Linking phenotype to genotype: a study of antibody responses to bovine respiratory virus vaccines in a crossbred cattle population

O'Neill, Ronan G. (2006) Linking phenotype to genotype: a study of antibody responses to bovine respiratory virus vaccines in a crossbred cattle population. PhD thesis, University of Glasgow.

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Vaccination is central to prevention of infectious disease in modern livestock production systems. Accurate assessment of the many factors controlling immune responses to vaccination is crucial to maximising their effectiveness. Identification of the genetic component of those immune responses is a prelude to selection for disease resistance. Assignment of those effects at a molecular level should lead to a more complete understanding of the complex processes underlying immunity. The overall aim of this study was to evaluate the IgG antibody responses induced by vaccination in a juvenile, fully pedigreed bovine population of Holstein-Charolais crossbred animals. Vaccines against bovine respiratory syncytial virus (BRSV), bovine parainfluenza 3 virus (PIV3) and bovine herpesvirus 1 (BHVl) were administered to 463 calves, aged 60 to 167 days old. Antibody responses to field infections against bovine coronavirus (BCV) were also examined. The experimental population comprised second-cross Holstein-Charolais F2, Holstein-backcross and Charolais-backcross animals with a daily-type calf-rearing scheme employed for females and a beef-type calf-rearing method for males. All datasets were extensively investigated using Residual Maximum Likelihood (REML) procedures. Across the population, there was a broad spectrum of antibody responses to vaccination. Mean antibody half-lifes were estimated as -24 days for total BRSV-IgG, -72 days for BRSV-IgG2, -32 days for total PIV3 IgG and -26 days for total BHVl-IgG. Although PIV3 and BHVl are both components of a multivalent intranasal vaccine, the BHVl-IgG response was poor while the PIV3-IgG response was substantial. Sex, year-of-birth, cross-breeding, animal age, and levels of pre existing antibody were significant sources of variation for levels of IgG antibodies against all viruses in this population. Although the effect is confounded by management, female calves had higher levels of BRSV-IgG and PIV3-IgG. Despite year-of-birth effect, including seasonality in climate, environment, wild-type infections and management, it accounted for a lower order of the observed variation than sex. Pre-vaccination, calves from dams with higher percentages of the Holstein breed had higher levels of BRSV-IgG and PIV3-IgG. Dam-age was also positively correlated with pre-vaccination levels of BRSV-IgG, the effect plateauing at about 4 years old. Although calf-age was a significant pre-vaccination determinant, its effect on post-vaccination levels of IgG was much less pronounced. The inhibitory effect of pre-existing BRSV-IgG and PIV3-IgG on vaccine response was analysed using logistic regression and respective relative optical density thresholds of -26% and -35% established. Pre-vaccination IgG above these levels meant a positive antibody response was less likely than a negative one. Pre-vaccination, maternal heritable effects dominated total phenotypic variance but postvaccination, additive heritable effects became more important. Estimates of heritability (+/-se) peaked at 0.29 (+/-0.17) for total BRSV-IgG (Day 35); 0.52 (+/-0.26) for the deviation in BRSV-IgG levels between Day 0 and Day 35; 0.47 (+/-0.28; Day 28) and 0.51 (+/-0.31; Day 42) for total PIV3-IgG in the male and female calves, respectively. Much lower values were recorded for BHVl and BCV IgG responses. All calves underwent genotyping and were mapped for 139 microsatellite markers with an average marker interval of 15. centiMorgans (cM). Interval analysis for quantitative trait loci (QTL) using the above antibody phenotypes revealed a large number of loci (positions in cM) influencing levels of IgG. Quantitative trait loci on BTAl (59 cM), BTA2 (108 cM), BTA7 (29 cM), BTA8 (41 cM), BTAIO (55 cM), BTAl2 (84 cM), BTA24 (44 cM) and BTA28 (2 cM) proved significant for one or more of the BRSV-, PIV3- and BHVl-IgG antibody traits. Although the QTL for antibody phenotype identified here are preliminary, they could plausibly be incorporated into breeding programmes to influence antibody response to vaccination. Further, they could act as a basis for further QTL research in this area leading to precise isolation of the relevant genes involved, to a molecular level. However most of all, these results prove that antibody production in cattle is under quantitative genetic control and this influential element should not be disregarded in the future.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Animal diseases, cattle, viral vaccines.
Subjects: Q Science > QR Microbiology > QR180 Immunology
S Agriculture > SF Animal culture > SF600 Veterinary Medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Supervisor's Name: Fitzpatrick, Prof. Julie and Glass, Dr. Liz
Date of Award: 2006
Depositing User: Enlighten Team
Unique ID: glathesis:2006-71912
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 09:31
Last Modified: 20 May 2021 19:56

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