VACCINATION OF CATTLE IN LATE-TERM PREGNANCY FOR EPIZOOTIC BOVINE ABORTION: IS IT SAFE AND WILL IT CONFER LONG-TERM IMMUNITY TO THE RESULTING OFFSPRING?

• Sponsoring Institution: Cooperating Schools of Veterinary Medicine
• Project Status: COMPLETE
• Funding Source: STATE
• Reporting Frequency: Annual
• Accession No.: 1019397
• Project Start Date: Apr 10, 2019
• Project End Date: Sep 30, 2019
• Program Code: [(N/A)]- (N/A)

Recipient Organization
UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671

Performing Department
Pathology, Microbiology & Immunology

Non Technical Summary
In light of the infectious nature of the vaccine, USDA/CVB-approved Foothill Abortion Vaccination Trial protocol prohibits its' administration to any pregnant animal as a safety precaution, regardless of gestational age. The required 60-day window between vaccination and initiation of breeding to prevent early fetal loss has created hardship for many producers who wish to vaccinate aged cows (2nd calvers and older) but calve too late to provide the needed vaccination-to-breeding interval. Foothill abortion-associated losses in aged pregnant cows were especially severe in 2017-18 resulting in increased requests to vaccinate dams late in gestation resulting in initiation of this proposed research project which will hopefully expedite a resolution for these producers.

Animal Health Component

30%

Research Effort Categories

Basic

20%

Applied

30%

Developmental

50%

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
311	3310	1090	100%

Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3310 - Beef cattle, live animal;

Field Of Science
1090 - Immunology;

Keywords

epizootic bovine abortion

foothill abortion

vaccine

diagnostics

pajaroellobacter abortibovis

Goals / Objectives
A) Vaccinate naïve pregnant heifers at approximately 7 months gestation with the Pajaroellobacter abortibovis vaccine and determine any impact on fetal health (abortion or birth of weak calves), birth weights and calf weight gains.B) Establish the presence and persistence of P. abortibovis-specific antibodies in all resulting calves.C) Breed all female offspring (principals and controls) and challenge pregnant animals at approximately 100 days gestation with P. abortibovis to confirm immunity in those derived from late-term vaccinated dams.

Project Methods
Overall Design: Splenocytes will be recovered from SCID mice infected with P. abortibovis (Blanchard et al., 2010) and cryopreserved for use as vaccine using a protocol previously approved by USDA/CVB. Vaccine will be tested in accordance with USDA/CVB regulations to insure that potency (i.e. number of live-infected cells as determined by a combination of vital stain and flow cytometry; Brooks et al., 2016) exceeds 2,000 P.a. live infected cells (2,000 P.a.-LIC)/dose. Required sterility testing includes inoculation of two different media and incubation at two temperatures and safety studies include inoculation of vaccine into both mice and cattle. Bred heifers will be treated with either P. a. vaccine or placebo at 7-8 months gestation. All heifers will be tested for exposure to P. a. using serology prior to and following vaccination (P.a.-specific IFAT as previously described by Blanchard et al, 2014). Abortions or dying neonates will be subjected to diagnostics at the CA Animal Health & Food Safety Diagnostic Laboratory (CAHFS). Apparently healthy offspring will be followed for thriftiness as well as for the presence and persistence of P.a. antibodies. Female offspring of principals (controls and vaccinates) will be bred and challenged with live P. a. to demonstrate presence or absence of in utero-derived immunity.Obj A: Approximately fifty heifers will be synchronized and bred by AI with female sexed semen, rested for 2 weeks and bred by natural service for 1 cycle (i.e. 21 days) to maximize the number of female calves. Two ultrasound examinations will be conducted by UCD reproduction specialists to determine pregnancy and fetal sex. Presence of P. abortibovis-specific antibodies will be determined prior to vaccination; sero-positive animals will not be treated. Sero-negative heifers will be subdivided into those carrying male or female offspring and each group randomized into two treatment groups: vaccinates and placebo controls. Cattle will be treated at 7.5 months gestation ± 3 weeks gestation with either ~4000 P.a.-live-infected cells (LIC) or placebo (vaccine diluent), respectively. Aborted fetuses and dying neonates will be subjected to necropsy and diagnosis at CAHFS. All live calves in the herd will be weighed near the time of birth, branding and weaning as a measure of overall health and thriftiness.Obj B: All calves resulting from the pregnancies in Obj A will be bled at 1-2 months (i.e. at branding) and again at 6-7 months (i.e. weaning). A matching number of calves, born from cows within the larger UNR herd with P. abortibovis titers >800, will be bled and serve as controls for colostrum-derived P. a.-specific antibody.Obj C: All female offspring derived from Obj A will be maintained and bred as replacement heifers. These heifers will be bred at ~15 months of age and pregnant animals will be challenged with ~4000 P.a.-LIC at 90-110 days gestation. All aborted fetuses and weak neonates will be subjected to diagnostics at CAHFS.Data Analysis: Data analysis will employ one-way ANOVA. Regardless, a single fetal loss due to Foothill abortion from a vaccinated heifer will negate the future use of the vaccine in pregnant animals.

Progress 04/10/19 to 09/30/19

Outputs
Target Audience:Local and State (CA, OR & NV) Cattlemen's Associations, western beef producers, UC-Davis Center for Food Animal Health Stakeholder Workgroup Meeting, Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Artificial insemination & pregnancy evaluations using scanning technology was provided to senior food-animal veterinary students and theriogenology residents. Experience bleeding cows and calves was gained by undergraduates, DVM students and residents. How have the results been disseminated to communities of interest?UC-Davis Center for Food Animal Health Stakeholder Workgroup Meeting, California Cattlemen's Assocation Annual Animal Health Meeting What do you plan to do during the next reporting period to accomplish the goals?Determine if the heifers calves born to the naive dams that were infected with P. abortibovis in the 3rd trimester developed immunity in utero. These heifers will be raised to breeding age, bred, and then challenged with P. abortibovis at the peak time of fetal susceptibility (90-120 days gestation).

Impacts
What was accomplished under these goals? Data gathered to date on calf thriftiness from a 59 heifer study suggests that it is safe to vaccinate dams as they approach or exceed 7 months gestation. Calves exposed in utero to P. abortibovis have similar birth weights and show similar daily weight gainsto controls. Data suggests that vaccination is safest when administered >190 days gestation as one calf, whose dams was ~180 days gestation at the time of vaccination, was born weak and continues to do poorly with the lowest weight gains. This study underscores that extreme caution must be exercised by producers that choose to vaccinate naïve pregnant animals. While vaccination administered late in the 3rd trimester gestation appears safe, the number of naive dams vaccinated is small (16) and additional data is needed before implemented as a routine practice.

Publications

Progress 04/10/19 to 09/30/19

Outputs
Target Audience:Stakeholders (cow/calf producers, cattlemen's associations, extension Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Pregnancy evaluations were used for training purposes to instruct senior veterinary students and therio residents. Training in blood collection from young calves was also achieved. How have the results been disseminated to communities of interest?Preliminary results will be delivered to the industry at the California Cattlemen's Assocation Annual Meeting in December. What do you plan to do during the next reporting period to accomplish the goals?Complete serology on calves and breed all heifer calves for challenge-of-immunity at the ultimate point of gestation that the feus is susceptible to P. abortibovis (100 days gestation) to establish if long-term immunity was established wheb they were in utero.

Impacts
What was accomplished under these goals? Fifty heifers and cows were bred successfully by artificial insemination and followed up by bull breading. Pregnant animals were divided Fifty pregnant heifers were divided into 4 groups based upon prior exposure to Pajaroellobacter abortibovis: those with prior exposure and those that were naive. All animals with prior exposure were administered live P. abortibovis and all naive animals were either given live bacteria or placebo between 6 and 7 months gestation. All animals gave birth to live calves with one being relatively weak; this latter animal was born to a niave animal challenged with live bacteria, has not thrived to date, and was at the youngest fetal age of 6.5 months at the time of challenge. Serology on the calves is in progress with preliminary data demonstrating an absence of P. abortibovis-specific antibody in calves derived from non-challenged naive animals and antibody present in all calves derived from all challenged animals (naive and immune) with the highest titeres being in the calves from the naive dams.

Publications