Fc-Mediated E2-Dimer Subunit Vaccines of Atypical Porcine Pestivirus Induce Efficient Humoral and Cellular Immune Responses in Piglets

Congenital tremor (CT) type A-II in piglets is caused by an emerging atypical porcine pestivirus (APPV), which is prevalent in swine herds and a serious threat to the pig production industry. This study aimed to construct APPV E2 subunit vaccines fused with Fc fragments and evaluate their immunogenicity in piglets. Here, APPV E2Fc and E2ΔFc fusion proteins expressed in Drosophila Schneider 2 (S2) cells were demonstrated to form stable dimers in SDS-PAGE and western blotting assays. Functional analysis revealed that aE2Fc and aE2ΔFc fusion proteins could bind to FcγRI on antigen-presenting cells (APCs), with the affinity of aE2Fc to FcγRI being higher than that of aE2ΔFc. Moreover, subunit vaccines based on aE2, aE2Fc, and aE2ΔFc fusion proteins were prepared, and their immunogenicity was evaluated in piglets. The results showed that the Fc fusion proteins emulsified with the ISA 201VG adjuvant elicited stronger humoral and cellular immune responses than the IMS 1313VG adjuvant. These findings suggest that APPV E2 subunit vaccines fused with Fc fragments may be a promising vaccine candidate against APPV.

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A randomized phase II trial of sipuleucel-T with concurrent or sequential abiraterone acetate (AA) plus prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5047 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5047-5047 ◽

Cited By ~ 3

Author(s):

Eric Jay Small ◽

Raymond S. Lance ◽

Charles H. Redfern ◽

Frederick E. Millard ◽

Thomas A. Gardner ◽

...

Keyword(s):

Immune Responses ◽

Similar Efficacy ◽

Abiraterone Acetate ◽

Cellular Immune Responses ◽

Randomized Phase Ii ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant ◽

Cellular Immune ◽

Antigen Presenting ◽

Clinical Trial Information

5047^ Background: Sipuleucel-T and AA + P are FDA-approved for asymptomatic/minimally symptomatic mCRPC. Suppression of the androgen axis can be immunostimulatory and AA suppresses circulating androgen levels; AA plus sipuleucel-T may therefore be synergistic. However P used with AA, which may be immunosuppressive, has not been studied with concurrent sipuleucelET and could impair sipuleucel-T production and/or immunologic response. P11-3 (NCT01487863) is the 1st study to evaluate the combination of sipuleucel-T and AA + P Methods: Patients (pts) with asymptomatic/minimally symptomatic mCRPC were randomized (1:1) to sipuleucel-T (3 infusions at approx 2-wk intervals) with up to 26 wks of AA + P (AA 1000mg QD + P 5mg BID) starting 1 day after the 1st sipuleucel-T infusion (concurrent, arm A) or at 10 wks following the 1st sipuleucel-T infusion (sequential, arm B). Endpoints included the effect of AA + P on product (sipuleucel-T) characteristics eg antigen presenting cell (APC) activation, measured as CD54 upregulation (primary endpoint), APC (measured as CD54+ cells) and total nucleated cell (TNC) counts, as well as safety and immunologic responses. Results: 31 pts in arm A and 32 pts in arm B completed sipuleucel-T treatment by the interim analysis (Nov 2012). Baseline characteristics were similar in the 2 arms. 60/63 pts received all 3 infusions of sipuleucel-T. No significant differences in median cumulative APC activation, APC count or TNC count were seen between the arms. Increased CD54 upregulation with the 2nd and 3rd treatments were indicative of a prime boost effect in both arms. Similar profiles of antigen-specific humoral and cellular immune responses were generated with no difference in magnitude of response between the arms (p>0.05). The incidence of adverse events (AEs) and serious AEs was similar in both arms. Conclusions: These data suggest sipuleucel-T can be successfully manufactured during concurrent AA + P. Product potency and prime boost effect were similar to sipuleucel-T alone. Immune responses and AEs were similar in both arms. It is not known if sipuleucel-T will provide similar efficacy with concurrent or sequential AA + P. Clinical trial information: NCT01487863.

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Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice

PLoS ONE ◽

10.1371/journal.pone.0150678 ◽

2016 ◽

Vol 11 (3) ◽

pp. e0150678 ◽

Cited By ~ 12

Author(s):

Li Song ◽

Dan Xiong ◽

Maozhi Hu ◽

Xilong Kang ◽

Zhiming Pan ◽

...

Keyword(s):

Immune Responses ◽

Subunit Vaccines ◽

Cellular Immune Responses ◽

H7n9 Influenza ◽

Cellular Immune

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Oral Salmonella typhimurium vaccine expressing circumsporozoite protein protects against malaria

Science ◽

10.1126/science.3281260 ◽

1988 ◽

Vol 240 (4850) ◽

pp. 336-338 ◽

Cited By ~ 168

Author(s):

JC Sadoff ◽

WR Ballou ◽

LS Baron ◽

WR Majarian ◽

RN Brey ◽

...

Keyword(s):

Immune Responses ◽

Salmonella Typhimurium ◽

Plasmodium Berghei ◽

Protein A ◽

Cell Mediated Immunity ◽

Specific Cell ◽

T Cell Epitopes ◽

Subunit Vaccines ◽

Cellular Immune Responses ◽

Cellular Immune

Immunization with radiation-attenuated malaria sporozoites induces potent cellular immune responses, but the target antigens are unknown and have not previously been elicited by subunit vaccines prepared from the circumsporozoite (CS) protein. A method is described here for inducing protective cell-mediated immunity to sporozoites by immunization with attenuated Salmonella typhimurium transformed with the Plasmodium berghei CS gene. These transformants constitutively express CS antigens and, when used to immunize mice orally, colonize the liver, induce antigen-specific cell-mediated immunity, and protect mice against sporozoite challenge in the absence of antisporozoite antibodies. These data indicate that the CS protein contains T cell epitopes capable of inducing protective cell-mediated immunity, and emphasize the importance of proper antigen presentation in generating this response. Analogous, orally administered vaccines against human malaria might be feasible.

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Hexahistidine–Metal Assemblies: A Facile and Effective Codelivery System of Subunit Vaccines for Potent Humoral and Cellular Immune Responses

Molecular Pharmaceutics ◽

10.1021/acs.molpharmaceut.0c00212 ◽

2020 ◽

Vol 17 (7) ◽

pp. 2487-2498 ◽

Cited By ~ 1

Author(s):

Tinghong Zhang ◽

Long Zhang ◽

Xiaoxiao Wu ◽

Hongyan Xu ◽

Pengyan Hao ◽

...

Keyword(s):

Immune Responses ◽

Subunit Vaccines ◽

Cellular Immune Responses ◽

Cellular Immune

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Differentiation, Maturation, and Survival of Dendritic Cells by Osteopontin Regulation

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.1.206-212.2005 ◽

2005 ◽

Vol 12 (1) ◽

pp. 206-212 ◽

Cited By ~ 50

Author(s):

Kodai Kawamura ◽

Kazuhiro Iyonaga ◽

Hidenori Ichiyasu ◽

Junji Nagano ◽

Moritaka Suga ◽

...

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Human Monocyte ◽

Matrix Component ◽

Cellular Immune Responses ◽

Histocompatibility Complex ◽

Important Interaction ◽

Cellular Immune ◽

Antigen Presenting ◽

Class Ii Antigens

ABSTRACT Dendritic cells (DCs) are antigen-presenting cells with the ability to induce primary immune responses necessary in innate immunity and adaptive immunity. Osteopontin (OPN) is a secreted acidic phosphoprotein containing an arginine-glycine-aspartate sequence and has been suggested to play an important role in early cellular immune responses. The interaction between DCs and OPN has not been clarified. We hypothesized that there is an important interaction between DCs and OPN, which is an indispensable extracellular matrix component in early cellular immune responses. Human monocyte-derived DCs synthesized OPN especially during the differentiation from monocytes to immature DCs. By blocking of OPN with anti-OPN antibody, cultured DCs became smaller and expressed lower levels of costimulatory molecules and major histocompatibility complex class II antigens than untreated DCs. Furthermore, DCs treated with anti-OPN antibody easily underwent apoptosis. These results suggest that human DCs can produce OPN and that OPN may play a role in the differentiation, maturation, and survival of DCs by autocrine and/or paracrine pathways.

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