13.12.1583 ◽

2001 ◽

Vol 13 (12) ◽

pp. 1583-1593 ◽

Cited By ~ 113

Author(s):

Amariliz Rivera ◽

Chiann-Chyi Chen ◽

Naomi Ron ◽

Joseph P. Dougherty ◽

Yacov Ron

Keyword(s):

T Cell ◽

B Cells ◽

Lymph Nodes ◽

Cell Expansion ◽

T Cell Responses ◽

Antigen Presenting Cells ◽

Cell Responses ◽

Antigen Presenting

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Follicular dendritic cells help resting B cells to become effective antigen-presenting cells: induction of B7/BB1 and upregulation of major histocompatibility complex class II molecules.

Journal of Experimental Medicine ◽

10.1084/jem.178.6.2055 ◽

1993 ◽

Vol 178 (6) ◽

pp. 2055-2066 ◽

Cited By ~ 59

Author(s):

M H Kosco-Vilbois ◽

D Gray ◽

D Scheidegger ◽

M Julius

Keyword(s):

Dendritic Cells ◽

Major Histocompatibility Complex ◽

B Cells ◽

Major Histocompatibility Complex Class ◽

B Cell ◽

Antigen Presenting Cells ◽

Follicular Dendritic Cells ◽

Complex Class ◽

Histocompatibility Complex ◽

Antigen Presenting

This study was designed to investigate whether follicular dendritic cells (FDC) can activate B cells to a state in which they can function as effective antigen-presenting cells (APC). High buoyant density (i.e., resting) B cells specific for 2,4-dinitro-fluorobenzene (DNP) were incubated with DNP-ovalbumin (OVA) bearing FDC, after which their capacity to process and present to an OVA-specific T cell clone was assessed. The efficacies of alternative sources of antigen and activation signals in the induction of B cell APC function were compared with those provided by FDC. Only FDC and Sepharose beads coated with anti-immunoglobulin (Ig)kappa monoclonal antibody provided the necessary stimulus. FDC carrying inappropriate antigens also induced B cell APC function in the presence of exogenous DNP-OVA. However, in circumstances where soluble DNP-OVA was limiting, FDC bearing complexes containing DNP, which could crosslink B cell Ig receptors, induced the most potent APC function. Analysis by flow cytometry revealed that within 24 h of coculture with FDC, a significant percentage of B cells increased in size and expressed higher levels of major histocompatibility complex class II. By 48 h, an upregulation of the costimulatory molecule, B7/BB1, occurred, but only when exposed to the FDC bearing DNP. Taken together, the results demonstrate that FDC have the capacity to activate resting B cells to a state in which they can function as APC for T cells. The stimuli that FDC provide may include: (a) an antigen-dependent signal that influences the upregulation of B7/BB1; and (b) possibly a signal independent of crosslinking mIg that results in Ig internalization. The relevance of these findings to the formation of germinal centers and maintenance of the humoral response is discussed.

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Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo

Journal of Experimental Medicine ◽

10.1084/jem.187.10.1611 ◽

1998 ◽

Vol 187 (10) ◽

pp. 1611-1621 ◽

Cited By ~ 67

Author(s):

Sarah E. Townsend ◽

Christopher C. Goodnow

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Antigen Presentation ◽

Cell Fate ◽

T Cell Activation ◽

Cell Activation ◽

Antigen Presenting Cells ◽

Antigen Presenting

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4+ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.

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