scholarly journals Co-Administration of a Plasmid Encoding CD40 or CD63 Enhances the Immune Responses to a DNA Vaccine Against Bovine Viral Diarrhea Virus in a Mouse Model

Author(s):  
Leng Dongze ◽  
Shinji Yamada ◽  
Yusuke Chiba ◽  
Syuji Yoneyama ◽  
Yusuke Sakai ◽  
...  

Abstract Bovine viral diarrhea virus (BVDV) causes substantial economic losses in the livestock industry worldwide. Plasmids encoding the BVDV E2 protein are potential DNA vaccines against BVDV, but their immunogenicity has been insufficient. Here, we investigated the adjuvant effect of CD40 and CD63 on the immune responses to a BVDV E2 DNA vaccine in a mouse model. We constructed pUMVC4a-based plasmids encoding the BVDV E2 protein (pE2), mouse CD40 (pCD40), or mouse CD63 (pCD63). Protein expression by each plasmid was confirmed through Western blot analysis and immunofluorescence staining of cultured cell lines. BALB/c mice were immunized intradermally twice with pE2 in combination with, or without, pCD40 or pCD63, with 3 weeks between the two doses. pE2 with pCD40 induced significantly higher neutralizing antibody titers against BVDV than pE2 alone. Furthermore, pE2 with pCD40 or pCD63 induced significantly increased lymphocyte proliferation and IFN-γ production in response to BVDV ex vivo, compared with E2 alone. These results suggest that a plasmid encoding CD40 or CD63 can be used as an adjuvant to enhance immune responses to DNA vaccines against BVDV.

2006 ◽  
Vol 87 (10) ◽  
pp. 2971-2982 ◽  
Author(s):  
Rong Liang ◽  
Jan V. van den Hurk ◽  
Lorne A. Babiuk ◽  
Sylvia van Drunen Littel-van den Hurk

The objective of this study was to develop an optimal vaccination strategy for Bovine viral diarrhea virus (BVDV). The E2 protein of BVDV plays a major protective role against BVDV infection. In order to be able to compare DNA, protein and DNA prime–protein boost regimens, a plasmid was constructed encoding a secreted form of the NADL strain E2 protein (pMASIA-tPAsΔE2). Furthermore, a pure secreted recombinant ΔE2 (rΔE2) protein was produced. The rΔE2 protein was formulated with a combination of Emulsigen and CpG oligodeoxynucleotide. Groups of calves were immunized with pMASIA-tPAsΔE2 or with rΔE2, or first with pMASIA-tPAsΔE2 and then with rΔE2. To evaluate the protection against BVDV, calves were challenged with BVDV strain NY-1 after the last immunization. Although all immunized calves developed humoral and cellular immune responses, the antibody responses in the DNA prime–protein boost group were stronger than those elicited by either the DNA vaccine or the protein vaccine. In particular, E2-specific antibody titres were enhanced significantly after boosting the ΔE2 DNA-primed calves with rΔE2 protein. Moreover, protection against BVDV challenge was obtained in the calves treated with the DNA prime–protein boost vaccination regimen, as shown by a significant reduction in weight loss, viral excretion and lymphopenia, compared with the unvaccinated calves and the animals immunized with the DNA or protein only. These results demonstrate the advantage of a DNA prime–protein boost vaccination approach in an outbred species.


2012 ◽  
Vol 20 (2) ◽  
pp. 166-173 ◽  
Author(s):  
Sylvia van Drunen Littel-van den Hurk ◽  
Zoe Lawman ◽  
Marlene Snider ◽  
Don Wilson ◽  
Jan V. van den Hurk ◽  
...  

ABSTRACTBovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.


Vaccine ◽  
2010 ◽  
Vol 28 (39) ◽  
pp. 6445-6454 ◽  
Author(s):  
Sylvia van Drunen Littel-van den Hurk ◽  
Zoe Lawman ◽  
Don Wilson ◽  
Alain Luxembourg ◽  
Barry Ellefsen ◽  
...  

Vaccine ◽  
2014 ◽  
Vol 32 (50) ◽  
pp. 6758-6764 ◽  
Author(s):  
Marlene Snider ◽  
Ravendra Garg ◽  
Robert Brownlie ◽  
Jan V. van den Hurk ◽  
Sylvia van Drunen Littel-van den Hurk

2020 ◽  
Vol 7 ◽  
Author(s):  
María Eugenia Quintana ◽  
Lucas José Barone ◽  
Myrian Vanesa Trotta ◽  
Cecilia Turco ◽  
Florencia Celeste Mansilla ◽  
...  

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