Immunologic response to

Vaccination by I.K.M. Liu

The immune response to vaccination and subsequent protection against disease depend upon several factors, one of which is the sys­tems involved in an immune response. Im­mune responses primarily involve 2 classes of lymphocytes (B- and T-cells), which are respon ible for the production of humoral antibodies and cell-mediated immunity. These systems play significant roles in the host's defense against disease. Neutrophils and macrophages are also involved in immune defense against disease. Through interaction with antigen, an­tibody and complement, phagocytosis and en­zymatic digestion of pathogenic organisms are enhanced.

Serum antibody titers are used as the sole criterion of immunologic protection. Cell-me­diated immunity and neutrophil-macrophage activity are not emphasized nor routinely as­sessed, yet classic studies indicate their impor­tance in immune defense against disease.¹.² Correlation of antibody titer with protection is good; however, cell-mediated function as a measure of protection is equally important. Unfortunately, assessment of cell-mediated immunity and its correlation with protection cannot be performed routinely in horses.

Variations in vaccination programs, popula­tions at risk and products used play major roles in the immune response and subsequent devel­opment of protection. The method by which vaccines are prepared, in general, determines the duration of immunity. Killed-virus vac-ciii^s. generally produce short-lived immunity (6-12 months) and yearly re vaccination pro­grams are required. Modified ilive-virus vac­cines produce, in most cases, a longer duration of immunity and require less frequent revac-cination programs. Most vaccines produced for horses are effective.

Most practitioners assume that once a vac­cine is commercially available, it has met re­quirements for safety, efficacy and immuno-genicity. It is apparent from past experience that such is not the case. A vaccine can only be relied upon to perform reliably through stand­ardization of vaccine requirements by the USDA and strict adherence to these standards by the manufacturers.

The health status of an animal isanother factor that influences the immune response to vaccination. Obviously a diseased horse is less able to respond effectively to antigenic stimu­lation than is a healthy horse.

Antigenic variation among viruses is an im- consideration. As shown in studies in humans major and minor antigenic drifts oc­cur within the influenza virus³ Alterations of amino acid sequences in te protein envelope of influenza virus allow circumvention of any immunity derived from prior exposure or pre­vious immunizations. Evidence indicates mi-

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nor antigenic drifts of the 2 prototypes of equine influenza, as well as antigenic variation with equine herpesvirus-1.^4-7 However, these differences in antigenicity of equine influenza and equine herpesvirus have not warranted changes in virus strains used in vaccines.

Any of the above factors or combination of factors can contribute to the success or failure of protection provided by vaccination. The tar­get of criticism for failures of adequate protec­tion following immunization has been, in many instances, the vaccine. Until valid evidence is found for such criticism, one should carefully evaluate all contributing factors responsible for poor immune response following vaccina­tion. The efficacy of some equine vaccines has been controversial. Clinical evidence on many occasions does not correlate well with experi­mental evidence. As a result, practitioners often improvise and adopt vaccination pro­grams different from those recommended.

Two widespread diseases that result in sig­nificant economic losses to the American equine industry are equine rhinopneumonitis (EHV-1) and equine influenza. Vaccines are available for both diseases.

Equine Rhinopneumonitis

The immune response to EHV-1 vaccine is weak and of short duration (3-4 months). A modified-live-virus vaccine is available for the prevention of respiratory disease caused by EHV-1 in young horses. Experiments have shown that the EHV-1 vaccine prevents equine rhinopneumonitis; however, clinical experi­ence does not support these findings. Attendees at a respiratory disease workshop unani­mously agreed that immunity from vaccina­tion with the modified-live-virus vaccine ofTers some protection but is of short duration.⁸ Vac­cination every 2-3 months was recommended, beginning at 2-3 months until 2 years of age.

Clinical evidence also does not support the manufacturer's claim that the modified-live-vi­rus preparation prevents abortion caused by EHV-1. Although the manufacturers no longer recommend use of the preparation to prevent abortion, many practitioners continue to use the vaccine for this purpose but at more fre­quent intervals (every 2-3 months) than ini­tially recommended.

A killed-virus vaccine is also available. Ex­perimental evidence indicates an adequate im­mune response to vaccination with the killed-virus vaccine if recommended schedules of vac cination are followed. The clinical efficacy of this vaccine cannot be adequately assessed be­cause of its recent introduction to the market.

As previously mentioned, serum antibody ti-ters are considered good indicators of protec­tion against disease. The presence of serum antibody titers clearly indicates exposure to virulent virus and/or to antigens present in vaccines. However, the mere presence of a serum antibody titer does not indicate protec­tion. Therefore, protective serum antibody lev­els must be determined for each disease.

Results of a 2-year study of infection by EHV-1 on a broodmare farm suggested that a serum-neutralizing titer of 1:64 constituted protection against clinical infection.⁹ Another investigator reported that a 1:100 titer consti­tuted protection against EHV-1 infection.¹⁰ The difference between the 2 titers is minimal, however, considering the different types of tests used in each study. The results of these 2 independent investigations indicate that standardization of technics among laboratories should be adopted. Until research methods are standardized, practitioners should consult with their respective laboratories concerning what is considered a protective titer for each disease.

Cell-mediated immune responses to EHV-1 infection have been investigated.^11-13 A recip­rocal relationship between serum-neutralizing titer and cellular immune response occurs af­ter natural infection or vaccination with EHV-1. The clinical significance of this has not been established. Results of investigations deter­mining the importance of cell-mediated im­mune response to protection against the respiratory form of EHV-1 are conflicting. Fur­ther studies are required to establish the role of cell-mediated response in protection against this form of EHV-1 infection. Cell-mediated immunity has been considered to play an im­portant role in preventing transmission of vi­rus from the mare's bloodstream to the fetus in the abortive form of EHV-1 infection.

Immunity produced by natural infection with the respiratory or abortive form of EHV-1 is apparently adequate but of short duration (3-4 months). Mares that have aborted fetuses infected with EHV-1 may abort the following pregnancy from EHV-1 reinfection. Foals that have recovered from an initial EHV-1 infection may be reinfected on re-exposure to the virus 3 months later. However the respiratory infec­tion is less severe, which perhaps indicates a certain degree of immunity.

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Equine Influenza

The immune response produced by vaccina­tion with most equine influenza vaccines pro­vides adequate protection. However, clinical experience and field observations in the US and Europe indicate that protection is short­lived (3-4 months). For this reason, horses at high risk should be vaccinated against equine influenza at 3- to 4-month intervals, particu­larly those horses in training and competition.

Field observations indicate that a hemagglu-tination-inhibition titer of approximately 1:40 or more protects against infection by A-equi-1. Further^observations indicate that horses with serum antibody titers of 1:32 were infected but the disease was clinically inapparent. Experi­mental data are inadequate to confirm a mini­mal protective titer. Suggested minimal protective titers against A-equi-2 infection vary considerably among laboratories because of differences in laboratory technics and meth­odology used. The need for standardization of testing methods and reagents is obvious.

Immunity following experimental infection with A-equi-1 persisted in 2 ponies for 18-24 months.¹⁴ While hemagglutination-inhibition and serum-neutralization titers remained de-tectible up to 24 months (1:33-1:50), comple­ment-fixation titers reached insignificant levels 3-5 months postinfection. Similar results were obtained by other investigators.¹⁵