Bovine Reproductive Disease Vaccines

Victor S. Cortese • Carole A. Bolin

As discussed earlier, cows have a multilayered placenta that leaves the fetus susceptible to infection. Infection of the placenta, inflammation of the ovary, death of the fetus, or disruption of the cervical plug all may cause abortion.

Reproductive diseases and protection against them through vaccination are areas of active research. With current research, a vaccination program can be designed to help control reproduc­tive diseases, but there is little or no research on the efficacy of many vaccines currently used to prevent reproductive disease. Given that the causes of reproductive failure are so numerous (infectious agents account for only a small percentage), vac­cination to prevent infectious reproductive losses may not appear to be effective. This is often because diagnostic testing has not been attempted or has not determined the cause of reproductive inefficiencies. A vaccination program may be inappropriately instituted when the cause is not infectious, or the current program may unfairly be deemed ineffective. Use of viral vaccines to help prevent reproductive diseases was discussed earlier in the chapter.

Brucella abortus Vaccine

Brucella vaccination has best shown the effectiveness of vac­cination in controlling a reproductive disease. Successful control and even eradication of Brucella abortus in many areas of North America are a testament to the ability of a program involving testing, culling, and vaccination to control a reproductive disease with zoonotic consequences; vaccination with either strain 19 or strain RB51 Brucella has proved to be effective.

Abortions caused by B. abortus are usually seen after 5 months' gestation. Retained placentae and subsequent metritis usually follow. The abortion is due to severe placentitis. Brucella infections have also been associated with a decrease in concep­tion rates and an increase in services per conception. A higher number of dead and weak calves has also been demonstrated in infected herds. Orchitis, seminal vesiculitis, or both may characterize infections in bulls.

Only heifer calves can be vaccinated for brucellosis. Both of the two licensed B. abortus vaccines are modified live bacterins, and vaccination of bulls may lead to orchitis.¹ Legal use of the vaccines is usually confined to heifer calves 4 to 12 months of age, because vaccination of older animals with the strain 19 vaccine may lead to false-positive results on routine Brucella screening tests. Because the strain 19 vaccine may cause septi­cemia, clinical illness, and occasionally death,² sick, unhealthy, or stressed cattle should not be vaccinated. The RB51 strain vaccine is an O antigen-deficient mutant of the B. abortus strain 2308. The RB51 vaccine has three primary advantages:

1. Antibodies induced by this vaccine do not react with the serologic tests routinely done to diagnose Brucella infections.

2. The vaccine can be used in adult cattle at a lower dosage

under special circumstances and with USDA permission.

3. The vaccine tends to cause less postvaccination fever and stress than the traditional strain 19 vaccines.

The long-term immunity conferred by Brucella vaccination is the cell-mediated type.^3,4 Calfhood vaccination does not prevent a herd of cattle from becoming infected with B. abortus, but it does largely prevent abortions and protects 65% to 75% of the cattle in the herd from infection while infected reactors are identified and slaughtered.⁵ For these reasons, in addition to vaccination, a control program should include testing and culling of all animals that test positive.

Leptospira Bacterins

Leptospirosis occurs worldwide and is caused by infection with the spirochete Leptospira. The pathogenic leptospires were formerly classified as members of the species Leptospira inter­rogans; the genus has recently been reorganized, and pathogenic leptospires are now identified in seven species of Leptospira.⁶ As part of this reclassification, the serovar names have remained the same, but some of the common leptospiral pathogens of cattle have different species names than before. The key changes for this discussion include (1) L. interrogans serovar grippotyphosa is now L. kirschneri serovar grippotyphosa; and (2) the two types of serovar hardjo have been formally split into two species: serovar hardjo type hardjobovis (found in the United States and much of the world) is now L. borgpetersenii serovar hardjo, and the less common serovar hardjo type hardjoprajitno (found primarily in the United Kingdom) is now L. interrogans serovar hardjo.

Although traditionally associated with abortions, infection with various serovars of Leptospira is associated with a variety of clinical signs, including severe systemic disease (most often in young animals), decreased milk production, birth of weak calves, and infertility. In addition, infected cattle are known to present a risk of zoonotic transmission of the infection to humans. Many different serovars of Leptospira have been shown to cause reproductive failure and abortions in cattle. Of these serovars, hardjo, pomona, and grippotyphosa''²'⁰ are more common, with serovars canicola, icterohaemorrhagiae, and bratislava occasionally implicated. The epidemiology of infection of cattle with these serovars differs with cattle serving as the reservoir or maintenance host for serovar hardjo and as an incidental host for the other serovars. In general, maintenance host infections are associated with a high prevalence of infection, a poor immune response, and long-term infection and shedding, whereas incidental host infections are characterized by low overall prevalence of infection with epidemics recognized, a vigorous immune response, and short-term infection and shedding.

Leptospirosis can cause abortion storms in which a high number of cattle may abort within a short period. There may also be an increased number of stillbirths and births of pre­mature and weak calves during these periods.¹¹ Although serovars pomona and grippotyphosa tend to cause abortions in the last trimester of pregnancy, serovar hardjo can cause abor­tions at any stage of pregnancy. Abortions are usually due to fetal infection and subsequent fetal death, although placentitis may also occur. Serovar hardjo can also colonize the oviducts and uterus,^8,2-13 diminishing fertility. After an initial serovar hardjo infection, cattle may remain infected and shed the spirochete for long periods,^14-15 whereas infection and shedding of the other serovars is relatively brief.

Current bacterins generally contain combinations of lep­tospiral serovar pomona, grippotyphosa, canicola, icterohaemor- rhagiae, and either L. interrogans serovar hardjo type hardjoprajitno or L. borgpetersenii serovar hardjo type hardjobovis. A monovalent

L. borgpetersenii serovar hardjo type hardjobovis vaccine is also available. There has been considerable debate in recent years regarding the efficacy of leptospiral bacterins for cattle. The bacterins have label claims that indicate they are to be used as an “aid in the prevention of disease.” These bacterins should therefore be expected to decrease the severity of clinical signs, including abortion, associated with infection. In general, the evidence supports such claims for serovars for which cattle are an incidental host (i.e., serovarspomona, grippotyphosa, canicola, and icterohaemorrhagiae). Protection mediated by bacterins for these serovars is thought to occur because of induction of antibodies directed against the LPS on the surface of the Leptospira.¹⁶ However, vaccination does not always prevent infection and leptospiruria caused by serovar pomona.^17-19

The efficacy of bacterins for prevention of infection, lep- tospiruria, and clinical signs associated with serovar hardjo infection is significantly more controversial. Evidence that the efficacy of traditional serovar hardjo vaccines is less than optimal includes induction of a relatively poor antibody response in vaccinated animals, the common presence of hardjo infection in herds despite routine vaccination, and experimental trials that did not demonstrate protection afforded by these traditional vaccines for prevention of infection, colonization of the renal or genital tract, or transplacental infection on challenge with

L.

Some Leptospira bacterins are labeled as single initial dose prod­ucts, but a booster dose is recommended approximately 1 month after the first dose.¹⁸ Leptospira bacterins must be administered by IM or SC injection. Although some manufacturers specify revaccination at 12-month intervals, this duration of immunity has been questioned and more frequent revaccination is often necessary to control Leptospira abortions.^19-21 A 1-year duration of immunity has been documented for two of the newer serovar hardjo bacterins, but this duration has not been documented for other hardjo vaccines or for the other serovars, making vaccination every 6 months a reasonable recommendation in many circumstances. Nevertheless, because leptospiral abortions are uncommon during the first half of pregnancy, it may be possible to use an annual vaccination schedule (serovar hardjo excepted) in seasonally calving herds like beef herds. Cattle in such herds can be vaccinated when they are 2 to 4 months pregnant, usually at the time pregnancy is diagnosed, and protected through the remainder of the pregnancy with a single annual dose.¹⁹

Prevention of leptospirosis caused by serovar hardjo requires a somewhat different approach.

Bovine Genital Campylobacteriosis Vaccines

Originally classified as Vibrio, Campylobacter fetus subsp. veneralis causes a venereal infection of cattle. The bacteria are introduced during natural breeding by infected bulls or artificial insemina­tion (AI) with infected semen. Bulls are usually infected by breeding with infected cows, but contact with infected bedding may also be a cause. Older bulls (>4 years of age) are more likely to be infected. After deposition in the vagina, the bacteria rapidly colonize the vagina and cervix and in 25% of these cows are found in the oviducts. The organism can persist for months after infection of these sites. It has been shown that fertility never returns to normal in some infected animals, and some may be permanently sterile because of the damage caused by salpingitis.

Vaccination with Campylobacter vaccines has been shown to be effective in protecting heifers even when vaginal cultures test positive for the bacteria.³⁰ It appears that the uterus is resistant to the bacteria after vaccination. Studies have dem­onstrated improved breeding efficiency in vaccinated herds.³⁰ Vaccination of bulls with oil-adjuvant vaccines not only prevents infection of bulls for up to 1 year³¹ but also aids in prevention of mechanical transfer of organisms during natural service.³² Vaccination with two doses has been shown to be effective at clearing infections from carrier bulls.^33,34

Vaccination

Use of C. fetus bacterins is recommended in all breeding herds that use bulls, even if only on selected cows. In heifer herds using virgin bulls or in 100% AI-bred herds, vaccination against Vibrio organisms is not necessary.

Several different C. fetus vaccines are available, including oil-adjuvanted and aluminum hydroxide-adsorbed types. Oil­adjuvant C. fetus bacterins have proved to be more effective³⁵ and provide longer lasting protection after a single dose.³⁶ Unfortunately, oil-adjuvant vaccines cause localized granuloma formation and fibrosis at the site of injection. This may cause visible blemishes, which may be objectionable in registered stock or show cattle. Administration no earlier than 4 months before the breeding season is preferred.³⁶ When aluminum hydroxide-adsorbed C. fetus bacterins are used, a priming dose should be administered at least 6 weeks before the immunizing (booster) dose and the booster should be administered 10 days before the beginning of the breeding season.³⁷ After administra­tion of an aluminum hydroxide-adsorbed bacterin, serum antibody concentrations peak rapidly and decline precipitously, falling to susceptible levels by 4 weeks after one dose or 11 weeks after two doses.³⁹ Some aluminum hydroxide-adsorbed bacterins do not require an initial booster.

Campylobacteriosis (vibriosis) is most effectively controlled when all breeding-age animals, including bulls, are included in the vaccination program.³² Vibrin (Zoetis) is the only C. fetus bacterin available in the United States that has been evaluated in bulls.³⁰ Two 5-mL doses are administered to breeding bulls at 4-week intervals beginning 8 weeks before the start of the breeding season.³⁰ In subsequent years, a single booster dose is administered 4 weeks before the start of the breeding season.³³ This dosage is 2.5 times that recommended for vaccination of cows.

Bovine Trichomoniasis Vaccines

Bovine trichomoniasis is a venereal infection of cattle caused by the protozoal agent Tritrichomonas foetus. Early in the course of the disease, abortions with pyometra may be seen in 5% of infected cows; these abortions occur early in gestation.³⁸ However, infertility is the most common sign, with long interservice intervals.^39,40 Early embryonic death is followed by a period of conception failure. Some natural resistance develops after infection, but carrier cows may be an important component of the epidemiology of this disease. In rare cases, uterine destruction may leave a cow sterile after an infection.⁴¹

The efficacy of Tritrichomonas vaccines is questionable,^42-45 but the vaccines do appear to reduce actual reproductive losses.⁴⁶ Heifers, cows, and breeding bulls should be vaccinated twice at 2- to 4-week intervals, the second dose given 4 weeks before the beginning of the breeding season⁴⁶; SC administration is recommended. In subsequent years a single annual booster vaccination should be given 4 weeks before the beginning of the breeding season.

In a problem herd, trichomoniasis vaccination must be coupled with other control measures like culturing, culling, and treatment to effectively control the disease.