Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Bacterium or component thereof or substance produced by said...
Reexamination Certificate
1999-03-10
2002-04-30
Graser, Jennifer E. (Department: 1641)
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Bacterium or component thereof or substance produced by said...
C424S184100, C424S240100, C424S241100, C424S256100, C424S258100, C424S264100, C424S232100, C426S002000, C426S335000, C426S532000, C426S302000
Reexamination Certificate
active
06379676
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
A method for enhancing the effectiveness of vaccines in animals, by maintaining the animals on a diet of contamination-resistant feed.
2. Discussion of the Background
Livestock such as poultry, swine, cattle and horses are routinely treated with vaccines to prevent viral and bacterial diseases. Breeders are sometimes vaccinated for another reason, to provide passive immunity to their offspring by supplying antibodies through colostrum in the case of mammals, and through egg yolk in the case of birds. Because neonatal animals have underdeveloped immune systems, passive immunity is their main source of protection against viral and bacterial diseases.
It is known that animal feed can be rendered highly resistant to contamination by pathogens, by spraying it with formaldehyde using an atomizing spray technique disclosed by Bland et al., U.S. Pat. No. 5,505,976 and divisional U.S. Pat. No. 5,591,467, both incorporated herein by reference. It was also disclosed that animals maintained on such feeds are more productive, in terms of feed conversion efficiency. It has now been discovered that animals which are maintained on a diet of contamination-resistant feedstuffs respond more strongly when immunized against diseases, with anti-viral vaccines and anti-bacterial vaccines (bacterins). Also, transference of passive immunity to offspring is enhanced by maintaining a breeder on contamination-resistant feedstuffs, providing a method for improving the health of neonatal animals.
SUMMARY OF THE INVENTION
An object of the invention is to provide a method for improving the immune response of an animal to a vaccine by maintaining it on a diet of contamination-resistant feed and treating the animal with an anti-viral or anti-bacterial vaccine.
Another object of the invention is to provide a method for increasing the level of antibodies in eggs, colostrum or milk produced in response to vaccination, by maintaining a breeding animal on a diet of contamination-resistant feed, and treating the breeding animal with an anti-viral or anti-bacterial vaccine.
Another object is to improve the absorption of antibodies by neonatal animals from egg yolk, colostrum or milk, by maintaining a breeding animal on a diet of contamination-resistant feed, vaccinating the breeder with an effective amount of an anti-viral or anti-bacterial vaccine and administering the resulting egg yolk, colostrum or milk to a neonatal animal.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
When an animal is maintained on a diet of contamination-resistant feedstuffs, produced by treatment with formaldehyde in accordance with the methods of Bland et al., subsequent vaccinations of the animal with standard anti-viral and anti-bacterial vaccines are more effective because the amount of antibodies produced by the animal increases significantly. In the case of breeding animals the amount of antibodies deposited in the egg yolk, milk or colostrum also increases, which is of benefit to the offspring.
Preparation of Contamination-Resistant Feedstuffs
Applying formaldehyde to animal feed to kill Salmonella was known before the method of Bland et al., however, previously the goal was merely to provide an immediate killing effect. Formaldehyde solutions were mixed thoroughly with the feed in sufficient quantity to kill the Salmonella, using the same spray equipment ordinarily used to apply mold inhibitors. Such spraying equipment is designed to produce a coarse spray, i.e., droplet sizes in the range 260-400 microns, to decrease energy requirements and increase the application rate. The need to distribute formaldehyde throughout the feed was understood, because more than 99% of the Salmonella should be killed to prevent it from quickly recontaminating the feed. Coarse spraying with large amounts of formaldehyde is adequate for that purpose. Bland et al. discovered that when aqueous formaldehyde is sprayed onto feed in the form of a mist, using an atomizing sprayer, the resulting feedstuff is substantially more resistant to recontamination by pathogenic bacteria than feed treated with the same quantity of formaldehyde using conventional spray nozzles. In each case all of the bacteria are killed immediately, but the misting method produces a strong residual killing effect. It was also observed that much less formaldehyde is necessary to obtain equivalent resistance levels, in terms of the time a sample can resist challenge under aerobic conditions with
E. coli
or Salmonella.
It is possible to characterize a difference in physical properties between contamination-resistant feeds used in the present invention and feeds treated with formaldehyde using conventional spray nozzles. The quantity and distribution pattern of a formaldehyde adduct in the feed can be measured using an acidic hydrolysis assay. A highly uniform distribution of adduct, expressed in terms of the coefficient of variation (CV), is related to the feed's contamination resistance.
The formaldehyde adduct's distribution pattern through the feed is controlled by the size of spray droplets used to apply the formaldehyde, the thoroughness and speed of mixing the feed during the application process, the rate at which the formaldehyde solution is applied, and the residence time of feed in the mixer. A compromise must be reached with regard to some conflicting variables. For instance, it is desirable to move feed through the mixer as quickly as possible for economic reasons, but too short a residence time results in inadequate mixing even if the flow rate of formaldehyde solution is increased. The residence time in a two-ton (1814.4 kgs) horizontal mixer is typically three to five minutes. The formaldehyde solution should be delivered at a rate of 20-40 gal/hr. (75.5-151.4 liters/hr.). The size of spray particles is preferably small, 20-80 microns. However this range limits flow rate and may require several nozzles. Larger spray sizes, up to about 250 microns, can also be effective if other variables are adjusted to compensate, such as increased mixing rate or residence time, increased amounts of formaldehyde solution, or accepting a decreased resistance to contamination of the finished feed. Typically the best compromise will be a spray particle size in the 10-200 micron range. Suitable application rates for 1 kg of solution per metric ton of feed span the range of 15-90 seconds, preferably 45-60 sec.
The coefficient of variation should be 7% or less to achieve significant resistance to pathogenic bacteria, preferably 5% or less. The term “resistant to contamination by pathogenic bacteria” means that a challenge with 1000 colony forming units (CFU) per gram of feed results in the death of substantially all the bacteria within 24 to 72 hours. In particular, the term “resistance to contamination by Salmonella or
E. coli
” means that a challenge with 1000 CFUs of Salmonella or
E. coli
per gram of feed results in 1 CFU or less per 25 grams of feed after 24 hours incubation at 25° C. A value of 5% CV or less allows reduced quantities of formaldehyde to be maximally effective. Also, such uniform formaldehyde distribution results in much less emission of formaldehyde vapor from the freshly treated feed and appears to increase the yield of adduct. Bacterial resistance is a function of the coefficient of variation. At 7% CV, the product will have relatively low resistance, which also varies according to the quantity of formaldehyde applied. At 4 lbs. (1.81 kg) dry wt. of formaldehyde per metric ton of finished feed a 7% CV results in about 30 days resistance as measured by challenge with
E. coli
(1000 CFU/gram of feed). Conversely, at 2.0% CV and only 2 lbs. (0.91 kg) dry wt. of formaldehyde/metric ton, a finished feed will resist contamination by
E. coli
(1000 CFUs/gram of feed) for about 60 days.
The increased bacterial resistance of feedstuffs according to the invention can be seen in the following experiment reported in Bland et al., U.S. Pat. No. 5,505,976. A sterilized poultry starter mash (500 grams/treatment quan
Anitox Corporation
Graser Jennifer E.
Pillsbury & Winthrop LLP
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