Electroporation enhances immune responses and protection induced by a bovine viral diarrhea virus DNA vaccine in newborn calves with maternal antibodies

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 ◽  
...  
2021 ◽  
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.


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.


2018 ◽  
Vol 44 (1) ◽  
pp. 6 ◽  
Author(s):  
Camila Costa Baccili ◽  
Natália Meirelles Sobreira ◽  
Bruno Toledo Silva ◽  
Edviges Maristela Pituco ◽  
Viviane Gomes

Background: Newborn calves are agammaglobulinemic, immunosuppressed and immunologically immature at birth. The passive immune transfer is fundamental to protect calves against pathogens. The decay of maternal antibodies precedes the immune maturation at puberty enhancing the susceptibility of calves to infections caused by BVDV. Then, the objective of this research was to evaluate the interface between passive and active immunity for Bovine Viral Diarrhea Virus (BVDV) in Holstein dairy heifers in the first 13 months of age to detect susceptibility periods and establish prophylactic measures on prevention of Bovine Viral Diarrhea.Materials, Methods & Results: Sera were analyzed from 585 heifers by serum neutralization (SN) and enzyme linked immunosorbent assay (ELISA) for the p80 protein of BVDV. Heifers were categorized according to their age by the month of life. Heifers were seropositive (100%) from 1st to 13th. Median of neutralizing antibodies (Ab) titers obtained from 1st up to 13th month were 316.2; 125.9; 63.1; 50.1; 50.1; 39.8; 63.1; 63.1; 39.8; 79.4, 100.0; 74.4; and 79.4, respectively. The neutralizing Ab titers obtained in 1st month were different of the values observed from 2nd until 13th (P < 0.001), furthermore the Ab titers from 2nd month was statistical different of 4th (P = 0.01) and 6th (P = 0.05). The frequencies (%) of positive heifers for p80 from 1st up to 13th were 24.7; 18.2; 10.4; 11.8; 73.3; 73.8; 72.4; 58.1; 45.9; 48.4; 46.2; 43.8 and 61.5, respectively. The correlation observed for neutralizing Ab titers and age was negative and weak (ρ= -0.299; P < 0.001). On the other hand, the correlation between positive heifers for p80 and age was positive and moderate (ρ= 0.319; P < 0.001).Discussion: The newborn calves had higher titers of neutralizing antibodies than other age groups and some calves were seropositive for the p80 protein. This profile points to the transfer of maternal antibodies produced by vaccination and/or natural exposure to BVDV. The exposure of the cows to the inactivated and live virus stimulates the production of neutralizing antibodies to the structural proteins of the virus, particularly the glycoprotein E2, detected by the serum neutralization test. The titers of serum neutralizing antibodies and the frequencies of seropositive for p80 protein decreased gradually from the first to the 4-6th month of life due to the metabolization of maternal immunoglobulins acquired by ingestion of colostrum. Frequencies of seropositive animals for protein p80 increased from the fifth month of life, which is the same moment that was observed declined of neutralizing maternal antibody titers. The phase of higher frequency of p80 positive animals coincides with greater rates of Babesiosis and Anaplasmosis. This history could justify the importance of the BVDV immunodepression as a risk factor for concomitant diseases. In general, the neutralizing antibody titers increased after the peaks of positive reactions to the p80 protein, but this moment coincides with the primo-vaccination in calves. Therefore, it is not possible to state the origin of these antibodies. Correlations between ages and serologic tests are consistent with previous data reporting the decrease in antibody titers and increase of seropositive animals for p80 protein, from the first month of life to puberty. In conclusion, maternal neutralizing Ab titers had gradual decreased whereas the frequency of positive heifers for p80 had increased values. The inversion observed between the maternal antibody titers and the increase in antibody for p80 indicates the moment of greatest risk for natural infections caused by 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.


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