Chlamydial infections in animals

Chlamydophila abortus

Vaccination

In the U.K., chlamydial abortion in sheep was successfully controlled in the 1960s and 1970s by the use of a single C. abortus strain, formalin-inactivated, egg grown vaccine ( McEwen & Foggie, 1956). This induced an immunity lasting about 3 years (Foggie, 1959) but did not offer complete protection. Disease started to reappear in vaccinated flocks in S.E Scotland in the late 1970s (Linklater & Dyson, 1979), spread to other areas of the country and has continued to increase each year. Leonard et al., 1993 estimated that 8.8% of flocks in Scotland were infected with chlamydial abortion. In 1995, about 1600 flock incidents of chlamydial abortion in ewes were diagnosed in England, Scotland and Wales (Veterinary Investigation Disease Analysis, 2000). It is speculated that more virulent strains of C. abortus have emerged since the 1970s causing a breakdown in vaccine protection. Incorporation of a second abortion strain into the vaccine gave some additional protection, but production difficulties led to withdrawal of this commercial product in the U.K. in 1992 (Jones, 1999).

Experimental studies using inactivated abortion vaccines derived from yolk sac cultivation (Wilsmore et al., 1990) reported protection against challenge with homologous strains and no excretion of live chlamydiae in the faeces. Wilsmore et al., 1984 and Dawson et al., 1986 demonstrated the protective role of delayed-type hypersensitivity in an allergic skin test reaction, which identified vaccinated (i.e. immune) ewes. Other inactivated vaccines have been produced which were found to reduce the level of abortions in sheep challenged with C. abortus (Waldhalm et al., 1982; Hansen et al., 1990; Jones et al., 1995). An inactivated purified chlamydial EB vaccine (Anderson et al., 1990) produced an antibody response predominantly directed against the major outer membrane protein (MOMP) as shown by immunoblotting. Responses to other antigens were less pronounced or inconsistent.

Outbreaks of C. abortus infection have been reported in flocks correctly vaccinated with inactivated vaccine, prompting the evaluation of different inactivation and vaccination methods in a mouse model of infection Caro et al., 2003. Protection was assessed on the basis of clinical signs and the isolation of C. abortus from spleen. Protection was also correlated with the immune response induced by the vaccines, as determined by the production of C. abortus-specific IFN-gamma and IL-4 from splenocyte cultures and the detection of IgG isotypes in serum. BEI was found to be the best C. abortus-inactivation procedure. The inactivated vaccines adjuvanted with QS-21 (QS) or Montanide 773 (M7) induced the best protection both against homologous and heterologous challenge, with an adequate (Th1-like) immune response. These selected vaccines gave good protection in a pregnant mouse model, avoiding uterine C. abortus persistence following delivery.

An alternative approach is to use inactivated subunit vaccines. Good protection was obtained with a detergent extracted, chlamydial outer membrane complex (COMC) vaccine which included MOMP (Tan et al., 1990). However, for C. trachomatis, detergent extracted MOMP has been reported to be a less potent protective immunogen than the conformationally intact molecule (Batteiger et al., 1993).

Later studies have focused on the preparation of recombinant vaccines, which should be easier to prepare and which would avoid the deleterious effects of crude whole chlamydial vaccines. In studies with C. abortus in pregnant sheep, a recombinant protein fragment of MOMP gave some protection, but failed to achieve statistical significance Herring et al., 1998. A major problem here is to deliver the protein in its native form. Another vaccine delivery system, described by Herring et al., 1998, expresses MOMP or MOMP fragments as overcoat proteins on the surface of a filamentous RNA plant virus. However this produced antibody responses in only half the vaccinated mice.

An alternative and successful approach involved the development of a temperature-sensitive attenuated vaccine (Rodolakis & Souriau, 1983). This was achieved by conventional selection procedures rather than by genetic engineering, as no successful systems have yet been devized for the genetic manipulation of chlamydiae. In experimental trials in the U.K., the abortion rate was reduced to about 7% in vaccinated animals compared to 80 % in unvaccinated sheep (Chalmers et al., 1997).

Although vaccination has successfully been used for the reduction of, chlamydial abortion in sheep, this is not the case for cattle. This probably reflects the lesser extent of chlamydial abortion in cattle compared to sheep. Attempts to immunize cattle against C. abortus abortion were carried out using a formalin-inactivated strain, but immunised cows still harboured and excreted chlamydiae (Storz & Kraus 1985). In another attempt to vaccinate cattle, the feline pneumonitis agent [_C. felis_] vaccine was used, but the results were unclear. The commercial C. felis vaccine has not been approved for use in cattle or sheep (Perez-Martinez & Storz, 1985). Moreover, it is unlikely that such a vaccine would be protective as C. abortus and C. felis are antigenically distinct. Hopefully, ongoing genome sequence studies of chlamydiae will lead to the identification or new candidate components for chlamydial vaccines.

[PG] Updated [MEW] July 2003

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