Vaccination is the most efficient and effective method of controlling infectious diseases ever developed. The vast improvements in human health through the twentieth century and beyond have been, in large part, a result of the development of effective vaccines. Likewise, many of the improvements in animal health, especially the abundant increases in productivity resulting from effective disease control are a direct result of vaccine use. The eradication of smallpox in humans as well as the elimination of rinderpest in cattle are both directly the result of effective vaccination drives. Various types of veterinary vaccines are discussed below:-
Live attenuated vaccines
The virulence of the pathogen is reduced and immunogenicity is maintained by adapting the pathogen in an unfavourable condition and the organism still replicates. Attenuation is achieved by growing the pathogens in an unnatural host, by passaging in non homologous host (host/cell culture) for repeated period of time (i.e. 70-80 times) or in different physiological conditions or in different environment. Attenuation may also be done by adapting the virus to grow in a temperature lower than the normal called cold adapted virus and the process is called cold adaption. Thermo stable vaccine strain grows at elevated temperature. Temperature sensitive mutants cannot grow at slightly elevated temperature. The process of reducing the virulence and retaining the immunogenicity is called as attenuation so that the pathogen changes its habit of growing.
Advantages
- Replication provides large quantities of immunogen
- There is no need for adjuvant
- Single dose often produce long lasting immunity
- Whole organism has both T and B epitopes
- The vaccine is cost effective and often does not require booster vaccination
- Can be effective against intracellular pathogens
Disadvantages
- Chance of reversion to virulence
- There may be shedding of virus
- Can induce transient immunosuppression
- Cold chain required for transport
- Possible contamination with other animal viruses
- There may be side effects due to unwanted parts of the vaccines
Inactivated/killed vaccine
Inactivated vaccine is prepared by physical or chemical treatment to the pathogen so that the organisms become inactive (loses replication capability) but maintains its immunogenicity. The procedure should not disturb the immunogenic structures or epitopes, but should remove the replication or virulence of the organisms. This vaccine is usually prepared with a virulent strain and the vaccine is more immunogenic. In general these kinds of vaccine are used when attenuated vaccines are not available or for an outbreak where characterization of the organism is not determined and pathogenicity have not been assessed. Examples of chemical inactivating agents are formaldehyde, glutaraldehyde, beta propiolactone etc., they change the structural conformation or cross link the structures and ultimately inactivate the organisms. The physical inactivating agents are gamma irradiation, U-V irradiation etc. which are going to change the structural conformation or cross – linking structures. In general, inactivated vaccine requires an adjuvant to increase the potency of the vaccine.
Advantages
- No possibility of reversion
- No shedding and contamination of environment
- Quite stable, thus less need for cold chain
- More immunogenic
- Whole organism has both T and B epitopes
Disadvantages
- Cannot replicate so antigen is limited
- Require, multiple doses, adjuvants and boosters vaccination
- If not properly inactivated, it may cause disease outbreaks
- Increased risk of allergic reactions due to large amounts of antigen involved
- Costly
- May be ineffective against intracellular organisms.
Toxoid vaccines
Both gram negative and gram-positive bacteria produce exotoxins. Exotoxins can be inactivated by formaldehyde, iodine, other chemical or heat treatment and form toxoid. Toxoid is immunogenic without toxic effects. Toxoid vaccines have been used for tetanus, anthrax etc. Some veterinary vaccines combine both toxoid and killed bacteria by formalinizing whole culture and this is called anaculture. These types of vaccines are available for clostridial diseases. Trypsinization of anaculture makes it more immunogenic.
Advantages and Disadvantages
- Advantage: The exotoxin is immunogenic and whole organism can be avoided.
- Disadvantage: Only effective if diseases caused solely by bacterial exotoxins
Subunit vaccines/conjugate vaccines
It is possible to identify the peptide sites encompassing the major antigenic sites of viral antigens, from which highly purified subunit vaccines can be produced, But increasing purification may lead to loss of immunogenicity, and this may necessitate coupling to an immunogenic carrier protein or adjuvant. Exampleof a purified subunit vaccine is HA vaccines for influenza A and B. Bacterial capsular polysaccharides are immunogenic but incapable of evoking T cell responses. Vaccines efficacy can be greatly increased by conjugating the capsular polysaccharide to a protein carrier capable of supply of T cell epitopes called a conjugate vaccine
Advantages
- Avoids use of whole organism
- Side effects due to undesired part of the organism is reduced
- Supplies multiple epitopes
Disadvantages
- Possible alteration of pathogen protein conformation during purification may decreases immunogenicity
- Can be laboured intensive and costly to purify immunogens
- May require cold chain
- Sometimes too large to fit into the vaccine delivery systems
Peptide vaccines
Once the immunogenic sites of an organism are identified, immunogenic peptides can be synthesized or can be purified from natural sources. Synthetic peptide vaccines would have many advantages. Their antigens are precisely defined and free from unnecessary components which may be associated with side effects. They are stable and relatively cheap to manufacture. Example, foot and mouth disease peptide vaccine where protection was achieved by immunizing animals with a linear sequence of 20 amino acids (141 to 160) of VP1. Synthetic peptides do not readily stimulate T cells and require coupling to a protein carrier which is recognized by T-cells.
Advantages
- Avoids use of whole organism
- Side effects due to undesired part of the organism is reduced
- Small enough to fit into most the antigen delivery vehicles
- Quite stable
Disadvantages
- May be perceived as haptens if not conjugated to carriers
- Rapidly dissipated in tissues, thus requires highly effective adjuvants or effective delivery vehicles.
- May be costly or difficult to identify and purify
Recombinant DNA vaccine
The immune dominant part of a pathogen is cloned into a vector and pathogen DNA is transcribed and translated within the cells of vaccinated animals. Virus proteins have been expressed in bacteria, yeast, mammalian cells, and viruses. E. coli cells were first to be used for this purpose but the expressed proteins were not glycosylated, which was a major drawback since many of the immunogenic proteins of viruses such as the envelope glycoproteins, were glycosylated. An alternative application of recombinant DNA technology is the production of hybrid virus vaccines. Recombinant technology made some useful safe virus vectors for the expression of protective antigens from potentially harmful infectious agents. Compared to the subunit vaccines the vectored vaccines produces good immune responses against various pathogens. Poxviruses, adenoviruses, herpes viruses are commonly used as vectors for vaccines.Examples of vector based recombinant vaccine, ND virus in fowl pox virus, Rabies virus in vaccinia virus etc.
Advantages
- Use of pathogens can be avoided
- Unwanted reaction is reduced
- High immune response.
- Hybrid virus vaccines are stable and stimulate both cellular and humoral immunity.
- They are relatively cheap and simple to produce
Disadvantages
- Replication of vector may induce side effects
- Primary immune responses mounted against vector proteins may generate anti-vector antibodies that blocks booster immunization
DIVA/MARKER VACCINES
Vaccination employing conventional vaccines interferes with the serological detection of infection with the pathogens and thus in the assessment of prevalence and incidence of diseases. This necessitates the development of DIVA vaccines that are capable of distinguishing between antibody responses resulting due to vaccination and infection (DIVA- Differentiating infected from vaccinated individuals) or marker vaccines. A marker vaccine (live or inactivated) is either based on deletion mutant or isolating antigenic proteins that allows the distinction between vaccinated and infected animals on the basis of identifiable differences in antibody responses. A marker vaccine is used in conjuction with a test that detects antibodies against protein that is lacking in the vaccine strain. DIVA vaccine was useful to control avian influenza in Italy.
1Dixit K. Parasana, 2I. H. Kalyani, 3Prashant G. Rathod
1Ph. D. Scholar, 2Professor and Head, Department of Veterinary Microbiology, Veterinary College, Navsari
3Ph. D. Scholar, Department of Veterinary Physiology and Biochemistry, Veterinary College, Navsari