Spirochetes: vaccines, animal models and diagnostics.

The detailed characterization of various proteins from spirochetes using molecular biology techniques has made possible new approaches to vaccine and diagnostic development that are described in this session. The importance of animal models was emphasized and illustrated.

Selective absorption of immunoglobulin IgM in the newborn calf.

The efficiency of absorption of colostral immunoglobulin classes was determined by the ratio of the quantity of immunoglobulins in the calf serum after absorption was complete to the quantity in the colostrum fed the calves. The experiment with 58 pooled colostrums assayed for absorbability of immunoglobulins had three to eight calves per assay. Colostrums with similar concentrations of immunoglobulins varied from 10 to 46% in absorption of IgG and 5 to 50% in IgA. The percent of immunoglobulin IgM absorbed increased as the amount ingested decreased. The absorption efficiencies of immunoglobulins IgA and IgG did not change as intake varied. Correlations of colostral immunoglobulins ingested with percent absorption in summaries of two experiments were -.76 and -.90 for IgM, 0 and -.33 for IgG, and -.05 and -.02 for IgA. The selective transport of IgM is important for its role as the primary immunoglobulin giving the calf immune protection during the first few days of life. The variation in absorption of IgM in different colostrums of similar immunoglobulin content was not different from that among calves receiving the same colostrum.

Colostral immunoglobulin transfer in calves. IV. Effect of suckling.

The greater absorption of colostral immunoglobulin in neonate calves suckling their dams over bottle-feeding pooled colostrum was studied to determine if age (hours postpartum) at initial feeding, amount of colostrum ingested, or mothering effect of being with the dam were responsible. Rate of absorption and maximum absorption were superior in calves that suckled, regardless of age or amount of colostrum ingested. Though the mothering effect is questionable, there is evidence that something labile is being transferred to the calf in the fresh colostrum, acting as a messenger to stimulate rapid absorptive activity in the intestinal epithelium.

Colostral immunoglobulin transfer in calves. III. Amount of absorption.

Amount of colostrum fed and age at first feeding are the two major factors in determining maximum immunoglobulin concentration in serum for each immunoglobulin class in postcolostral calves. Both factors show linear response: increasing age, decreasing concentration; increasing amount fed up to 2 liters, increasing concentration. The two factors interact in a curvilinear response. Calves with initial feeding at progressively older ages need less colostrum to reach maximum absorption. Maximum absorption is represented by a progressively lower immunoglobulin concentration in serum with increasing age. Response surface contours for the maximum immunoglobulins IgG, IgM, and IgA, based on experimental data, have been included. Neither body weights of the experimental calves nor pooled colostral concentrations of immunoglobulin from pooled colostrums fed to the calves influenced maximum concentrations of immunoglobulin in serum.

Colostral immunoglobulin transfer in calves I. Period of absorption.

Termination or closure of intestinal permeability to colostral immunoglobulins in the calf occurs spontaneously with age at a progressively increased rate after 12 h postpartum. Following a normal distribution, mean closure occurred near 24 h postpartum when the calves were not fed. Feeding colostrum shortly after birth resulted in earlier cessation of absorption. The amount of colostrum fed had no influence on closure. A quadratic response surface analysis of starting time on closure showed a significant linear response in all immunoglobulin classes, indicating that as colostrum feeding is delayed, cessation also is delayed up to the time of spontaneous closure. Differences in closure time for the three immunoglobulin classes were not significant.

Colostral immunoglobulin transfer in calves II. The rate of absorption.

The rate and pattern of colostral immunoglobulin absorption, based upon increase in concentration of immunoglobulin in serum in calves, has been determined from the interaction of three factors: starting age of colostral feeding, amount of colostrum fed, and time after feeding. All immunoglobulin classes show common characteristics of absorption following a rapid transfer during the first 4 h after feeding. An analysis of three-dimensional response surface for each of the three immunoglobulin classes indicated positive linear trend in the amount fed up to 2 liters. Rates of absorption in succeeding time periods following the initial feeding had decreasing linear trends. That is, age at first feeding had an inverse effect on rate of absorption. A linear-by-linear interaction between amount fed and starting age as shown for all three classes. Only immunoglobulin IgM had a significant quadratic response for amount fed. Concentration of immunoglobulin in the pooled colostrums fed had no influence on rate of absorption. Evidence is that 2 liters of colostrum fed to Holstein calves may be optimum in the range studied for maximum pinocytotic activation of absorptive cells and maximum rate of absorption.

Influence of environment on passive immunity in calves.

Passive immunity in neonatal calves is influenced by environment. Placing newly born Holstein calves (108 head) in three different housing environments (shade, cooled shade, hutch) during hot weather produced differences in body temperature, serum cortocosteroids, immunoglobulin IgG1 concentrations, and mortality. Experimental design permitted examination of effects due to treatments, time, differences in colostrum, and climatic environment in an analysis of variance. Calves exposed to the hotter, less desirable environment responded by having a higher mortality, higher serum corticosteroid concentration, and lower serum immunoglobulin IgG1 at 2 and 10 days after birth. All of these were correlated. Calves that died had serum immunoglobulin IgG1 falling below the mean for all experimental calves.

Growth-inhibiting antibody responses of humans vaccinated with recombinant outer surface protein A or infected with Borrelia burgdorferi or both.

Serial serum samples from a 2-year human trial of outer surface protein (Osp) A vaccine were analyzed by Borrelia burgdorferi growth-inhibition assay (GIA) and anti-OspA ELISA to assess the antibody responses of vaccine recipients and subjects with Lyme disease. Although 74% of OspA recipients had a reciprocal GIA titer >/=64 after 3 vaccinations, none of the placebo recipients, even those with Lyme disease, had a GIA titer this high. The correlation between GIA and ELISA titers after 3 doses of vaccine was.84; however, more vaccine recipients had an elevated ELISA titer paired with low GIA titer than had a low ELISA titer with a high GIA titer. OspA-vaccine recipients who acquired Lyme disease had significantly lower serum GIA and ELISA titers after 3 immunizations than did age- and sex-matched OspA recipients without Lyme disease. Thus, vaccinated subjects had antibodies to native antigen on viable cells, and antibody assays with this specificity may predict protection of vaccinees against infection.