The imbalance of the Th17/Treg axis following equine ascending placental infection.

ABSTRACT The development of safe and efficient vaccines against coronavirus disease 2019 (COVID-19) is necessary for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 vaccines. Among the available vaccine types, DNA vaccines are a promising alternative to conventional vaccines. Here, we developed a novel DNA vaccine containing the SARS-CoV-2 S1 subunit and an optimized flagellin adjuvant (FliCΔD2D3) from Salmonella typhimurium. The S1 gene and S1-fliCΔD2D3 fusion gene were codon optimized and then cloned into the antibiotic-resistance-gene-free vector asd-pVAX1, producing asd-pVAX1-S1 and asd-pVAX1-S1-fliCΔD2D3, respectively. The expression of S1 and S1-FliCΔD2D3 proteins was confirmed after transient expression in HEK293T cells. After in vitro characterization of the vaccine candidates, we evaluated the humoral and cellular immune responses induced in BALB/c mice. The DNA vaccine induced a long-lasting humoral response for approximately 4 months, and the elicited serum antibodies efficiently blocked the binding of the SARS-CoV-2 S1 receptor-binding domain to its entry receptor (angiotensin-converting enzyme 2). Moreover, the DNA vaccine induced strong Th1/Th2-mixed immune responses, as demonstrated by the similar levels of S1-specific immunoglobulin (Ig) G1 and IgG2a in the serum and the significantly elevated Th1-type (IFN-γ and TNF-α) and Th2-type (IL-4 and IL-6) cytokine expression from splenic lymphocytes. Importantly, asd-pVAX1-S1-fliCΔD2D3 immunization in mice could significantly enhance the levels of immune responses compared to asd-pVAX1-S1. This study provides crucial information regarding the selection of a safer DNA vector and a new adjuvant for the vaccine development of SARS-CoV-2 and other infectious diseases. IMPORTANCE The development of safe and effective vaccines is needed to control the transmission of coronavirus disease 2019 (COVID-19). Synthetic DNA vaccines represent a promising platform in response to such outbreaks. Here, DNA vaccine candidates were developed using an optimized antibiotic-resistance gene-free asd-pVAX1 vector. An optimized flagellin (FliC) adjuvant was designed by fusion expression to increase the immunogenicity of the S1 antigen. S1 and S1-FliCΔD2D3 proteins were strongly expressed in mammalian cells. The FliCΔD2D3-adjuvanted DNA vaccine induced Th1/Th2-mixed immune responses and high titers of neutralizing antibodies. This study provides crucial information regarding the selection of a safer DNA vector and adjuvant for vaccine development. Our FliCΔD2D3-adjuvanted S1 DNA vaccine is more potent at inducing both humoral and cellular immune responses than S1 alone. This finding provides a new idea for the development of novel DNA vaccines against COVID-19 and could be further applied for the development of other vaccines. The development of safe and effective vaccines is needed to control the transmission of coronavirus disease 2019 (COVID-19). Synthetic DNA vaccines represent a promising platform in response to such outbreaks. Here, DNA vaccine candidates were developed using an optimized antibiotic-resistance gene-free asd-pVAX1 vector. An optimized flagellin (FliC) adjuvant was designed by fusion expression to increase the immunogenicity of the S1 antigen. S1 and S1-FliCΔD2D3 proteins were strongly expressed in mammalian cells. The FliCΔD2D3-adjuvanted DNA vaccine induced Th1/Th2-mixed immune responses and high titers of neutralizing antibodies. This study provides crucial information regarding the selection of a safer DNA vector and adjuvant for vaccine development. Our FliCΔD2D3-adjuvanted S1 DNA vaccine is more potent at inducing both humoral and cellular immune responses than S1 alone. This finding provides a new idea for the development of novel DNA vaccines against COVID-19 and could be further applied for the development of other vaccines.

Enhanced immunogenicity elicited by a novel DNA vaccine encoding the SARS-CoV-2 S1 protein fused to the optimized flagellin of Salmonella typhimurium in mice

The Equine Strangles, caused by Streptococcus equi subs. equi, is a contagious disease, causing high rates of morbidity been responsible for important economic losses. The M protein synthesized by S. equi plays an important role in the pathogenesis and is a promising candidate for a vaccine antigen. The innate immune system is responsible for the first immune response against microorganisms, this response is mediated by receptors that detect PAMPs and their activation trigger crucial modulation of the adaptative immune response. This work describes the immune response of S. equi subs. equi. recombinant SeM protein, using Escherichia coli BL21 (DE3) as an expression and delivery vaccine system. To characterize and to determine the vaccine efficacy, mice were vaccinated as followed: 1. Recombinant E. coli expressing rSeM protein; 2. The same recombinant E. coli, inactivated adsorbed in Alumen; 3. Purified rSeM protein adsorbed in Alumen; 4. Inactivated S. equi whole cells adsorbed in Alumen; 5. Control group. All vaccinated mice developed protective response against S. equi infection, however the groups that received the E. coli expressing rSeM presented significant higher IgG level than other vaccinated groups. The recombinant E. coli delivery vaccine system also induced a highest IgG response than inactivated S. equi or purified rSeM vaccines in horses. This study evidence that the recombinant E. coli, live or inactivated, enhanced the humoral response, reaching significant higher antibodies levels than those obtained in the vaccination with the bacterin or purified antigen, showing the feasibility of producing lowcost vaccines against strangles.

Immunogenicity of Escherichia Coli Expressing Streptococcus Equi Subsp. Equi Recombinant SeM

Antibody kinetics and immune profile analysis of a Streptococcus equi DNA vaccine expressing the FljB and SeM fusion protein in murine and equine models

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Antibody kinetics and immune profile analysis of a Streptococcus equi DNA vaccine expressing the FljB and SeM fusion protein in murine and equine models