Introduction
Live oocysts vaccines
against
coccidiosis in chickens have been used by the poultry industry since
the introduction of CoccivacTM
in 1965 and
ImmucoxTM 20 years
later. Over 3 billion doses
of the 4 brands of vaccines have been sold for chickens. Two of these
vaccines
(CoccivacTM
and ImmucoxTM)
contain oocyst strains originally
isolated from the field while the other two vaccines (ParacoxTM
and LivacoxTM) use
some or all attenuated or
precocious strains of coccidia. All of these vaccines induce protective
immunity to coccidial infection.
The vaccines have been
successful for breeder flocks, and over the last
few years there is a steady increase in use for commercial
broilers
and roasters. Recent reviews on the immune response of
chickens to coccidial
infection and immunization allows for a more complete discussion on how
live oocyst vaccines function.
Coccidial
life cycle
There are 7 different
species of
coccidia (genus Eimeria) commonly found in the
intestinal tract of the chicken and each infects specific areas of the
gut. Except for the infective oocyst stage, which is shed in
feces onto the
litter, the remainder of the coccidial life cycle takes place in the
intestinal tract. Sporulated oocysts are ingested by the bird. These
release the invasive sporozoite stages that penetrate the gut cells to
initiate development of asexual intracellular schizonts. The schizonts
produce large
numbers of a second invasive stage, termed the merozoite, which
penetrates other gut cells to produce a further generation of schizonts.
The number of asexual
generations
varies from 2 to 4 depending on the species of coccidia. Asexual
multiplication results in an exponential increase in parasite
numbers. Ultimately we see the intracellular macro and micro-
gametocyte stages of the life cycle give rise to macro and
microgametes, which fuse to form a zygote. This stage develops into an
immature oocyst, which is shed onto the litter. The Eimeria lifecycle
is extremely efficient with the potential to produce 300,000 oocysts
following infection of the susceptible chicken with a single sporulated
oocyst.
Role
of immune response
The complex
life cycle stimulates a number of
immunological responses, which will vary in anticoccidial effect. The
response comprises both nonspecific and specific responses by the
immune system. These have evolved in the intestine to respond against
invasive viral, bacterial and parasitic pathogens. Extra and
intracellular developmental stages of coccidia will stimulate both
humoral and cellular immuno-logical responses with an initial or
primary infection in addition to subsequent secondary reinfection. The
immune response is specific to each of the 7 chicken coccidial species.
Immunovariability
between
strains
of the same species of coccidia occurs, which may result in a
corresponding lack of cross protection. It is possible to protect
flocks against one species or strain of coccidia.Complete or partial
susceptibility may persist with infection by another species or variant
strain of the same species of Eimeria. Humoral
responses in the form of serum antibody and local intestinal
mucosal antibody produced by mucin and B lymphocytes are a direct
result of the interaction between macrophages and other
antigen-presenting cells and the invading sporozoite and merzoite
stages of the Eimeria lifecycle. This response,
derived from complex interactions
between macrophages,
lympho-cytes, dendritic and epithelial cells, represents the first line
of defense to any invasive organism in the intestine. Although highly
effective against bacterial colonization and viral infection, the
humoral response to coccidial infection is limited in scope. It may play some role with the
early phase of parasite infection or the later sexual stages of
development. Cell mediated immune response that has the major role in
inhibition coccidial infection and development of intracellular
parasites. Cell mediated immune response to coccidial infection
represents a complex
interaction of the parasite with gut associated
immune function.
A thorough understanding of
this
process requires the identification of various T lymphocyte
populations, characterization of the function of macrophage,
dendritic and natural kill (NK) cells, and elucidation of cytokine and
lymphokine immune response regulation. Investigations in these
areas are still incomplete for avian coccidia,
but comparisons between studies on coccidiosis in chickens and the
results from other parasitic infection models in mice now provide a
better understanding on the complicated process of anticoccidial cell
mediated immunity (CMI).
Antigen-specific and
non-specific activation of T
lymphocytes, NK cells and macrophages are necessary components of this
CMI process. There is strong evidence the intraepithelial T lymphocytes
with surface pheno-types positive for CD8+, mediate host immunity to
coccidial parasites. Sporozoites
occur within the CD8+ lymphocytes
during primary coccidial infection, which indicates that these cells
may be involved in transport of sporozoites within the gut.
Increased numbers of the T cells sometimes appear as early as 8 days
post infection in the epithelium of the gut following secondary
coccidial
infections.
They are also seen in direct contact with infected epithelial gut
cells. This suggests that the CD8+cells are cytotoxic in nature and may
destroy the infected host cells.
Further confirmation of the
importance of CD8+ T cells in cellular
response to coccidial infection is seen in studies that deplete the
CD8+ cells by treatment of
anti-CD8+ mono-clonal antibody. More oocysts
are produced during primary infection in birds subjected to anti-CD8+
treatment than were measured in untreated and infected
controls. This treatment before secondary
infections completely abolished
resistance to this challenge infection.
The NK cells seem to play
an important role in local early defense of
coccidial infection, while macrophages may be more important in
phagocytosis of the sporozoite stages. Both types of cells are known
secretors of cytokines during and after
coccidial infection. Observations of chicken intestinal
intra-epithelial lymphocytes (IIEL) have shown that the associated NK
cells mediate spontaneous cytotoxicity. These cells are found in
the greatest numbers in the early stages of
coccidial infection, suggesting a possible role in control of parasite
proliferation. In addition, levels of NK cell activity in the
intraepithelium, increased in infected animals and coincided with
parasite elimination. This indicates that the IEL
NK cells may be involved in blocking
invasion of the gut by sporozoites. Growing evidence on cytokines and
lymphokines produced during coccidial infection and immunization
suggest that these are the important molecules in controlling host CMI
responses. Tumor necrosis factor-a (TNF-a) is secreted by NK cells and
macrophages
and has been shown to exert a protective effect in coccidial
infections. Interferon-gamma (JFN-y) is
believed to play a critical role in
protection of chickens against coccidia infection as evidenced by
increased bird weight gains, decreased oocyst production and inhibition
of intracellular parasite development of IFN-y tented birds.
Exactly how WN-y regulates
anticoccidial activity is not known, but the
fact is that this cytokine activates macrophages, NK cells and
cytotoxic T lymphocytes ruakes it an important participant in CMI
anticoccidial protection.
Live
oocyst vaccines
Live
oocysts vaccines
direct the
immunological response of the chicken by stimulating the immune system
towards protection against specific coccidial infection. Antigen
presenting cells (macrophages and dendritic cells) combined with NK
cells, T-cell-secreted cytokines (IFN-y and TNF) and CD8+ cells are
needed to produce response against coccidial reinfection.
Based
on the known role of the immune response of the chicken to
coccidiosis, it is likely that Th- 1 rather than Th-2 cell biased
response occurs. This requires that low (and not high) levels of a
primary parasite infection should be given to flocks to initiate the
cascade of events to produce Th-l cells. The secretion of IFN-y, TNF
and possibly other cytokines would then act through host receptors to
limit coccidial development. Although a direct role of CD8+
cells in CMI response for resistance to coccidiosis is still unproven,
the presence of significantly higher numbers of CD8+ IL near
parasitized cells in immunized birds further suggests that soluble
cytokines combined with cytotoxic T cells are involved in the
protective CMI response to
coccidiosis. Correspondingly,
higher
levels of
parasite invasions such as those observed with drug resistant
infections in laboratory and field studies appear to induce a Th-2 cell
response (Figure 2), which would not establish protection in the birds.
Invasions by large numbers of coccidial parasites would mimic bacterial
or viral infection and thereby drive the gut-associated lymphoid tissue
immune system toward a B cell type response. This may in part explain
why treatment for coccidiosis after heavy infection with drug-resistant
field strains of Eimeria must be repeated more
than once to control infection.
The
recent findings that IL-4, IL5 and IL-6 deficient birds actually
produce lower numbers of parasite stages than the cytokine-intact
infected controls lend further credence to inhibition of immune
coccidial protection by the Th-2
biased response. It is therefore imperative to ensure levels of primary
oocyst exposure
to insure that the correct immune response is
elicited. Immunization
with live vaccines is therefore completely different from
field infections involving high levels of parasite infection. This
makes a live coccidiosis vaccine more desirable because the birds are
programmed to produce the protective response
before they are exposed
to field challenge.
Published
in
Zootechnica
International, June 1999
