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 and
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 and 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 has been 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
(Herring et al., 1998).
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 and 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). Data are still being collected on how this vaccine performs in the field.
Although vaccination has successfully been used
for the reduction of, chlamydial abortion in sheep, this is not the practice 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 and Krauss, 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 and
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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