Types of Vaccines
Vaccines come in several forms, the most common of which are inactivated (killed) or modified live (attenuated). Inactivated vaccines contain relevant components of a disease agent, but they are treated with heat or chemicals to quell their pathogenicity, or disease-producing capacity. Killed pathogen vaccines are fairly easy to manufacture, relatively inexpensive, and won’t cause disease, says Daly. A killed vaccine presents the horse with the inactive proteins (antigens) necessary to generate an antibody response.
The viruses or bacteria in modified live virus vaccines are capable of reproducing in the horse, but their pathogenicity has been reduced and isn’t likely to cause disease. These vaccines stimulate a more pronounced and longer-lasting response to immunization than killed vaccines.
“Although uncommon, there is a risk with some live attenuated vaccines that they could ‘revert’ to virulence to cause disease, particularly in an immune-compromised individual,” says Daly.
The main advantage of using “live” antigens, says Horohov, is that the vaccine better imitates the natural immune-stimulating process to generate an optimal protective immune response. “This is particularly important when a naive (not previously exposed) individual is vaccinated for the first time,” he says. “It is less important for horses with either prior exposure to the disease, or their history includes routine vaccination against that disease. However, we have relatively few live-agent vaccines available for horses.” The most common modified live vaccines are the intranasal equine influenza vaccine and the intranasal strangles vaccine.
Manufacturers also use recombinant technology to produce some equine vaccines. On its website the American Association of Equine Practitioners explains how these are engineered in various ways:
- Live attenuated vector vaccines incorporate pathogenic antigens into a harmless virus or bacteria;
- Chimeric vaccines substitute genes from a pathogen for similar genes in a safe but closely related organism; and
- DNA vaccines consist of a DNA plasmid (a small DNA molecule found in bacteria and other cells) that encodes a viral gene that is then expressed in the horse following immunization.
When a vaccine contains more than one kind of antigen—such as the five-way Eastern and Western encephalomyelitis, tetanus, influenza, and rhinopneumonitis vaccine many veterinarians give in the spring—it’s referred to as a combination vaccine. Horohov and Daly agree that combination vaccines offer convenience and cost savings compared to separating each disease antigen into individual vaccines, given one at a time with multiple sticks and/or veterinary visits. Both list occasions when a single-antigen vaccine might be necessary: when a horse has a history of an adverse reaction to a combination vaccine, for example, or when it is necessary to vaccinate against a specific pathogen due to exposure in an outbreak, such as with equine influenza. Vets also commonly administer vaccines containing just one or a limited number of antigens (e.g., rhino/flu, rabies, Potomac horse fever) to provide comprehensive protection while keeping the horse’s welfare in mind.
Certain diseases develop strategies to evade detection by the immune system, such as through “plasticity” of their genomes, says Horohov. “This is best exemplified by influenza viruses, which use RNA as part of their genome compared to DNA molecules of mammals. Replication of RNA (which is how viruses proliferate once they’ve infected host cells) is much more error-prone compared to DNA(that tends to correct error), leading to a greater likelihood for mistakes or mutations to occur during viral replication.”
“High rates of replication in RNA viruses are like writing out text from a book lots of times very rapidly without the opportunity to correct any mistakes,” Daly explains. “Lots of subtly different virus particles are made during infection of one individual. Over time, the virus (variants circulating in exposed populations) may develop subtle outward differences from virus strains used in vaccines in a process called ‘antigenic drift.’ This eventually means that antibodies raised against the vaccine virus or from a previous infection no longer recognize and neutralize the virus that is circulating in the field.”
Changes in the RNA sequence that alter the virus’ structure might allow it to escape the host’s immune response, adds Horohov. Such mutations are passed on to replicating virus generations and lead to the emergence of new circulating virus strains. When this happens manufacturers must reformulate the target vaccines to include that ‘new’ mutated protein to elicit a host response.
“Fortunately, the equine influenza virus evolves more slowly than human influenza so equine vaccine strains do not need to be updated quite as frequently,” says Daly.
While human influenza vaccines are updated annually, equine influenza vaccines are only updated when the World Organisation for Animal Health (OIE) publishes new recommendations, which occurs infrequently, says Horohov.
You might be aware that your small animals only need to be immunized against certain diseases every three years. “Sufficient evidence has been accumulated for routine vaccination with core vaccines in dogs and cats,” says Daly (which, aside from rabies, are a different set of diseases). While immunizing small animals every three years against certain pathogens appears to provide adequate protection, other agents require annual administration.
“Most (small animal) vaccines have been through extensive trials of monitoring antibody levels over time to determine the interval at which revaccination is required based on how rapidly antibody levels decline and/or how well animals are protected when challenged with the pathogen at different intervals after vaccination,” she continues. “Studies such as these are difficult and costly to perform in horses.”
While corresponding duration of immunity (DOI) data are not available for most equine vaccines, Horohov says that generally the level of antigen-specific antibodies in a horse’s circulation, measured in blood serum as a titer to the agent of interest, tends to decrease fairly rapidly post-vaccination.
“Depending upon the magnitude of the initial antibody response to the vaccine, disappearance of detectable antibodies from the circulation may occur within a year’s time, if not sooner,” he says. “While antibody titers themselves are not always predictive of protection, it is assumed that disappearance of circulating antibodies is a likely sign of increased susceptibility to infection, and this dictates the need to revaccinate or booster frequently, according to manufacturer directions.”
During the initial licensing of a vaccine, manufacturers base their prescribed dosing method and frequency on experimental data they’ve obtained in studies using historical methods to induce immunity and assess protection.
“Typically, this involves administration of an initial priming dose, followed two to four weeks later by a second dose (a booster) of the same vaccine,” Horohov says. “This may be repeated based on other data that show when maximal antibody responses are obtained and a vaccine’s ability to stimulate an antibody response. A few weeks after the last vaccine dose is administered, challenge studies—exposure of the horse to the disease agent—are performed at the time when the expected maximal antibody response occurs. While it would be ideal that antibody titers would correlate with protection—something owners do ask about—this is not always the case.”
Titers Are Not the Answer
The major limitation in using titers to determine if a horse needs immunization has to do with protective immunity’s complex nature, says Horohov. He explains that the immune system responds to antigens in two ways—by producing antibodies (humoral immunity) and attacking antigens that have breached the cells (cellular immunity). When protective immunity involves cellular immunity, antibody titers provide little useful information.
Another reason titers aren’t helpful for measuring protection against diseases has to do with where the immune response must happen in the body to be protective, Horohov adds. A horse is best protected against a respiratory virus such as influenza when the immunization response is localized within the respiratory tract, for instance, which he says is one reason why intranasal vaccines work well.
“While there is some association between antibody titers in the blood and those present in the respiratory tract, it does not correlate well in terms of protection,” he says. “For many infectious diseases, the nature of the protective immune response remains poorly described, making it impossible to define what correlates with protection.”