The effect of age on the immune response of horses to vaccination.

Few studies have investigated immunosenescence in the horse, but it is accepted that the primary and secondary (anamnestic) immune responses may differ between aged and younger horses. The aim of the present study was to determine whether aged horses have a protective immune response post-vaccination. Thirty-four aged healthy horses (> or =20 years) and 29 younger adult horses (4-12 years) of various breeds were vaccinated with commercially produced killed rabies and influenza vaccines. Rabies serum neutralizing antibody titres and equine influenza virus specific antibody subclasses (immunoglobulin IgGa and IgGb) and single radial haemolysis titres were determined. Healthy aged horses mounted a primary immune response to rabies vaccine that was similar to that of younger adult horses. However, aged horses had a significantly reduced anamnestic response to influenza vaccination in comparison with the younger adult horses, even though the pre-vaccination antibody titres of aged horses were higher. Rabies antibody titres in both groups declined significantly by 6 months post-vaccination. Serum concentrations of selenium (Se) and vitamin E were measured to test for potential confounding effects. Significant numbers of horses had suboptimal serum Se concentrations, but Se status had no significant impact on antibody production after vaccination.

The effect of age on serum antibody titers after rabies and influenza vaccination in healthy horses.

BACKGROUND: The proportion of geriatric horses within the equine population has increased in the past decade, but there is limited information on the immune function of these animals. HYPOTHESIS: Aged horses will have a lesser increase in serum antibody response to vaccination. ANIMALS: Thirty-four aged healthy horses (> or = 20 years) and 29 younger adult horses (4-12 years) of various breeds. METHODS: All horses were vaccinated with vaccines of killed rabies and influenza virus. Horses in each age group were allocated to receive either rabies or influenza booster vaccine 4 weeks after the initial vaccination. Serum samples were taken at 0, 4, 8, and 24 weeks. Rabies serum neutralization titers and equine influenza virus specific antibody sub-isotypes (IgGa, IgGb, IgG(T), and IgA) as well as single radial hemolysis (SRH) titers were determined. RESULTS: Rabies antibody titers were similar in the 2 age groups at all sampling times. Aged horses had higher IgGa and IgGb influenza antibody titers before vaccination than younger horses but similar titers after vaccination (P= .004 and P= .0027, respectively). Younger horses had significantly greater increases in titer than aged horses at all sampling times for IgGa (P= .001) and at 8 and 24 weeks for IgGb (P= .041 and .01, respectively). There was no detectable serum IgG(T) at any time point. A significant booster vaccine effect was seen for both antirabies and anti-influenza titers. Anti-influenza titer before vaccination also had a significant effect on subsequent antibody response. CONCLUSIONS AND CLINICAL IMPORTANCE: Healthy aged horses generated a primary immune response to a killed rabies vaccine similar to that of younger adult horses. Aged horses had a significantly reduced anamnestic response to influenza vaccine.

Foals are interferon gamma-deficient at birth.

The increased vulnerability of foals to specific pathogens such as Rhodococcus equi is believed to reflect an innate immunodeficiency, the nature of which remains poorly understood. Previous studies have demonstrated that neonates of many species fail to mount potent Th1 responses. The current research investigates the ability of circulating and pulmonary lymphocytes of developing foals to produce interferon gamma (IFNgamma). Peripheral blood mononuclear cells (PBMC) were prepared from up to 10 horse foals at regular intervals throughout the first 6 months of life. Bronchoalveolar lavage (BAL) samples were collected at 1, 3 or 6 months of age from three groups of five foals. The PBMC and BAL cells were stimulated in vitro and IFNgamma production was measured by intracellular staining. In addition, RNA was extracted from freshly isolated and in vitro stimulated PBMC and BAL cells for quantitation of IFNgamma gene expression by real time PCR. Newborn foals exhibited a marked inability to express the IFNgamma gene and produce IFNgamma protein. This deficiency was observed in both circulating and pulmonary lymphocytes. However, IFNgamma gene expression and protein production increased steadily throughout the first 6 months of life, reaching adult levels within the first year of life. These findings suggest that foals are born with an inherent inability to mount a Th1-based cell mediated immune response which may contribute to their susceptibility to intracellular pathogens.

Passive transfer of maternal immunoglobulin isotype antibodies against tetanus and influenza and their effect on the response of foals to vaccination.

Influenza and tetanus-specific antibodies of the IgG sub-isotypes are posively transferred to foals via colostrum and inhibit their response to inactivated influenza vaccines and tetanus toxoid. High titres of influenza antibodies of IgGa and IgGb subisotypes and tetanus antibodies of the IgGa, IgGb and IgG(T) subisotypes were detected in postsucking serum samples collected from foals born to mares that had received booster doses of multicomponent vaccines during the last 2 months of gestation. Thereafter, titres declined in an exponential manner but were still detectable in all foals at age 26 weeks, regardless of whether they had been vaccinated prior to age 26 weeks. Mean +/- s.e. half-life of decline of influenza IgGa antibodies (27.0 +/- 2.3 days) was significantly shorter than that of influenza IgGb antibodies (39.1 +/- 2.7 days; P<0.005). Tetanus IgGa and IgGb antibodies declined with half-lives of 28.8 +/- 3.0 and 34.8 +/- 5.1 days, respectively. Titres of tetanus IgG(T) antibodies were substantially higher than those of influenza IgG(T) antibodies in postsucking samples and remained so through age 26 weeks, declining with a half-life of approximately 35 days. Postsucking titres of tetanus and influenza antibodies of the IgA isotype were low and declined rapidly to undetectable levels. Yearlings showed significant increases in titre of influenza IgGa, IgGb and IgG(T) subisotype antibodies but no increase in influenza IgA antibodies in response to 2 doses of multicomponent vaccines containing tetanus toxoid and inactivated influenza A-1 and A-2 antigens. Yearlings also showed strong tetanus IgGa, IgGb and IgG(T) subisotype responses to one dose of vaccine and a substantial further rise in titre in response to administration of a second dose 3 weeks later, but failed to show an increase in titre of tetanus IgA antibodies. The influenza and tetanus IgGa, IgGb and IgG(T) subisotype responses of 6-month-old foals to vaccination followed the same pattern as those shown by yearlings but titres were generally lower. In contrast, 3-month-old foals failed to show increases in titre of either influenza or tetanus IgG subisotypes in response to 2 doses of vaccine and generally needed 1-3 additional booster doses of vaccine to achieve titres similar to those achieved by yearlings after 2 doses. Based on the finding that maternal antibodies exert a significant inhibitory effect on the response of foals to tetanus toxoid and inactivated influenza antigens, it is recommended that primary immunisation of foals born to vaccinated mares should not commence before age 6 months.

Effect of colostral ingestion on immunoglobulin-positive cells in calves.

The importance of colostrum for passive transfer of maternal immunoglobulin in calves is well established. Colostrum is thought to have additional generalized and antigen-specific immunomodulatory activities, of which the downregulation of endogenous immunoglobulin production is best documented. The objective of this study was to examine whether ingestion of colostrum altered the B cell subpopulations in the lymph nodes of newborn calves. Calves were fed one gallon of either fresh colostrum (Group A, n = 5), milk replacer (Group B, n = 5) or treated (frozen or irradiated) colostrum (Group D, n = 4) and were euthanized at 36-48 h. An additional 5 calves (Group C, 3 newborn and 2 mid-term fetuses) did not receive any feedings; the neonatal calves were euthanized immediately following birth. Mesenteric and regional lymph nodes from all calves were analyzed by immunocytochemistry using monoclonal antibodies recognizing bovine IgA, IgG1, IgG2, and IgM. Calves from Groups B and C (colostrum deprived, neonates, and fetuses) showed a consistent pattern of IgG1 and IgG2 positive cells scattered individually and in clusters throughout lymph node cortex, paracortex, and cortico-medullary junction. In sharp contrast, no IgG1 and IgG2 positive cells were present in the lymphoid tissues of colostrum fed calves (Groups A or D). Numbers of IgM and IgA positive cells were similarly distributed in all calf groups. These findings demonstrate that colostrum feeding reduces the number of immunoglobulin positive cells in the lymphoid tissues of newborn calves in an isotype-specific manner. This results in the elimination of IgG1 and IgG2 positive cells that are present in both fetuses and newborn calves. This effect is not eliminated by freezing or irradiation, indicating that a non-cellular, cold-stable colostral factor is responsible. Systemically distributed colostral proteins such as immunoglobulin or cytokines are the most likely mediators. The significance of this phenomenon in terms of colostral modulation of calf endogenous antibody production is discussed.

A study of bovine and equine immunoglobulin levels in pony foals fed bovine colostrum.

As part of a project to raise specific pathogen free (SPF) Welsh Mountain Pony foals, free from exposure to Equid herpesvirus type 1, foals were removed from their dams at birth and fed bovine colostrum. This study characterises the uptake of bovine colostral immunoglobulin and production of endogenous immunoglobulin, in 10 SPF foals. An enzyme-linked immunoadsorbent assay was developed to measure serum concentrations of bovine IgG1 (boIgG1) to assess the efficiency of transfer, and rate of elimination of boIgG1 by the foal. The endogenous production of equine IgG was studied using a single radial immunodiffusion test. Foals were given 1.2 to 2 litres of bovine colostrum achieving peak serum boIgG1 concentrations of 18.9 to 34.2 g/litre (mean 28.0). The mean half-life of boIgG1 in the foals was 7.4 days. Endogenous immunoglobulin production resulted in equine IgG concentrations greater than 2 g/litre in six of 10 foals by 14 to 19 days of age, and greater than 7 g/litre in eight of 10 foals by 37 to 50 days of age. All foals had equine IgG serum concentrations greater than 10 g/litre by 102 to 135 days of age.

The raising of equine colostrum-deprived foals; maintenance and assessment of specific pathogen (EHV-1/4) free status.

Over a period of two years, a total of 22 full term foals from Welsh Mountain pony mares were raised in conditions that were free from infection by Equid herpesvirus (EHV-1/4). Parturition dates were predicted by monitoring colostrum electrolytes, and the mares allowed to foal naturally under supervision or following induction with intravenous oxytocin. Immediately following birth, foals were separated from their dams and transferred to a specially built, positive pressure isolation unit. They were given antibiotic prophylaxis and fed bovine colostrum during the first 24 h, and then mare's milk replacer until weaned. Out of 22 specific pathogen free (SPF) foals one that had not been given antibiotic prophylaxis died of an E. coli septicaemia aged eight days. Two foals developed a streptococcal upper respiratory tract infection, which responded to antibiotic therapy and did not spread to the rest of the herd. A self limiting upper respiratory tract infection was seen in a fourth foal and mild diarrhoea was observed in six foals. Physical development in all SPF foals appeared normal and behavioural patterns resembled those of conventional handreared foals. Newborn foals were held in a separate quarantine area, within the isolation unit, and checked extensively for evidence of EHV-1/4 infection, before being transferred to the main holding unit. Periodic checks were then made for EHV-1/4 over a period ranging from 2 to 4 months; none of the SPF foals showed evidence of infection with EHV-1/4 in terms of clinical disease, virus isolation, sero-conversion or specific lymphocyte transformation.