ARCHIVE FILE
This article was published in 1964
See the original document
INSTITUTE OF INSPECTORS OF STOCK OF N.S.W. YEAR BOOK.
The Control of Virus Diseases of Livestock By Means of Vaccines
E. L. FRENCH, M.Sc., Ph.D. Division of Animal Health, Animal Health Research Laboratory, C.S.I.R.O. Parkville, Victoria
To those of us interested in infectious diseases, the term "immunity" generally means a heightened resistance to the pathological effects of infection with a microorganism. This resistance or immunity follows the infection, or other means of contact, of the animal with the disease agent. For the most part, immunity to infectious disease is correlated with bodies in the blood stream, and there are a number of laboratory tests which have been developed to measure antibodies in serum. With bacterial diseases these quantitative methods include:
(a) agglutinin titrations,
(b) phagocytic index determinations,
(c) antitoxin titrations in those diseases in which the pathological effect of infection is intoxication with an
exotoxin,e.g., tetanus.
With bacterial infections in which there is a bacteraemic phase or a migration of the organism through the tissue spaces, the essential defence mechanism is phagocytosis by the polymorphonuclear leucocytes and wandering and fixed histiocytes. The action of protective antibacterial antibody is to coat specifically the antigenic surface of the bacterial cell with globulin, so as to promote the phagocytosis of these bacteria as readily as inert or non-pathogenic bacteria are dealt with by the body. The work of Avery and others on pneumococcal infections has shown that the capsular polysaccharides of the pathogenic Strep. pneumoniae strains exert a negative chemotactic effect upon the polymorpho-nuclear leucocytes, and specific antibody to these polysaccharides reverses this effect. In S. typhi infection of man, the protective antibody is directed against the surface somatic antigens (O and Vi antigens), and antibodies against the flagella antigens are without any protective action. It is usual in the laboratory to titrate serum for antibodies against these specific surface antigens by agglutination reactions, but it must be remembered that, in the body, the action of these antibodies is to promote phagocytosis and consequent destruction of the invading organism. Estimation of the phagocytic index of a serum is a much more accurate method of determining its protective capacity, but it is technically a more difficult test to carry out than the agglutination test.
In summary, then, we can say that most antibacterial immunity is associated with the capacity of the animal's phagocytes to ingest and destroy invading bacteria. In some relatively low grade and chronic infections, such as those caused by Myco. tuberculosis, a hypersensitivity of the tissues to the bacterial antigens develops, and much of the pathology of these infections is related to the inflammatory processes associated with the tissue hypersensitivity.
When we look at virus infections we find a somewhat different situation. Viruses multiply only within susceptible living cells, and before they can gain entry to these cells they must be adsorbed to the cell surface. Protective antibody in virus diseases (known as neutralising antibody) reacts with the virus surface preventing adsorption of the virus to the cell surface. Once a virus has entered a susceptible cell, antibody has no influence on the subsequent multiplication of the virus in that cell. Hence, administration of antiserum to an animal, already showing signs of a virus infection, is quite useless. To be effective the antibody must be given within a short time after the animal was exposed to infection.
Following infection by a virus, neutralising antibody appears in the serum of that animal, and this usually coincides with recovery of the animal from the clinical signs associated with the particular virus infection, provided no permanent damage has occurred to cells or tissues. Hence, by collecting serum samples at the acute phase of a virus infection and another specimen in the convalescent phase some 3-5 weeks later, and titrating these serum samples for neutralising antibody, it is often possible to obtain retrospective serological confirmation of a virus infection.
In many virus infections, antibodies other than neutralising antibody are produced. These are usually detected in a complement fixation reaction, or a gel diffusion precipitin reaction using an extract of an infected tissue as the antigen. Examples of these antibodies are the CF antibody against the group specific soluble antigen in human influenza, and the gel diffusion antibody detected in swine fever and rinderpest infections with extracts of infected pancreas and lymph nodes, respectively. There is not necessarily any correlation between the level of the CF or gel diffusion antibody, and the neutralising antibody. Often CF antibody develops sooner, and disappears sooner, than neutralising antibody.
The new-born mammal is endowed with antibody from its mother. In man, this maternal antibody is transferred across the placenta in utero, while in the bovine it is all absorbed through the gut wall from the colostrum in the first 48 hours of extra-uterine life. In other animals, both placental and colostral antibody are transferred from mother to offspring.
Maternal antibody is passive antibody and has a definite half-life, so that within 6-12 weeks the animal has lost most of its maternal antibody, and must now produce its own immune globulins following contact with appropriate antigens. Passive antibody, when present at a sufficiently high level, protects against infection and can also interfere with, or even prevent, active immunisation of the animal by a vaccine or antigen. Examples of this are the failure to immunise some young children against diphtheria until they are 6-8 months of age, and the necessity to delay immunisation of pups against distemper with attenuated living virus until they are 9-10 weeks of age.
In the dog, maternal antibody is transferred via the placenta as well as the colostrum. Pups one day after birth have serum titres representing about 75% that of their dam's. It has been found that on the average it requires from 6-12 weeks for the level of passive antibody to fall to a sufficiently low level to allow active immunisation of the pup. If, as is usual in the U.S.A., the veterinarian waits until the pups are 9 weeks of age before vaccinating, and the dam had a low antibody titre at the time of whelping, then there will be a period between 6 and 9 weeks after birth when the litter of pups is fully susceptible to distemper.
Vaccines against virus diseases have been successfully developed in a number of instances, and these have been either inactivated vaccines or living vaccines. Examples of an inactivated vaccine are the Salk vaccine used to protect against human poliomyelitis and the so-called crystal violet vaccine used in England to control swine fever. This type of vaccine has only limited value, as we are now learning with regard to poliomyelitis and, in any case, it can only be prepared when methods are available for producing considerable quantities of fully antigenic virus which, when rendered non-infective, will stimulate the production of antibody protecting the animal against the pathological affects of infection by the living virus. Generally speaking this type of vaccine confers a relatively short-lived immunity and does little to cut down the spread of the virus through the animal population.
Living virus vaccines may be of two types. The fully virulent virus may be inoculated into the animal by an artificial route (e.g., variolation), or a combination of virus and specific antiserum may be administered to the animal, resulting in the production of a modified infection which is followed by active immunity to the natural disease in this animal. In either case, a number of virus carriers will be created and the disease thereby will be perpetuated in nature. The other type of virus vaccine is a modified attenuated virus derived by deliberate selection from the wild type virus. These attenuated viruses multiply in the tissues of the animal, producing an active immunity which, in most cases, is similar to that induced by the natural infection, but without producing its severe pathological effects. Great care is needed in producing these attenuated virus vaccines to ensure that they are not contaminated with virulent virus, and that they are sufficiently stable under field conditions so that they will not revert on passage to the fully virulent form. Administration of some vaccines to pregnant animals is not advisable. For example, if bluetongue attenuated live virus vaccine is administered to ewes in the early stages of pregnancy, some lambs will be born with cerebral damage resulting in the "daft lamb syndrome".
In administering a live virus vaccine containing more than one antigenic type, e.g., Sabin type polio vaccine to humans, or bluetongue to sheep, the phenomenon of interference must be considered. When two living viruses are administered to an animal, one of these may suppress completely the multiplication of the other virus even though the two are antigenically unrelated to each other. Multiple doses of vaccine may therefore be necessary for complete coverage of an animal against all the antigenic types of virus, and when there are 16 known antigenic types, as in bluetongue of sheep, this presents some grave practical difficulties. It also accounts for some of the apparent failures and "break through" which are encountered in the vaccine control of virus disease in the field from time to time.
The production of virus vaccines, whether living or non-infectious, has been greatly assisted by the development of tissue culture techniques. Not only has this technique made it possible to produce vast quantities of virus relatively cheaply, but it has opened up the whole field of laboratory investigation of virus diseases. Before any vaccine can be made, the causal agent of the disease must be isolated and studied. It is now possible to isolate many (but not all) of the causal viruses of animal disease without resorting to the often expensive and unsatisfactory technique of animal inoculation. Furthermore, detection of neutralising antibody is relatively easy with those viruses that produce a cytopathogenic effect in tissue cultures.
Perhaps it may not be out of place to mention here some of the principles which should govern the collection of suitable specimens for attempted virus isolation. Care must be taken to prevent cross contamination of the specimens collected. All instruments used at the necropsy should be sterilised by boiling, and a fresh set of instruments used to locate and remove each piece of organ to be examined. Each specimen should be placed in a separate sterile pot which can be securely stoppered. If the specimens have to be sent any distance to the virology laboratory, they should be packed in a thermos flask in wet ice. Wherever possible, it is always more satisfactory to invite the virologist to be present at the necropsy on the animal, and to allow him to direct the collection of suitable specimens for examination. In addition to the specimens for virological examination, a duplicate set of samples should be taken for histological examination. A generous sample of blood should be taken at necropsy (aspirated from the left ventricle of the heart if the animal was dead when first seen by the pathologist) to provide a serum sample which should be stored for subsequent appropriate serological examination.
An interesting modern approach to the vaccination of animals against virus diseases is being investigated in the U.S.A. and elsewhere. It embodies the principle of heterotypic immunity. Virologists have found that various viruses can be grouped together on the basis of morphology and chemical structure. In some cases these viruses have widely different natural hosts. For example, it has been found that the viruses of canine distemper, human measles and bovine rinderpest share many properties in common. Furthermore, it has been found that if a dog is inoculated with human measles virus it does not develop any signs of disease and that antibody to measles virus, but not canine distemper virus, appears in the dog's serum. However, this dog is now fully resistant to challenge inoculation with virulent canine distemper virus and it responds with an accelerated antibody response to this challenge. The interesting aspect of this reaction is that the presence of passive antibody to canine distemper virus in the dog at the time of administration of the measles virus apparently does not interfere with the protection of the dog against distemper by the measles virus.
Similar cross protective reactions have been shown between canine hepatitis virus and the human adenovirus type 4, and between the virus of swine fever and mucosal disease of cattle. This latter reaction is of considerable interest not only overseas, but to us here in Australia. Dr. Baker, of Cornell University, is actively investigating the possible use of mucosal disease virus as a safe and effective method of against swine fever (hog cholera), as part of the U.S.D.A. programme for the eradication of hog cholera from the U.S.A. The concept of heterotypic immunity will continue to be of great scientific interest to us here, and as such it will be investigated intensively, but as far as swine fever is concerned, it is unlikely to be administratively acceptable to those concerned with the control of outbreaks of this disease in the field, or economically acceptable to the swine industry.