The HSP70-fused foot-and-mouth disease epitope elicits cellular and humoral immunity and drives broad-spectrum protective efficacy

Jo, Hyundong; Kim, Bong Yoon; Park, So Hui; Kim, Hyun Mi; Shin, Sung Ho; Hwang, Seong Yun; Kim, Su-Mi; Kim, Byounghan; Lee, Min Ja

doi:10.1038/s41541-021-00304-9

Cited by 17 publications

(49 citation statements)

References 38 publications

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“…The animal protocol was conducted according to the method described by Lee et al and Jo et al 17 , 67 . Age- and sex-matched wild-type C57BL/6 mice (females, 6–7 weeks old) were purchased from KOSA BIO Inc. (Gyeonggi, Korea).…”

Section: Methodsmentioning

confidence: 99%

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The C3d-fused foot-and-mouth disease vaccine platform overcomes maternally-derived antibody interference by inducing a potent adaptive immunity

et al. 2022

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Vaccination prevents and controls foot-and-mouth disease (FMD). However, the current FMD vaccine remains disadvantageous since it cannot overcome maternally-derived antibody (MDA) interference in weeks-old animals, which suppress active immunity via vaccination. To address this, we developed the immune-enhancing O PA2-C3d and A22-C3d FMD vaccine strains that can stimulate receptors on the surface of B cells by inserting C3d (a B cell epitope) into the VP1 region of O PA2 (FMDV type O) and A22 (FMDV type A). We purified inactivated viral antigens from these vaccine strains and evaluated their immunogenicity and host defense against FMDV infection in mice. We also verified its efficacy in inducing an adaptive immune response and overcome MDA interference in MDA-positive (MDA(+), FMD-seropositive) and -negative (MDA(−), FMD-seronegative) pigs. These results suggest a key strategy for establishing novel FMD vaccine platform to overcome MDA interference and induce a robust adaptive immune response.

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Section: Methodsmentioning

confidence: 99%

“…Porcine PBMCs were isolated from whole blood of FMD antibody-seronegative pigs as donors (8-9 weeks old animals, n = 3/group) according to the method described by Lee et al and Jo et al 17 , 67 . Whole blood (20 mL/donor) was independently collected in BD Vacutainer heparin tubes (BD, Becton, Dickinson and Company, Franklin Lakes, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

The C3d-fused foot-and-mouth disease vaccine platform overcomes maternally-derived antibody interference by inducing a potent adaptive immunity

et al. 2022

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“…A VNT was performed based on the guidelines set forth by the World Organization for Animal Health (OIE) manual [ 24 ], as described by Lee et al and Swaney [ 25 , 26 , 27 , 28 ]. Briefly, sera were heat-inactivated at 56 °C for 30 min in a water bath.…”

Section: Methodsmentioning

confidence: 99%

“…ELISAs for porcine IL-2, IL-10, and TGFβ (Cloud-Clone Corporation, Houston, TX, USA) in serum were performed according to the manufacturer’s instructions. The subsequent steps were as described for antibody isotype-specific immunoassays [ 25 , 26 , 27 ].…”

Section: Methodsmentioning

confidence: 99%

Age-Dependent Dynamics of Maternally Derived Antibodies (MDAs) and Understanding MDA-Mediated Immune Tolerance in Foot-and-Mouth Disease-Vaccinated Pigs

Shin

Park

et al. 2022

Vaccines

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Vaccine-induced active immunity in young animals may be compromised via interference caused by maternally derived antibodies (MDAs). Since the level, titer, and half-life of MDAs vary per individual, it is difficult to determine the appropriate timing of foot-and-mouth disease (FMD) vaccination in the field. In order to better understand the age-dependent characteristics of MDA in sows and piglets as well as the phenomenon of reduced vaccine-mediated active immunity due to MDAs, this study sought to determine antibody titers through structural protein (SP) O, A ELISA analyses, and virus-neutralizing (VN) antibody titers as well as their half-lives in the sera of sows and piglets derived from FMD-vaccinated mother. Furthermore, immunoglobulin (Ig) subtypes, such as IgG, IgM, and IgA, in serum were also evaluated. To understand the correlation between the inhibition of vaccine-mediated active immunity by MDA-mediated passive immunity and regulatory T (Treg) cells, Treg-related cytokine levels were explored. Our findings will help to predict the optimal timing of vaccination for overcoming MDAs and inducing a robust vaccine-mediated immune response in young individuals vaccinated against FMD. They also add to our understanding of MDA characteristics and interference, providing insight for the development of innovative strategies and novel FMD vaccine for overcoming such interference.

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“…Protein-based subunits vaccines are generally considered safe; however, they can be weakly immunogenic, often requiring the addition of adjuvants to elicit an effective immune response (Perez et al, 2012;Jo et al, 2021). Despite several adjuvants have been assayed in experimental subunit vaccines against T. gondii (Sander et al, 2018;Şahar et al, 2020), the search for safer and non-toxic adjuvants capable of strongly boosting and directing immune responses is still one of the main challenges in this field.…”

Section: Introductionmentioning

confidence: 99%

Oral Immunization With a Plant HSP90-SAG1 Fusion Protein Produced in Tobacco Elicits Strong Immune Responses and Reduces Cyst Number and Clinical Signs of Toxoplasmosis in Mice

et al. 2021

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Plant 90kDa heat shock protein (HSP90) is a potent adjuvant that increases both humoral and cellular immune responses to diverse proteins and peptides. In this study, we explored whether Arabidopsis thaliana HSP90 (AtHsp81.2) can improve the immune effects of a Toxoplasma gondii surface antigen 1 (SAG1). We designed two constructs containing the sequence of mature antigen (SAG1m), from aa77 to aa322, and B- and T-cell antigenic epitope-containing SAG1HC, from aa221 to aa319 fused to AtHsp81.2 sequence. When comparing the transient expression in Nicotiana tabacum X-27-8 leaves, which overexpress the suppressor helper component protease HC-Pro-tobacco etch virus (TEV), to that in N. benthamiana leaves, co-agroinfiltrated with the suppressor p19, optimal conditions included 6-week-old N. benthamiana plants, 7-day time to harvest, Agrobacterium tumefaciens cultures with an OD600nm of 0.6 for binary vectors and LED lights. While AtHsp81.2-SAG1m fusion protein was undetectable by Western blot in any of the evaluated conditions, AtHsp81.2–SAG1HC was expressed as intact fusion protein, yielding up to 90μg/g of fresh weight. Besides, the AtHsp81.2–SAG1HC mRNA was strongly expressed compared to the endogenous Nicotiana tabacum elongation factor-alpha (NtEFα) gene, whereas the AtHsp81.2–SAG1m mRNA was almost undetectable. Finally, mice were orally immunized with AtHsp81.2–SAG1HC-infiltrated fresh leaves (plAtHsp81.2–SAG1HC group), recombinant AtHsp81.2–SAG1HC purified from infiltrated leaves (rAtHsp81.2–SAG1HC group), non-infiltrated fresh leaves (control group), or phosphate-buffered saline (PBS group). Serum samples from plAtHsp81.2–SAG1HC-immunized mice had significantly higher levels of IgGt, IgG2a, and IgG2b anti-SAG1HC antibodies than serum from rAtHsp81.2–SAG1HC, control, and PBS groups. The number of cysts per brain in the plAtHsp81.2–SAG1HC-immunized mice was significantly reduced, and the parasite load in brain tissue was also lower in this group compared with the remaining groups. In an immunoblot assay, plant-expressed AtHsp81.2-SAG1HC was shown to react with antibodies present in sera from T. gondii-infected people. Therefore, the plant expression of a T. gondii antigen fused to the non-pathogenic adjuvant and carrier plant HSP90 as formulations against T. gondii can improve the vaccine efficacy, and plant extract can be directly used for vaccination without the need to purify the protein, making this platform a suitable and powerful biotechnological system for immunogenic antigen expression against toxoplasmosis.

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The HSP70-fused foot-and-mouth disease epitope elicits cellular and humoral immunity and drives broad-spectrum protective efficacy

Cited by 17 publications

References 38 publications

The C3d-fused foot-and-mouth disease vaccine platform overcomes maternally-derived antibody interference by inducing a potent adaptive immunity

The C3d-fused foot-and-mouth disease vaccine platform overcomes maternally-derived antibody interference by inducing a potent adaptive immunity

Age-Dependent Dynamics of Maternally Derived Antibodies (MDAs) and Understanding MDA-Mediated Immune Tolerance in Foot-and-Mouth Disease-Vaccinated Pigs

Oral Immunization With a Plant HSP90-SAG1 Fusion Protein Produced in Tobacco Elicits Strong Immune Responses and Reduces Cyst Number and Clinical Signs of Toxoplasmosis in Mice

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