Immunologists at Zoetis were confident that a porcine circovirus type 2 (PCV2) vaccine with two circulating genotypes — PCV2a and 2b — would provide a broad range of coverage against PCV2 viruses in US and Canadian swine herds.
How much coverage was purely speculative, however. To see if they were on the right track, they collaborated with EpiVax, an informatics and immunology biotechnology company, that develops computational immunology tools.
An epitope is part of an antigen that is recognized by the immune system, specifically by immune cells — including lymphocytes known as T cells. T cells are essential for the development of an effective antibody response. Using a process called EpiCC to analyze T cell epitopes, EpiVax and Zoetis scientists could predict immune response and plot the coverage of different vaccines against PCV2a, 2b and 2d, the most prevalent genotypes affecting US and Canadian herds, as well as genotypes 2c, 2e and 2f, which are rare or absent in the US and Canada.1
EVOLVING FIELD STRAINS
“Through this computer model, we determined that putting PCV2a and PCV2b in one vaccine could provide considerably more coverage against the evolving field strains of the virus than traditional PCV2 vaccines with only one genotype,” explained Meggan Bandrick, DVM, PhD, senior manager, global biologics research, Zoetis.2
“With this technology, we could predict what the pig’s immune system would identify and how that might influence vaccine performance against various strains of the virus.”
To make this work, Zoetis obtained sequences for 161 field strains of PCV2 from GenBank, a voluntary repository of global sequences, and provided them to EpiVax for the analysis.
The strains were selected to broadly represent the different PCV2 types found globally. “We looked at 161 strains because there’s a lot of diversity in PCV2 and it continues to evolve,” Bandrick added.
EpiVax used the EpiCC computational method to predict how swine T cells recognize and bind T cell epitopes — in this case, about 800,000 different ones — and develop an immune response to either a pathogen or vaccine antigen.
“EpiCC takes the antigen-binding regions of swine T cells, predicted from the swine-genome sequence, and compares that to the same predicted binding regions or complementary regions on vaccine strains and on field strains,” Bandrick explained.
“Based on this, we can determine how the vaccine is going to convey information to the pig’s immune system so that the vaccine confers protection not only to the vaccine strain but also to field strains.”
PCV2 vaccine antigens or antigen combinations from three commercial vaccines were used in the analysis: Fostera Gold PCV MH (PCV2a plus PCV2b); Fostera PCV MH (PCV2a only); and a vaccine made with a baculovirus-derived PCV2a antigen. All are used in combination with Mycoplasma hyopneumoniae.
A radar plot (Figure 1) shows the results. The field strains are grouped together by genotype and identified on the perimeter. Each of the 161 PCV2 field strains in the analysis is represented by a single line running from the perimeter to the center. The three jagged starburst patterns inside the radar plot represent each vaccine’s T cell epitopes compared to that specific field strain in the analysis.
“Note that the amount of T cell epitope overlap indicating immune coverage increases going from the center of the circle to the perimeter,” Bandrick said, pointing to the chart. “The bigger the circle, the greater the coverage of the vaccine.”
The orange line representing Fostera Gold PCV MH covers a considerably broader range than either the gray (baculovirus-derived PCV2a) or the blue (Fostera PCV MH) lines, she added.
“In the vast majority of the cases, we found a significant improvement in coverage from having both PCV2a and PCV2b in the vaccine compared to just having 2a,” reported Dennis L. Foss, DVM, PhD, research director, Zoetis. “The 2b and 2d viruses are more closely related to each other than to the 2a viruses. Targeting the b-d clusters with a PCV2b vaccine makes sense and is supported by the EpiCC analysis.”
The scientists cautioned that the vaccine coverage shown in a computer model predicts rather than proves protection. That would have to be demonstrated by conducting multiple studies challenging pigs with different strains.
“Nonetheless, we would expect a strong correlation between pig response to these field-circulating strains and the coverage of the vaccine used,” Bandrick added. “The broader coverage of Fostera Gold PCV MH is important — not just for swine herds today, but also as the PCV2 virus continues to evolve.”
- Personal communication between André Broes, DVM, Biovet, and Josée Daigneault, DVM, Zoetis.
- Bandrick MM, Foss DL, Desai P, et al. EpiCC analysis of T cell epitope overlap among PCV2 vaccine and field strains. Poster I-250. 25th International Pig Veterinary Society Congress (IPVSC). 2018 International PRRS Symposium.
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