Bacterial Scours Vaccines
Gerald E. Duhamel • Victor S. Cortese
Enterotoxigenic Escherichia coli
(Calf Scours) Bacterins
Neonatal calf diarrhea associated with enterotoxigenic E. coli (ETEC) usually occurs within the first 72 hours of life.
The majority of ETEC-associated NCEDs are associated with strains that produce the F5 (K99) fimbrial adhesin mediating adherence to specific receptors located on the brush border of small intestinal villous enterocytes, thereby resisting normal peristaltic clearance mechanisms, and thus, promoting bacterial colonization of the intestinal mucosa.1-3 Adherent ETEC produce enterotoxins that stimulate water and electrolyte loss into the intestinal lumen, leading to dehydration and electrolyte imbalance that can be fatal. These ETEC strains may also express other types of fimbriae, including F41 and F1 (type 1), sometimes in combinations with the same strain of ETEC.1,4 Intestinal colonization and villous attachment by strains of ETEC expressing adhesive fimbriae can be prevented by precalving vaccination of the dam with a bacterin that contains a single fimbrial antigen in common with the challenge strain.1,4 However, disease may occasionally be caused by ETEC expressing fimbrial antigens different from the most common, F5+; therefore typing of E. coli isolates obtained from diarrheic calves can assist with proper selection of an ETEC fimbriae- based vaccination program.5,6Because calf scours associated with ETEC strains occurs so early in life, there is not enough time for a newborn calf to mount a protective immune response through vaccination. Therefore control of ETEC-induced calf scours is aimed at (1) limiting calf exposure to bacterial pathogens, (2) vaccinating dams to provide high levels of fimbriae-specific colostral antibodies (i.e., usually against the F5 antigen), and (3) providing adequate volume of colostrum as soon as possible after birth to prevent bacterial colonization of the calf intestinal tract.3 Pregnant cows are vaccinated in late gestation to ensure high concentrations of anti-F5 colostral antibodies.
When colostrum from vaccinated cows is fed to newborn calves, the antibodies prevent bacteria expressing fimbrial adhesin from binding to specific host cell receptors located on the brush border of small intestinal villous enterocytes, mostly in the jejunum and ileum.1,8 Unbound ETEC bacteria are passed into the feces by intestinal peristalsis and, thus, prevented from colonizing the small intestine and causing disease. By 72 to 96 hours of age, calves are highly resistant to ETEC infection and will rarely show clinical signs of diarrhea.1,9 Thus, feeding calves colostrum with a high concentration of antibodies against F5 fimbrial antigen, even though restricted to the first day of life, is often sufficient to prevent severe diarrheal disease.4 Passive circulating serum antibodies that are absorbed into the bloodstream from the intestinal tract are thought to play little or no role in protective immunity against NCED caused by ETEC.1 However, for maximum efficacy of ETEC vaccine programs, a concurrent well-managed colostrum program should be in place.Nearly all strains of ETEC that have been isolated from neonatal calves have F5 fimbriae. Currently there is no evidence that a bacterin with multiple types of fimbrial antigens is more effective than products with only F5, so long as the vaccine and challenge strains share a common fimbrial antigen.1 However, vaccines with multiple fimbrial antigens are more likely to have at least one of the antigens expressed by the challenge ETEC strain. Besides non-F5 ETEC strains potentially causing calf scours, a lack of efficacy of fimbriae-based ETEC vaccines may be due to E. coli belonging to a pathotype other than ETEC, including attaching and effacing E. coli (AEEC) and Shiga toxin-producing E. coli (STEC), which cause hemorrhagic enterocolitis in 1- to 6-week-old calves. Given that AEEC and STEC strains do not produce fimbrial adhesins, fimbriae-based ETEC bacterins will not protect against these strains.6,7 Unfortunately, commercially available vaccines for prevention of calf scours associated with AEEC and STEC are not currently available.
Escherichia coli Vaccination Programs
The general recommendations for use of fimbriae-based ETEC vaccines (bacterins) are summarized in Table 48.10. ETEC bacterins are offered as single-antigen vaccines and in combination with other antigens designed to protect against other diseases in addition to ETEC infection. Oil-adjuvanted ETEC bacterins are administered by IM injection in a single dose 2 weeks to 6 months before calving, and administration is repeated annually.10 Non-oil-adjuvanted ETEC bacterins are recommended for IM or SC injection in two doses administered at a 2- to 4-week interval, with the second dose given 3 to 6 weeks before calving. In subsequent years a single booster dose should be administered 3 to 6 weeks before calving. ETEC bacterins do not protect calves that do not ingest adequate amounts of colostrum soon after birth. Also, because this protection is based on passive immunity, high environmental challenge levels may overwhelm the limited amount of antibodies present in the lumen of the calf's small intestine. This is consistent with the higher prevalence and severity of clinical ETEC infections in the offspring of replacement dairy heifers kept in overcrowded closed confinement than in less intensive cow-calf beef operations. Environmental control of bacterial contamination is paramount to effective NCED management.
■ TABLE 48.10
Currently Licenseda Escherichia coli Bacterin Toxoids, Salmonella Bacterins, and Core Endotoxoid Vaccines
| Antigens | Vaccine | Vaccination Regimen | Manufacturer |
| Escherichia coli | |||
| K99 | Pili Shield | 1 dose 2 weeks before calving | Novartis Animal Health (Larchwood, IA) |
| K99 | ScourGuard 3(K) | Year 1: 2 doses 6 weeks and 3 weeks before calving Subsequent years: 1 dose 3-6 weeks before calving | Zoetis (Florham Park, NJ) |
| Salmonella | |||
| Salmonella Typhimurium | POLY-BAC B SOMNUS | 2 doses 2 weeks apart | Texas Vet Lab (San Angelo, TX) |
| Salmonella Dublin and S. Typhimurium | Salmo-Shield TD | 2 doses 2-4 weeks apart | Novartis Animal Health (Larchwood, IA) |
| SDT-Guard | 2 doses 2-4 weeks apart | Boehringer Ingelheim (St. Joseph, MO) | |
| Salmonella Dublin/ Typhimurium Bacterin | 2 doses 2-3 weeks apart | Colorado Serum Company (Denver, CO) | |
| Salmonella Dublin | Salmonella Dublin Modified | 2 doses 2 weeks apart; start at | Boehringer Ingelheim |
| Live EnterVene-d | age 2 weeks or older | Vetmedica (St. Joseph, MO) | |
| Salmonella Core Antigens | |||
| J-5 E. coli mutant endotoxin core | J-VAC | Year 1: 2 doses 2-4 weeks apart Subsequent years: 2 doses 2-4 weeks apart | Merial (Iselin, NJ) |
| Enviracor j-5 | Year 1: 3 doses starting 8 weeks and 4 weeks before calving and 2 weeks after calving | Zoetis (Florham Park, NJ) | |
aLicensed by the Animal and Plant Health Inspection Service, U.S. Department of Agriculture, as of 2018.
Salmonella Vaccines
Salmonellosis is due to infection by various pathogenic Salmonella enterica serotypes (see Chapter 32). Disease severity varies according to serotypes and strain-specific virulence determinants, but also according to the number of infective organisms, route of entry, and host natural and acquired resistance mechanisms. Bovine salmonellosis is caused predominantly by S.
enterica serotypes Typhimurium (S. Typhimurium) and Dublin (S. Dublin), and although both serotypes can cause enteritis, clinical disease associated with each serotype is different. Disease caused by S. Typhimurium, a ubiquitous group B Salmonella serotype, is most often associated with enteritis resulting in diarrhea in young calves. The host-restricted serotype group D S. Dublin most often causes systemic infections that may result in asymptomatic shedding or abortion in pregnant cows. Consequently, commercially available Salmonella vaccines contain single or combinations of S. Typhimurium and Dublin. Because Salmonella serotype Newport and other group C Salmonella have increased in prevalence, serotyping of Salmonella is critical to implementing an effective vaccination program. All currently licensed products are formalin-inactivated, whole-cell, aluminum hydroxide-absorbed bacterins, except for a genetically altered, stable, nonreverting, aromatic-dependent (aroA mutant) modified live S. Dublin vaccine (Entervene-D [Boehringer Ingelheim Vetmedica Inc., St. Joseph, Mo.]) and a siderophore receptor protein (SRP)-based vaccine (SRP S. Newport Vaccine, Conditional USDA License [Zoetis, Parsippany, NJ]). One S. Typhimurium and three E. coli mutant lipopolysaccharide (LPS) core antigen vaccines can provide protection from morbidity and mortality associated with salmonellosis.A modified live and genetically altered (via deletion of aroA) S. Dublin vaccine marketed for parenteral use is effective in 2-week-old calves against challenge with S. Dublin, but it also provides cross-protection to challenge with S. Typhimurium.12,13 As with many gram-negative bacterial vaccines, adverse reactions to this vaccine have been reported. Anecdotal reports of effective oral use in calves younger than 2 weeks old indicate that this route may help avoid some adverse reactions associated with injection of an endotoxin-containing product. Killed Salmonella bacterins can produce measurable serum antibody responses to bacterial proteins in calves and adult cattle.
However, calves vaccinated with a killed bacterin are unable to produce anti-LPS antibodies until 12 weeks of age, and optimum responsiveness does not occur until a year old. Most controlled studies in which calves were vaccinated with a killed Salmonella bacterin and orally challenged have reported a lack of protection.16-18 One small study that reported good protection after vaccination of 3- to 6-week-old calves with two doses of killed bacterin used IM challenge. Another study in 6-month-old cattle found that a single intradermal dose of heat-killed S. Dublin protected against IV challenge. Vaccination of cattle 3 months of age or older with two doses of killed Salmonella bacterins can prevent salmonellosis. Although little has been published on the efficacy of a conditionally USDA-licensed SRP S. Newport vaccine, the clinical impression is that it is safe and effective at reducing fecal shedding of Salmonella but also capable of controlling disease caused by different serotypes of Salmonella.Vaccination of adult cows, with passive transfer of antibody to calves through colostrum, is frequently used in dairies to control salmonellosis in neonates. Controlled trials evaluating passive protection have produced mixed results, with some indicating a lack of protection18,21 and others demonstrating some protection in 5-day-old calves. Vaccination of dry cows may be useful for control of salmonellosis in calves younger than 3 weeks of age but is minimally effective for controlling salmonellosis in calves older than 3 weeks. There are anecdotal reports of protection against salmonellosis by repeated vaccination of calves with an S. Typhimurium mutant LPS core antigen vaccine (ENDOVAC [IMMVAC Inc., Columbia, Mo.]). A J-5 E. coli Rc-mutant LPS core antigen-based bacterin (J-VAC [Merial Ltd., Athens, Ga.], ENVIRACOR J-5 [Zoetis], and Hygieia [Biological Laboratories, Woodland, Calif.]) improve survival and reduce morbidity rate from naturally occurring bacterial infections in dairy calves vaccinated at 3 and 17 days of age.
Gram-Negative Mutant Lipopolysaccharide Core Antigen Bacterins
■ TABLE 48.11
Currently Licensed Vaccines for Prevention of Calf Scour Associated With F5 (K99) Enterotoxigenic Escherichia coli Infection and Disease Associated With Salmonella enterica
| Antigen | Vaccine Name | Vaccination Regimen | Manufacturer |
| E. coli F5 (K99) Vaccines | |||
| F5 (K99 [bacterin]) | Bovine Pili Shield | Year 1: 1 dose 8-16 weeks before calving Subsequent years: 1 dose before calving | Novartis Animal Health (Larchwood, IA) |
| F5 (K99 [cell-free | Guardian | Year 1: 2 doses up to 12 weeks and approximately 3-6 | Intervet Inc./Merck |
| extract]) | weeks before calving Subsequent years: 1 dose up to 5-7 weeks before calving | Animal Health (Omaha, NE) | |
| F5 (K99 [bacterin]) | ScourGuard 4KC | Year 1: 2 doses 6-9 weeks and 3-6 weeks before calving Subsequent years: 1 dose 3-6 weeks before calving | Zoetis (Florham Park, NJ) |
| F5 (K99) (4 strains | bgcolor=white>Scour Bos 9Year 1: 2 doses 8-16 weeks and 4 weeks before calving | Novartis Animal | |
| [bacterin]) | Subsequent years: 1 dose up to 8-10 weeks before calving | Health (Larchwood, IA) | |
| Salmonella Vaccines | |||
| Salmonella enterica | POLY-BAC B | 2 doses 2 weeks apart | Texas Vet Lab (San |
| serotype Typhimurium | SOMNUS | Angelo, TX) | |
| (bacterin-toxoid) | |||
| S. enterica Dublin/ | S. Dublin- | Adults: 2 doses 2-3 weeks apart before placement on | Colorado Serum |
| Typhimurium | Typhimurium | feed, and pregnant cows 4-6 weeks before calving | Company (Denver, |
| (bacterin) | bacterin | Newborn calves >7 days of age: 2 doses 2-3 weeks apart | CO) |
| S. enterica Dublin/ Typhimurium (bacterin) | SDT-Guard | Adults: 2 doses 2-4 weeks apart | Boehringer Ingelheim Vetmedica, Inc. (St. Joseph, MO) |
| S. enterica Newport | Salmonella | 6-month-old and older: 2 doses 2-4 weeks apart | Zoetis (Florham |
| (siderophore receptor protein [SRP]; | Newport Bacterial Extract | Park, NJ) | |
| conditional USDA license | |||
| S. enterica serotype Dublin (modified live) | EnterVene-d | 2 weeks of age and older: 2 doses 12-16 days apart | Boehringer Ingelheim Vetmedica, Inc. (St. Joseph, MO) |
| Salmonella/E. coli Mutant LPS Core Antigen Vaccines | |||
| S. enterica serotype | ENDOVAC-Dairy | Cows during dry period and heifers during third trimester of | IMMVAC Inc. |
| Typhimurium (bacterin-toxoid) | ENDOVAC-Beef | pregnancy: 2 doses 2-3 weeks apart Subsequent years: 1 dose Year 1: 2 doses 2-3 weeks apart Subsequent years: 1 dose | (Columbia, MO) |
| J-5 E. coli | J-VAC (bacterin- | Year 1: 2 doses 2-4 weeks apart | Merial LTD (Athens, |
| toxoid) | Subsequent years: 2 doses 2-4 weeks apart Pregnant cows: 2 doses starting at 7 months of gestation or at dry off and 1-3 weeks before calving | GA) | |
| Enviracor j-5 | Cows or heifers: 3 doses starting at 7 and 8 months of | Zoetis (Florham | |
| (bacterin) | gestation and 2 weeks after calving | Park, NJ) | |
| E. coli bacterin | 3 doses 4-6 weeks apart | Hygieia Biological Laboratories (Woodland, CA) | |
| Bovilis j-5 E. coli bacterin | 3 doses 4-6 weeks apart | Merck Animal Health (Madison, NJ) | |
are exposed to and infected with Salmonella in the first week or two after birth. Salmonellosis in dairy calves often occurs after 2 weeks of age. However, when vaccinated at age 3 and 10 days with an oil-adjuvant J-5 E. coli bacterin, calves do develop strong antibody responses by 17 days of age; this strong antibody response occurs even in the presence of passively acquired antibodies to LPS core antigens.30 Consequently, a combined program in which both dry cows and neonatal calves are immunized against LPS core antigens might be a useful approach for reducing the severity of salmonellosis in neonatal dairy calves.