Changes in circulating lymphocytes and lymphoid tissue associated with vaccination of colostrum deprived calves

Authors: Falkenberg, Shollie; Dassanayake, Rohana; Palmer, Mitchell; SILVERIA, SIMONE - Universidade Federal Do Rio Grande Do Norte; ROTH, JAMES - Iowa State University; GAUGER, ERIC - Boehringer Ingelheim; KAISER, TROY - Boehringer Ingelheim; GUIDARINI, CHRISTIAN - Boehringer Ingelheim; Neill, John; RIDPATH, JULIA - Retired ARS Employee

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/2020
Publication Date: 10/27/2020
Citation: Falkenberg, S.M., Dassanayake, R.P., Palmer, M.V., Silveria, S., Roth, J.A., Gauger, E., Kaiser, T., Guidarini, C., Neill, J.D., Ridpath, J. 2020. Changes in circulating lymphocytes and lymphoid tissue associated with vaccination of colostrum deprived calves. Vaccine. 38(46):7268-7277. https://doi.org/10.1016/j.vaccine.2020.09.046.
DOI: https://doi.org/10.1016/j.vaccine.2020.09.046

Interpretive Summary: The composition of currently available modified live viral (MLV) BVDV vaccines in the US, include cytopathic (cp) BVDV isolates and these vaccines may contain adjuvants. While currently available MLV vaccines contain cp vaccine strains, the strains used in each vaccine can differ. Given the difficulty of conferring fetal protection against BVDV, increased demand to develop vaccines that confer increased BVDV protection are desired. Different approaches have been employed to generate a strong immune response to BVDV, but it is unknown if these different approaches may cause negative immunological consequences. The goal of this study was to gain a better understanding of the outcomes associated with different BVDV vaccination approaches as it relates to depletion of immune parameters. Results from this study would suggest that different approaches that change the characteristics of the BVDV within the vaccines used in the current study can alter immunological measures. Data from this study highlight the importance and the need for BVDV antigens to be presented in multiple platforms to provide cattle producers with vaccine choices that can be tailored to the unique needs of each respective cattle operation.

Technical Abstract: The objective of this study was to compare immunological responses and lymphoid depletion in young, colostrum deprived (CD) calves following administration of vaccines containing modified-live bovine viral diarrhea virus (BVDV). Four vaccines included in the study contained cytopathic, (cp) conventional modified-live BVDV strains presented in combination with BoHV-1, BPI3V and BRSV (cp vaccines); one of these vaccines also included an adjuvant (adjuvanted cp vaccine). Two vaccines included in the study contained non-cytopathic (ncp) BVDV; one consisting of a conventional modified-live BVDV in combination with BoHV-1, BPI3V and BRSV (ncp vaccine), the other containing double-deleted, genetically modified (ddGM) BVDV type-1 and type 2 strains as a monovalent vaccine (ddGM vaccine). A group of calves exposed to a typical virulence ncp BVDV-2 field strain (ncp exposed) was included to compare responses of calves receiving vaccine to responses generated against a field strain (mimicking a natural infection). A negative control group administered a placebo was used in all comparisons. All vaccines used in the study were administered per manufacturer recommendations while ncp BVDV exposed calves received 5 ml intranasally (2.5 ml/nare; 4.2 times 106 TCID50/ml) of the BVDV-2 field strain. Samples collected at each time point included nasal swabs for virus detection, blood samples for complete blood counts and detection of viremia, PBMCs for flow cytometric analysis, serum for virus neutralization titers, and thymus tissue at necropsy for evaluation of lymphoid depletion. A measureable neutralizing BVDV titer was observed for all treatment groups excluding the control animals, which remained negative during the study period. Virus shedding was only detected from the ncp vaccine and ncp exposed calves. A decline from baseline was observed for peripheral lymphocyte and CD4plus cells for the groups receiving the adjuvanted cp vaccine, the ddGM vaccine, the ncp vaccine and ncp exposed calves, but not for the control group or groups receiving cp vaccines. Thymus depletion was observed for the ncp vaccine and ncp exposed calves and to a lesser extent for the ddGM vaccine calves. Collectively, these data suggest that the virus biotype, method of attenuation, presentation, and use of adjuvant will influence vaccine impacts on lymphoid tissues and the immune response. As such, multiple variables should be considered when determining costs and benefits of vaccination.