{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:12:25Z","timestamp":1790626345324,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"USDA\/Agricultural Research Service, National Animal Disease Center","award":["5030-32000-229-00D"],"award-info":[{"award-number":["5030-32000-229-00D"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Bovine viral vaccines contain both live or inactivated\/killed formulations, but few studies have evaluated the impact of vaccinating with either live or killed antigens and re-vaccinating with the reciprocal. Commercial dairy heifers were utilized for the study and randomly assigned to three treatment groups. Treatment groups received a commercially available modified-live viral (MLV) vaccine containing BVDV and were revaccinated with a commercially available killed viral (KV) vaccine containing BVDV, another group received the same KV vaccine and was revaccinated with the same MLV vaccine, and yet another group served as negative controls and did not receive any viral vaccines. Heifers in KV\/MLV had higher virus neutralizing titers (VNT) at the end of the vaccination period than heifers in MLV\/KV and control groups. The frequency of IFN-\u03b3 mRNA positive CD4+, CD8+, and CD335+ populations, as well as increased mean fluorescent intensity of CD25+ cells was increased for the MLV\/KV heifers as compared to KV\/MLV and controls. The data from this study would suggest that differences in initial antigen presentation such as live versus killed could augment CMI and humoral responses and could be useful in determining vaccination programs for optimizing protective responses, which is critical for promoting lifetime immunity.<\/jats:p>","DOI":"10.3390\/v15030703","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T02:33:16Z","timestamp":1678329196000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Response to Bovine Viral Diarrhea Virus in Heifers Vaccinated with a Combination of Multivalent Modified Live and Inactivated Viral Vaccines"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9305-6307","authenticated-orcid":false,"given":"Shollie M.","family":"Falkenberg","sequence":"first","affiliation":[{"name":"Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA"},{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8250-4370","authenticated-orcid":false,"given":"Rohana P.","family":"Dassanayake","sequence":"additional","affiliation":[{"name":"Ruminant Diseases and Immunology Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Crawford","sequence":"additional","affiliation":[{"name":"Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Sarlo Davila","sequence":"additional","affiliation":[{"name":"Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Boggiatto","sequence":"additional","affiliation":[{"name":"Infectious Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, IA 50010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.cvfa.2003.11.001","article-title":"Evolution of bovine viral diarrhea virus vaccines","volume":"20","author":"Kelling","year":"2004","journal-title":"Vet. Clin. Food Anim. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.cvfa.2016.01.011","article-title":"Diagnosis and control of viral diseases of reproductive importance: Infectious bovine rhinotracheitis and bovine viral diarrhea","volume":"32","author":"Newcomer","year":"2016","journal-title":"Vet. Clin. Food Anim. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.theriogenology.2014.09.028","article-title":"Efficacy of bovine viral diarrhea virus vaccination to prevent reproductive disease: A meta-analysis","volume":"83","author":"Newcomer","year":"2015","journal-title":"Theriogenology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1136\/vr.137.3.58","article-title":"Protection of the bovine fetus from bovine viral diarrhoea virus by means of a new inactivated vaccine","volume":"137","author":"Brownlie","year":"1995","journal-title":"Vet. Rec."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.vetmic.2017.03.016","article-title":"Bovine herpesvirus 1 modified live virus vaccines for cattle reproduction: Balancing protection with undesired effects","volume":"206","author":"Chase","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.vaccine.2017.01.006","article-title":"Evaluation of reproductive protection against bovine viral diarrhea virus and bovine herpesvirus-1 afforded by annual revaccination with modified-live viral or combination modified-live\/killed viral vaccines after primary vaccination with modified-live viral vaccine","volume":"35","author":"Walz","year":"2017","journal-title":"Vaccine"},{"key":"ref_7","first-page":"44","article-title":"Comparison of the BVDV, BHV-1, and BRSV anamnestic response to modified-live or inactivated vaccines in calves previously vaccinated with a modified-live virus vaccine","volume":"43","author":"Royan","year":"2009","journal-title":"Bov. Pract."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1046\/j.1439-0450.2002.00599.x","article-title":"Foetal protection against bovine virus diarrhoea virus after two-step vaccination","volume":"49","author":"Frey","year":"2002","journal-title":"J. Vet. Med. Ser. B"},{"key":"ref_9","first-page":"49","article-title":"Response to modified live and killed multivalent viral vaccine in regularly vaccinated, fresh dairy cows","volume":"1","author":"Dubovi","year":"2000","journal-title":"Vet. Ther. Res. Appl. Vet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Moennig, V., and Becher, P. (2018). Control of bovine viral diarrhea. Pathogens, 7.","DOI":"10.3390\/pathogens7010029"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.prevetmed.2005.08.011","article-title":"Implementation of two-step vaccination in the control of bovine viral diarrhoea (BVD)","volume":"72","author":"Moennig","year":"2005","journal-title":"Prev. Vet. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.rvsc.2020.01.012","article-title":"Comparative humoral immune response against cytopathic or non-cytopathic bovine viral diarrhea virus infection","volume":"129","author":"Rajput","year":"2020","journal-title":"Res. Vet. Sci."},{"key":"ref_13","first-page":"E1","article-title":"The induction of a cell-mediated immune response to bovine viral diarrhea virus with an adjuvanted inactivated vaccine","volume":"10","author":"Stevens","year":"2009","journal-title":"Vet. Ther. Res. Appl. Vet. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1016\/j.vaccine.2009.05.012","article-title":"Comparison of humoral and cellular immune responses to a pentavalent modified live virus vaccine in three age groups of calves with maternal antibodies, before and after BVDV type 2 challenge","volume":"27","author":"Platt","year":"2009","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.vetimm.2017.03.003","article-title":"Comparison of humoral and T-cell-mediated immune responses to a single dose of Bovela\u00ae live double deleted BVDV vaccine or to a field BVDV strain","volume":"187","author":"Platt","year":"2017","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.vetimm.2007.11.009","article-title":"Humoral and T cell-mediated immune responses to bivalent killed bovine viral diarrhea virus vaccine in beef cattle","volume":"122","author":"Platt","year":"2008","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"110024","DOI":"10.1016\/j.vetimm.2020.110024","article-title":"Measuring CMI responses using the PrimeFlow RNA assay: A new method of evaluating BVDV vaccination response in cattle","volume":"221","author":"Falkenberg","year":"2020","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"642","DOI":"10.3389\/fvets.2021.685114","article-title":"Evaluation of Antigenic Comparisons Among BVDV Isolates as it Relates to Humoral and Cell Mediated Responses","volume":"8","author":"Falkenberg","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5764","DOI":"10.1016\/j.vaccine.2020.07.010","article-title":"Multivariate analysis as a method to evaluate antigenic relationships between BVDV vaccine and field strains","volume":"38","author":"Mosena","year":"2020","journal-title":"Vaccine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1177\/1040638713518208","article-title":"Lack of evidence for the presence of emerging HoBi-like viruses in North American fetal bovine serum lots","volume":"26","author":"Bauermann","year":"2014","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/104063879100300302","article-title":"Methods for detection and frequency of contamination of fetal calf serum with bovine viral diarrhea virus and antibodies against bovine viral diarrhea virus","volume":"3","author":"Bolin","year":"1991","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"755","DOI":"10.2460\/ajvr.1995.56.06.755","article-title":"Assessment of protection from systemic infection or disease afforded by low to intermediate titers of passively acquired neutralizing antibody against bovine viral diarrhea virus in calves","volume":"56","author":"Bolin","year":"1995","journal-title":"Am. J. Vet. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0378-1135(00)00271-6","article-title":"Phylogenetic, antigenic and clinical characterization of type 2 BVDV from North America","volume":"77","author":"Ridpath","year":"2000","journal-title":"Vet. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1016\/j.vaccine.2018.04.005","article-title":"Comparison of reproductive protection against bovine viral diarrhea virus provided by multivalent viral vaccines containing inactivated fractions of bovine viral diarrhea virus 1 and 2","volume":"36","author":"Riddell","year":"2018","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1038\/s41564-020-0709-x","article-title":"The new scope of virus taxonomy: Partitioning the virosphere into 15 hierarchical ranks","volume":"5","author":"Gorbalenya","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.2460\/ajvr.79.11.1166","article-title":"Cell-mediated and humoral immune responses to bovine herpesvirus type 1 and bovine viral diarrhea virus in calves following administration of a killed-virus vaccine and bovine herpesvirus type 1 challenge","volume":"79","author":"Rinehart","year":"2018","journal-title":"Am. J. Vet. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.2460\/ajvr.67.7.1179","article-title":"Roth, Induction of antigen-specific T-cell subset activation to bovine respiratory disease viruses by a modified-live virus vaccine","volume":"67","author":"Platt","year":"2006","journal-title":"Am. J. Vet. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1099\/0022-1317-69-6-1399","article-title":"Influence of interferons \u03b111 and \u03b3 and of tumour necrosis factor on persistent infection with bovine viral diarrhoea virus in vitro","volume":"69","author":"Ohmann","year":"1988","journal-title":"J. Gen. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1093\/infdis\/jiaa664","article-title":"Differences in Influenza-Specific CD4 T-Cell Mediated Immunity Following Acute Infection Versus Inactivated Vaccination in Children","volume":"223","author":"Shannon","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1098\/rstb.1994.0149","article-title":"Infectious diseases, reproductive effort and the cost of reproduction in birds. Philosophical Transactions of the Royal Society of London","volume":"346","author":"Gustafsson","year":"1994","journal-title":"Ser. B Biol. Sci."},{"key":"ref_31","first-page":"340","article-title":"Mechanisms and methods in ecoimmunology: Integrating within-organism and between-organism processes","volume":"54","author":"Downs","year":"2014","journal-title":"Am. Zool."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1890\/04-1619","article-title":"Tree swallows trade off immune function and reproductive effort differently across their range","volume":"86","author":"Ardia","year":"2005","journal-title":"Ecology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1093\/icb\/icac033","article-title":"Timing of Breeding Reveals a Trade-Off between Immune Investment and Life History in Tree Swallows","volume":"62","author":"Oordt","year":"2022","journal-title":"Integr. Comp. Biol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/3\/703\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:50:53Z","timestamp":1760122253000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/3\/703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["v15030703"],"URL":"https:\/\/doi.org\/10.3390\/v15030703","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]}}}