Strangles Vaccines and Immunity to Streptococcus equi

Equine strangles is caused by Streptococcus equi, a biovar, or clonal descendent of an ancestral S. zooepidemicus. Recovery from the disease is accompanied by onset of acquired resistance to the disease in approximately 75% of horses, an immunity that persists for 5 years or longer — hence the greater incidence of strangles in younger horses.

The immunologic basis of acquired resistance is not well understood but appears to function at the level of the tonsil-resistant horses that exhibit rapid tonsillar clearance of S. equi following experimental intranasal challenge. Although most horses are colonized by the closely related S. zooepidemicus, which shares many cross reactive immunogenic proteins with the clonal S. equi, these horses are not protected against strangles. Conversely, strangles vaccines do not protect against respiratory or uterine disease caused by S. zooepidemicus. Thus, current vaccine research is heavily focused on immunogens expressed by S. equi but not by S. zooepidemicus.

Vaccination was first attempted over 100 years ago with a variety of live and killed preparations of S. equi. Studies in Australia in the early 1940s indicated that useful protection could be stimulated using formalinized suspensions of gently-heat-inactivated, early-growth-phase bacteria. A similar vaccine marketed in the United States in the 1960s was associated with a high frequency of local and systemic reactions and later replaced by vaccines prepared from protein-rich acid and enzyme extracts. These modifications resulted in fewer adverse reactions and stimulation of high levels of serum antibody to the antiphagocytic SeM protein.

However, although potent, their use in the field provided only marginal levels of protection. Since injected vaccines failed to induce the local mucosal immune responses that develop in convalescent protected animals, a non-encapsulated, attenuated S. equi was developed as an intranasal vaccine. A modification of this concept involving the injection of a live aroA– mutant of S. equi into the upper lip has been marketed in Europe. These live vaccines have the potential to cause abscesses following inadvertent entry into needle puncture sites. Other safety concerns include reversion to virulence and the occasional occurrence of purpura hemorrhagica and bastard strangles. Moreover, not all vaccinates make protective responses, which may indicate faulty administration or a non-responder horse.

Vaccines in Current Use

Acid and enzymatic extract vaccines (USA, Australia): Naïve horses and foals require a schedule of 2 or 3 doses at an interval of 2 weeks. Booster doses may be given once annually. Mares boostered a month before foaling will have enhanced levels of colostral antibody. Animals with titers of 1:1600 or greater in the SeM ELISA should not be vaccinated because of the risk of purpura and because this level of antibody may signify an existing protected state. Also, horses known to have had strangles within the previous year need not be vaccinated.

Intranasal vaccine (USA): Only healthy, nonfebrile animals free of nasal discharges should be vaccinated. Two doses are given at a 2 to 3 week interval and must be applied so that the vaccine reaches the naso and oropharyngeal tonsillar tissues. Foals may be vaccinated at 1 to 2 months of age, although there is an enhanced risk of mandibular abscessation in this age group. Use of live vaccine during an outbreak is controversial and perhaps should be restricted to animals with no exposure to known cases or exposed animals. It should be kept in mind that protective immunity will not develop until at least 2 weeks after vaccination and that the process of vaccination itself increases the risk of transmission of wild virulent S. equi should an infected horse unknowingly be handled during the procedure. However, numerous anecdotal experiences suggest that use of intranasal vaccination during an outbreak has been effective in stopping an outbreak.

Mucosal vaccine (Europe): The vaccine is injected submucosally on the inside of the upper lip in a dose volume of 0.2 ml. Horses older than 4 months are vaccinated twice at an interval of 4 weeks to prime and subsequently every 3 months to maintain immunity. If continuous immunity is not required, a single dose will restore immunity in a primed horse at risk of exposure to S. equi.

Safety and efficacy issues are driving efforts to develop improved strangles vaccines in a number of laboratories around the world. Comparisons of the genomic sequences of S. equi and S. zooepidemicus have the potential to greatly accelerate discovery of vaccine components. However, since strangles is a disease with a complex pathogenesis involving several virulence factors that operate at different stages of infection, discovery of an effective combination of protective antigens and appropriate mode of delivery and presentation will require expensive and time-consuming experimentation in the natural host.