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Review Article
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Trends and Advances in Vaccines Against Protozoan Parasites of Veterinary Importance: A Review |
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A.K. Singh,
A.K. Verma,
Neha ,
Ruchi Tiwari ,
K. Karthik ,
Kuldeep Dhama
and
S.V. Singh
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ABSTRACT
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By 2050 to feed the estimated human population of around 9
billion, there is requirement of 50% increase the food production, which can
only be fulfilled by clean, healthy and sustainable food animal production.
Livestock industry is facing considerable economic losses due to infectious
diseases. So an effective control strategy is need of today to control these
infectious diseases and contribute in augmentation of livestock production.
Parasitic diseases have a major impact on livestock production, reproduction
and hence economy. Protozoan parasites are major causes of human and animal
disease causing extensive morbidity and mortality, particularly parasitic disease
in tropical and sub-tropical climatic regions. Many protozoal parasitic diseases
are zoonotic. Limiting the impact of parasitism in both man and livestock relies
almost exclusively on the use of antiparasitic drugs. Development of resistance
towards chemotherapeutic agents has forced the scientist to discover some alternative
for control of parasitic diseases. Recent advances in immunology and biotechnology
have sensitized the scientists or researchers to develop the newer and safer
vaccines for control of parasitic diseases. This review is intended to provide
state-of-art information to the reader with an overview on the trends, advances
and perspectives in vaccines and vaccinology against important parasitic diseases
of livestock and poultry viz., coccidiosis, anaplasmosis, giardiosis, babesiosis,
Neospora infection, toxoplasmosis, theleriosis, sarcocyst infestation,
leishmaniasis, trypanosomiasis and trichomoniasis, which altogether play crucial
role in the prevention of protozoan parasitic diseases of animals.
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Received: October 08, 2013;
Accepted: October 31, 2013;
Published: January 11, 2014
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INTRODUCTION
According to an estimate, by 2050 to feed the estimated human population of
around 9 billion, there is requirement of 50% increase the food production.
This requirement can only be fulfilled by clean, healthy and sustainable food
animal production (Mahima et al., 2012a; Fitzpatrick,
2013). In modern days, the livestock industry is facing considerable economic
losses due to infectious diseases of viral, bacterial, fungal, parasitic origin
(Rogers and Randolph, 2006; Jones
et al., 2008; Cascio et al., 2011;
Verma et al., 2008, 2012a,
b; Kumar et al., 2011;
Dhama et al., 2013a, b).
So an effective control strategy is need of today to control these infectious
diseases and contribute in augmentation of livestock production (Innes
et al., 2011; Dhama et al., 2013c,
d). In past or till now, the limiting of impact of
parasitism relies on use of chemotherapy like anthelminthic, antiprotozoal drugs
etc (Vercruysse et al., 2004). Due to development
of resistance towards these chemotherapeutic agents, scientists or researchers
are now thinking towards the prevention of parasitic diseases through use of
vaccines (Barriga, 1994; Vercruysse
et al., 2004; Stern and Markel, 2005; Innes
and Vermeulen, 2006; Paul-Pierre, 2009; Knox,
2010; Sharman et al., 2010; Liu
et al., 2012; Dhama et al., 2008,
2013e). All these facts have forced the researchers
to develop some alternatives for prevention and control measures like effective
vaccination, immunomodulators and novel therapeutic regimens (Meeusen
et al., 2007; Vercruysse et al., 2007;
Manzano-Roman et al., 2012; Dhama
et al., 2013d; Jacob et al., 2013;
Mahima et al., 2012b). Effective ways to combat
parasites are very limited due to their complex nature and complicated relationship
with the hosts. Vaccine is a substance used to stimulate the production of antibodies
and provide immunity against one or more diseases. It is prepared from causative
agent of disease, its products, treated to act as antigen without causing disease
(Stern and Markel, 2005). With the development of immunology,
a continuous flow of vaccines to the market is going on, but among them the
percentage of parasitic vaccine is very low (Vercruysse
et al., 2004). The development of vaccines against the parasitic
diseases for domestic animals is most fascinating, promising and challenging
field (Innes and Vermeulen, 2006). Majority of the
problems are due to their complex life cycle and difficulty in their in vitro
culture (Cornelissen and Schetters, 1996).
Parasitic diseases have a major impact on livestock production worldwide with
infection arising from a range of helminth, protozoan and ecto-parasites and
out of these, many parasitic diseases are zoonotic (Innes
and Vermeulen, 2006; Cornelissen and Schetters, 1996;
Paul-Pierre, 2009; Dhama et
al., 2013a, b, c, f;
Reichel et al., 2013). This review is intended
to provide state-of-art information to the reader with an overview of vaccines
available against parasitic diseases of livestock viz., coccidiosis, anaplasmosis,
giardiosis, babesiosis, Neospora infection, toxoplasmosis, theleriosis,
sarcocyst infestation, leishmaniasis, trypanosomiasis and trichomoniasis, which
are very useful for prevention and control of parasitic diseases in animals.
PROTOZOAN DISEASES
Protozoa are unicellular, eukaryotic, microscopic organisms, belongs to subkingdom
protozoa, having a distinct nucleus as well as endoplasmic reticulum, golgi
apparatus, mitochondria in the cytoplasm. About 65,000 species of protozoa have
so far been named of which a great majority are free-living, while only 7000
protozoan species are parasitic both in vertebrate and invertebrate animals
(Levine, 1985).
Metazoan and protozoan parasites are one of the major causes of disease causing
extensive morbidity and mortality in animals (Knox, 2010).
These parasites are major impediment to the introduction of high-productivity
breeds in poorer or developing countries. Among these many of the parasites
are zoonotic in nature that also increases their economic importance. At present,
no vaccine for human protozoal disease is available; however, several veterinary
vaccines are available in the market (Meeusen et al.,
2007; Vercruysse et al., 2007). Among vaccines
against protozoan diseases of livestock, many are based on live organisms, but
recently there is progress in development and commercialization of killed subunit
vaccines (Lightowlers, 1994; Sharman
et al., 2010).
ANTIPROTOZOAN DRUGS- PROBLEMS IN THE NEAR FUTURE
Drugs against protozoan parasites are widely used to prevent the infection
but protozoans are able to develop resistance against these drugs, which is
a serious problem in human and veterinary (Vercruysse et
al., 2007). Broiler industry is facing the crisis of antiprotozoan drug
resistance against the common coccidiostats used in the farm (Stephan
et al., 1997). This has lead to the shuttling of drugs used against
Eimeria so as to keep resistance development under check. Resistances
against antiprotozoan drugs are now reported in Trypanasoma (Geerts
et al., 2001) and also in canine Babesiosis (Collett,
2000). Extreme use of antiprotozoan drugs has not only lead to the resistance
against these drugs but also the residues in the animal products enter the food
chain causing cross transfer of resistance (De Ruyck et
al., 2000; Geary, 2002). Apart from these problems
these drugs can also enter environment from the secretions and excretions of
the animals, threatening the public further (Steel and Wardhaugh,
2002). Hence the current regime for the treatment several protozoan infections
are not proper and the search for new antiprotozoan drugs has not yielded a
fruitful result (Von Samson-Himmelstjerna and Blackhall,
2005). To solve these problems vaccination will be a good means to control
the disease.
VACCINE AND ITS TYPES
Vaccines are dead or inactivated organisms or purified products derived from
them. There are several types of vaccines in use (Table 1):
• |
Killed or inactivated |
• |
Live attenuated |
• |
Subunit |
• |
DNA Vaccine |
• |
Edible vaccine |
Killed or inactivated: It is produced by killing the etiological agents
of disease either by chemical (formaldehyde or beta-propiolactone)/heat/radiation
and such vaccines are more safe and stable than live vaccines.
Table 1: |
Types of protozoan vaccines |
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These are inactivated vaccines and easy to prepare. In this type of vaccine,
the replicative function of etiological agent should be destroyed, while the
outer coat of agent should be left intact. For its effectiveness, large amount
of antigen is required in comparison to live vaccine. Excessive treatment can
destroy immunogenicity whereas insufficient treatment can leave infectious agent
capable of causing disease. The commercially available killed/subunit vaccines
available against protozoan parasites are given in Table 2.
Advantages:
• |
Killed vaccines are stable |
• |
Constituents clearly defined |
• |
Unable to cause the infection |
Disadvantages:
• |
Need several dosages |
• |
Local reaction common |
• |
Short lasting immunity (Shkap et al., 2007) |
Live attenuated: Live vaccines are prepared from attenuated strains
that are almost or completely devoid of pathogenicity but having the immunogenicity
therefore they are capable of inducing a protective immune response. They multiply
in the host and provide continuous antigenic stimulation over a period of time.
The commercially available live protozoal vaccine against animal diseases is
given in Table 2.
Advantages:
Disadvantages:
• |
It required refrigeration |
• |
Contraindicated in immunosupressed patient |
• |
Poor stability |
Subunit vaccine: Instead of entire microbe, subunit vaccines include
only that best antigen which stimulates the immune system. It contains only
the essential antigens and not all the other molecules that make up of microbe.
It is of three types: (a) Natural tissue purified protein, (b) Recombinant protein
antigens and (c) Chemical small peptide vaccines. Two subunit vaccines are available
in market for canine babesiosis caused by B. canis. These vaccines contain
soluble antigens from the pathogen of canine babesiosis.
Table 2: |
Progress in protozoan vaccines and their commercial availability |
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NobivacPiro® is a newly marketed vaccine which contains soluble
protein antigen of two pathogens namely B. canis and Babesia rossi
that broadens the immunity. ABIC Veterinary Products, Israel markets a novel
killed subunit vaccine for poultry coccidiosis (Wallach,
1997). The peculiarity of this vaccine is that it targets macrogametocyte
stages of coccidia which results in formation of oocyst unlike live vaccines
which target merozoite stages. Laying hens are immunized by this vaccine rather
than chicks, transferring immunoglobulins to the yolk which is the added advantage
of this vaccine (Wallach et al., 1995). A subunit
vaccine comprising of antigens such as Gam82 and others purified from the Eimeria
gametocytes has been reported to be safer and effective in preventing coccidiosis
in birds (Vermeulen, 1998; Wallach
et al., 2008; Jang et al., 2010).
Advantage:
• |
Low adverse reactions |
• |
Not infectious, so they can safely be given to immuno-suppressed animals |
Disadvantage:
• |
As native structure of antigens is difficult to retain, so
antibodies produced after immunization may not recognize the same protein
on the pathogen surface |
• |
Do not stimulate immune system properly and requires boosters to have
good immune response (Ingolotti et al., 2010) |
DNA vaccines: These vaccines are the third generation vaccines, in which
DNA responsible for particular protein is directly injected into host to produce
the desired immune response. At present this technology is proving helpful in
control of protozoan infections (Dumonteil, 2007; Liu
et al., 2006). DNA vaccines are developed for a handful of protozoan
infections of animals and their studies on laboratory animals showed good results
that these vaccines can be adopted for animals (Dadara
and Harn, 2005; Dhama et al., 2008; Carvalho
et al., 2010; Kumaragurubaran and Kaliaperumal,
2013).
DNA vaccine for Toxoplasma gondi targeting the bradyzoite stage antigens
BAG1 and MAG1 reduced cyst burden in mice when challenged with infection (Nielsen
et al., 2006). Recombinant plasmid using T. gondii surface
antigen 1 (SAG1) and 14-3-3 protein has been found to induce protective immunity
in BALB/c mice (Meng et al., 2012). Recently,
a DNA vaccine expressing eukaryotic translation initiation factor (eIF4A) protein
of T. gondii has been reported to be promising in inducing protective
immunity against acute toxoplasmosis in mice (Chen et
al., 2013). Development of DNA vaccines has been tried against protozoan
parasites, Leishmania and Trypanosoma cruzi also which affects human
being. Leishmaniasis, a major public health zoonoses, is a complex disease caused
by at least 18 species of genus Leishmania transmitted by hematophagous sandflies
while T. cruzi is the causative agent of Chagas disease. Cross-protection
studies showed that infection by one species of Leishmania may or may not protect
from subsequent infection by another species of same genera (Xu
and Liew, 1994, 1995). In dogs, therapeutic DNA
vaccine has also been developed against Trypanosoma cruzi infection (Quijano-Hernandez
et al., 2008). Another DNA vaccine targeting the Leishmania infantum
acidic ribosomal protein P0 (LiPO), Leishmania major DNA vaccine
encoding PSA-2 antigen, Cysteine Proteinase (CP) a and b DNA vaccines also had
good immune response studies in mice (Dondji et al.,
2005). Another DNA vaccine encoding L. donovani nucleoside hydrolase
NH36 is therapeutically active against murine visceral leishmaniasis produced
by L. chagasi (Handman et al., 2000;
Aguilar-Be et al., 2005; Gamboa-Leon
et al., 2006). Nucleoside hydrolase DNA vaccine (Leishmune®s)
has been found effective for immunotherapy of canine visceral leishmaniasis
(Borja-Cabrera et al., 2012). DNA vaccine for
Anaplasma mariginale targeting the major surface protein namely MSP1b
yielded good antibody response and fair protection was noticed in challenge
studies in cattle (De Andrade et al., 2004).
Development of DNA vaccine targeting babesiosis disease in canines has been
attempted with protein p50 gene coding the Babesia canis, which generated
protective immunity, while the p36/LACK antigen gene and L. major GP63
antigen encoding gene inducing Th1 immune response has been utilized for Leishmaniosis
(Walker et al., 1998; Fukumoto
et al., 2007). DNA vaccines have also been developed against coccidiosis
in birds, employing the 3-1E and EtMIC2 genes (Min et
al., 2001; Ding et al., 2005).
Advantages:
• |
Safe as do not contain any form of pathogen |
• |
No risk of infection |
• |
Administration is easy by either I/M or I/D routes |
• |
Manufacture of multivalent vaccines by combining multiple DNA |
• |
Stability of the vaccine for storage and shipping especially in tropical
zones |
• |
As compared to live attenuated or recombinant vaccines DNA vaccines are
more stable |
• |
Cost effective, hence ideally affordable |
• |
Produces both humoral and cellular immune response |
• |
Unlike live attenuated vaccine there is no risk of reversion to virulence |
Disadvantages:
• |
Risk of effective genes controlling cell growth |
• |
Possibility of including antibody production against DNA |
• |
Chance of inducing mutation |
• |
Complexity in vaccine formulation |
• |
Plasmid may get integrated into the cell and can lead to transfer of resistance
gene (Kumaragurubaran and Kaliaperumal, 2013) |
Edible vaccine: Recent advances in sciences has made it possible that
vaccine can be administered orally as edible vaccines hence eliminating the
problem of pain which is associated with the needle pricks during vaccination
(Dhama et al., 2013e). Though the concept of
producing edible vaccine started in 1990s but it had rapid strides and
all sorts of plants are being exploited in the recent years so as to get good
expression of the required gene of interest so that good immunity may be elicited
against a particular organism (Curtiss and Cardineau, 1990).
Edible vaccine which enters orally released in the intestinal tract elicits
both humoral and mucosal immunity. More work has been carried out the malarian
parasite which of importance in human aspect (Clemente and
Corigliano, 2012). Tomato has been used as an expression plant so that it
can be easily consumed by human (Chowdhury and Bagasra,
2007). In livestock sector edible vaccines has been developed against coccidiosis
in poultry which is an important disease in poultry industry, caused by Eimeria
tenella. Microneme protein EtMIC2 of this deadly pathogen was expressed
in tobacco leaves (Sathish et al., 2011). Feeding
trails of this tobacco leaves with the microneme protein resulted in good antibody
synthesis and there was low oocyst shed down in the droppings. The combination
of EtMIC2 and EtMIC1 yielded good antibody response along with increase in weight
gain (Sathish et al., 2012).
Advantages:
• |
Plant cell wall act as a barrier protecting the antigen of
interest to reach the target place safely (Streatfield,
2006; Hayden et al., 2012) |
• |
Plants contain some phytochemicals which act with co-ordination with the
antigen so that it provides good immune response even in the absence of
adjuvants (Pasquevich et al., 2011) |
• |
Secondary plant metabolites like lectins, saponins, alkaloids, phenolic
compounds and flavonoids act as an immune stimulant (Kostrzak
et al., 2009) |
• |
Edible vaccines are free from bacteria, fungi and viruses because plant
pathogens are not deleterious to animals |
• |
Needle prick is eliminated and hence there is no pain and no damage to
muscles |
• |
As the administration of oral vaccine is much easier than injection, it
can be applied for mass vaccine and time can be saved |
• |
Production can be done in large scale with available plants locally and
can be stored for longer period (Dhama et al.,
2013e) |
Disadvantages:
• |
Negative impact on public because of the use of edible plants
for production of vaccine |
• |
Possibility of inducing oral tolerance and side effects like allergy |
• |
To produce highly expressive plants it needs time and patience (Jacob
et al., 2013) |
VACCINES AVAILABLE AGAINST SOME OF THE PROTOZOAN PARASITES
Vaccines against coccidia
Coccivac®-B: It is a live, sporulated oocyst vaccine produced
from isolates that were collected in the late 1940's, before the current anticoccidial
products were introduced. This vaccine is prepared from anticoccidial-sensitive
strains of Eimeria acervulina, E. mivati, E. maxima and
E. tenella, unlike present-day field oocysts, these isolates had never
been subjected to selection pressure by anticoccidials resulting in resistance.
Coccivac-B vaccine is a valuable tool to restore the performance of existing
anticoccidials (Chapman, 1994). In experimental study
on birds, this vaccine produced variable degrees of protection with the five
different strains of E. tenella (Awad et al.,
2013).
Coccivac®-D: It is a live, sporulated oocyst vaccine
containing different species of Eimeria viz., Eimeria acervulina,
E. maxima, E. necatrix, E. hagani, E. praecox, E.
tenella, E. brunetti and E. mivati. To induce complete immunity,
the original dose of coccidial oocysts must complete at least four life cycles
in the flock (Johnson and Reid, 1970).
Coccivac®-T: It is a live coccidiosis vaccine containing
sporulated oocysts of Eimeria dispersa, E. meleagrimitis, E.
adenoides and E. gallopavonis that is administered to day old turkey
poults via spray cabinet. The strains of Eimeria in Coccivac-T were isolated
prior to common use of modern ionophore and chemical anticoccidial products
and are highly sensitive to all in-feed anticoccidials (Mathis
and McDougald, 1989).
Nobilis® COXATM: This vaccine is a live vaccine having
a special property of being active even in presence of ionophore compounds.
The vaccine contains strains of E. acervulina, E. tenella and E. maxima which
are tolerant to ionophore compound. The benefit of this vaccine is that apart
from production of immunity the vaccine allows the use of ionophore compounds
during the 3-4 weeks of age when the immunity is poorly developed (Vermeulen
et al., 2001).
Eimeriavax -4 m: This vaccine contains viable oocysts of Eimeria
acervulina Strain RA, E. maxima Strain MCK+10, E. necatrix
Strain mednec3+8 and E. tenella Strain Rt3+15 suspended
in phosphate buffered saline (PBS). Each dose comprises a minimum of E.
acervulina 50 oocysts, E. maxima 100 oocysts, E. necatrix
100 oocysts and E. tenella 150 oocysts, with a minimum predicted titre
of 1.6x104 oocysts mL-1 at the end of the shelf-life
(Gore et al., 1983). The advantages of Eimeria
vax 4 m are:
• |
Simple, single dose, eye-drop or oral application |
• |
Safe in chickens from day-old |
• |
Immunity induced within 10 days against the four major species of Eimeria
(E. acervulina, E. maxima, E. necatrix and E. tenella) |
• |
Effective in broiler breeders, broilers, free range and layer flocks |
• |
Supplied ready to use |
• |
Anticoccidial medications are not required |
• |
Provides productivity improvements (McDonald and Shirley,
2009) |
Immucox: Oral coccidiosis vaccine of live oocysts of Eimeria
spp. designed to help healthy Chicken Broilers and Roasters to develop immunity
to coccidiosis. This is a one-time vaccination that delivers protective immunity
through the productive life of the bird. It is a vaccine approved for water
or gel delivery in the hatchery (Lee, 2006).
Paracox®-8: It is a live attenuated oral vaccine consisting
of translucent, suspension of oocysts derived from eight precocious lines of
coccidian, used for the active immunization of chickens against different Eimeria
spp. viz., Eimeria acervulina, E. tenella, E. brunetti,
E. mitis, E. necatrix, E. praecox and E. maxima
(Shirley et al., 2005). The dose of vaccine
is 0.1 mL per chicken, which can be administered orally either by spray on feed
or in drinking water or by hatchery spray.
Livacox: It is live attenuated coccidiosis vaccines for domestic poultry
(Gallus domesticus). Its range consists of LIVACOX® T
for broilers and LIVACOX® Q for breeder and layer pullets (Shirley
and Bedrnik, 1997).
CoxAbic: It is first commercially available subunit vaccine for poultry
and contains purified antigens isolated from the macrogametocyte (sexual stage)
of Eimeria maxima (Belli et al., 2004).
Vaccination using gametocyte antigen through the breast muscle will guide to
production of antibody response (Sharman et al.,
2010).
Vaccines for anaplasma
Anaplaz: It is the first anaplasmosis vaccine manufactured for cattle in
the United States by Fort Dodge. More recently, Mallinkrodt (later Schering-Plough)
marketed a vaccine called Plazvax®. Both of these vaccines protect against
Anaplasmosis by similar mechanisms. The vaccines contain killed Anaplasma
marginale, harvested from infected cattle (Brock et
al., 1964). The vaccines do not prevent the animal against infection
by the Anaplasma organism, but protect the animal from development of
clinical disease. They are "immune carriers. That is to say, they are
"immune" to becoming sick from the agent but are carriers of the agent. Dose
rate of 1 mL by sec cycle-1 route and repeated after 3-4 week and
revaccinate annually by single dose, 1 mL.
Anavac: It is a modified live vaccine, which is safe and effective when
given to young cattle. They become infected with the vaccine strain of Anaplasma
and are "immune carriers. Dose rate of 2 mL i/v and is given at 6-12 month
of age. Booster doses are recommended every 1-2 years depending on herd history
(Ristic, 1960).
Vaccines against giardia
GiardiaVax: It is a killed culture trophozoite vaccine for dogs and prevent
the disease and shedding of Giardia lamblia. The vaccine is derived from
G. duodenalis isolated from sheep. Dose of vaccine is 1ml by subcutaneous
route. First dose at 8 weeks of age and second after 2-4 weeks and then repeated
annually. Dogs which had failed to be cured of giardiasis following chemotherapeutic
measures were treated with a Giardia vaccine (2-3 injections). After
immunization, the clinical signs diminish within 16-42 days, therefore it is
a good method for treating giardiasis in dogs.
Vaccines against babesia: It is live attenuated vaccine, developed by
in-vitro culture (Levy and Ristic, 1980). Cattle
were vaccinated with exo-antigen from culture (MASP) elicit humoral and cell
mediated immunity (Alexis et al., 1993).
Pirodog/Nobivac® Piro: It is a Soluble Parasite Antigen
(SPA) of supernatants of in vitro cultures (B. canis and B.
rossi) gives 80% protection and immunity last for about 6 months (Schetters,
2005). It is given at 6 months of age and booster vaccination is required
3 to 6 weeks after the initial vaccination and thereafter revaccination every
6 months by intramuscular route. Both the vaccine produces some local reaction
at the site of injection but this reaction is more in case of Nobivac Piro vaccine
(Freyburger et al., 2011).
Vaccine against neospora: An ideal vaccine have to provide protection
against both infection and the clinical signs, so there is requirement of vaccine
that can induce a non-foetopathic cell mediated immune response (Goodswen
et al., 2013). Recently, a Neospora caninum killed tachyzoite
based vaccine has been reported to be efficacious in preventing abortion in
dairy cattle (Williams et al., 2007; Weston
et al., 2012). Proteins, which have important role in adhesion/invasion
or other parasite-host-cell interaction processes can provide protection against
Neospora infection and can be targets for the development of an effective vaccine
against this important protozoan parasite (Hemphill et
al., 2013).
Bovilis® Neoguard: It is prepared by killed tachyzoite
of Neospora caninum with spur adjuvant which reduces abortion in cattle by more
than 50% (Meeusen et al., 2007; Weston
et al., 2012) but may increase the early embryonic death, if used
in pregnancy (Weston et al., 2012). The vaccination
induce antibody at a high level which give protection upto 1 year, so booster
vaccination after 1 year is required. It is administered in two doses of 5 ml
at one month apart, the first dose given between day 75 and 90 of gestation,
booster in 3-4 weeks with 2 annual boosters 3-4 weeks apart by subcutaneous
route.
Live tachyzoite vaccine: Tachyzoites were maintained under conditions
in a continuous passage of vero cell-lines at 37°C and 5% CO2
in air and in RPMI 1640 medium supplemented with 2% horse serum and penicillin-streptomycin
(100 IU mL-1 100 g mL-1). This vaccine protects the losses
due to death of foetus (Williams et al., 2007;
Hecker et al., 2012; Goodswen
et al., 2013).
Vaccines against toxoplasma: Effective vaccines against Toxoplasma
gondii, a protozoan parasite infecting both animals and humans, are very
helpful in preventing and controlling toxoplasmosis (Innes
et al., 2009; Liu et al., 2012).
Invasion factors of T. gondii viz., microneme protein 6 and 8 (MIC6,
MIC 8) have also been proposed to be a useful vaccine contender for toxoplasmosis
(Peng et al., 2009; Liu et
al., 2010). Some experimental trials have been going on the protective
efficacy of recombinant T. gondii PDI (rTgPDI) as a vaccine candidate
for combating toxoplasmosis (Wang et al., 2013).
S48 strain (Toxovax): It is a live vaccine containing originally isolated
tachyzoite from aborted placenta and maintain in laboratory by repeated passage
in mice. It was initially developed for sheep but in cats it inhibits sexual
development of T. gondii (Verma and Khanna, 2012).
Loss ability to form bradyzoites or oocysts and eliminated within 14 days by
host immune response (INF-gamma). The S48 strain when ingested by cat after
voided by cat does not cause production of oocyst. It prevent from spreading
in the body; placenta as well as meat contamination for 18 months. It is given
4 weeks before mating by intramuscular injection on the neck (OConnell
et al., 1988). It should be given @ 2 mL intramuscularly. Basic vaccination
should be given as single dose at least 3 weeks prior to mating. Re-vaccination
after 2 years with a single dose atleast 3 weeks prior to mating is recommended.
T263: It is a bradizoite of live mutant T. gondii that does not
formed an oocyst. The administration of T263 yield leads to reduction/prevention
of oocyst shedding in cats (Verma and Khanna, 2012).
Vaccine against Theileria: The process of development of Theileria
annulata cultures involves cultivation of the organism for a prolonged time
(Pipano and Tsur, 1966). The organisms are collected
from the infected animal either by Lymph node biopsy or whole blood. The in
vitro culture yields agamogenic strain of the organism. This cell culture
attenuated vaccine (Rakshavac-T) has an efficacy approaching 95-100% (Brown
et al., 2006). The site for inoculation is mid-neck region@
3 mL. Calves of 2 months age and above only should be vaccinated. This vaccine
should not be used in advanced stage of pregnancy. Attenuated schizont vaccine
are effective in prevention of theileriosis in cattle (Barriga,
1994; Pipano and Shkap, 2000) however more safer
and effective vaccines need to be developed utilizing advances in molecular
tools and techniques for control of theileriosis in bovines and ovines (Yin
et al., 2008). Vaccines against Bovine theleriosis caused by Theileria
parva should be mixture of several antigens derived from both sporozoite and
schizont stages, leading to strong immunity (Morzaria et
al., 2000).
Vaccine against Leishmania: Different types of vaccines for prevention
of leishmaniasis have been developed (Brodskyn et al.,
2003; Coler et al., 2007; Nagill
and Kaur, 2011).
Leishmanization: It is inoculation of exudates from the active lesion
of an infected person to non-infected susceptible person to give an immunization.
It has been use from older times but the use is now limited.
Killed vaccine: The killed promastigote are use for immunization with
or without BCG. Leishmania braziliensis promastigote killed by autoclaving
give good results.
Leishmune: It blocks the transmission of canine visceral leishmaniasis
(Nogueira et al., 2005). It has gp63 protein
of L. donovani that is adjuvanted in saponin (Parra
et al., 2007). This vaccine has 76-80% efficacy. It is transmission
blocking because:
• |
The number of Leishmania protozoa in the skin of a
dog is reduced in number. Thus the Phlebotomine flies does not readily get
the the protozoa during blood feeding |
• |
The antibody produced does not allow the development of an infective promastigote
inside the fly vector |
Leish111f: One of the most promising finding is the recombinant protein
called Leish 111f along with an adjuvant MPL-SE (Monophosphoryl Lipid-stable
emulsion) shown by Coler et al. (2007). It is
a recombinant protein of:
LeIF: |
L. braziliensis initiation and elongation factor |
TSA: |
Thiol-specific antioxidant |
LmSTI1: |
L. major stress inducible protein |
The Leish 111f is having an added advantage like the vaccine efficacy is very
high reaching upto 99.6%. Another is that it gives cross protection i.e., Leishmania
donovani, which can be also used as a therapy especially trial in man. In
mucocuteneos Leishmaniosis caused by L. briziliensis and other cuteneous
Leishmaniosis. But the treatment schedule takes a very long time.
Vaccines for Sarcocystis:
EPM vaccine: It consists of in vitro cultured merozoites, obtained
from the spinal cord of horse, which are chemically inactivated and mixed with
suitable adjuvants (Marsh et al., 2004). It
gives protection against a neurological disease in horses caused by infection
with Sarcocystis neurona, equine protozoal myeloencephalitis. It is given@
1 mL intramuscularly and booster vaccination 3 to 6 weeks after the first dose,
then revaccination annually.
S. neurona SAG1 protein vaccine: It is subunit vaccine prepared
from major Surface Antigen Gene 1 (SAG1), which is conserved among members of
Sarcocystidae (Elsheikha and Mansfield, 2004). Horses
were vaccinated on days 0 and 21 with 1ml adjuvanted rSnSAG1 (50 μg) or
1 mL adjuvant alone by intramuscular injection in the left side of the neck
(Ellison and Witonsky, 2009). Booster vaccination is
required after 3 to 6 weeks of the first dose and then revaccination annually.
Vaccine against Trypanosoma:
Beta-tubulin: The beta-tubulin gene of Trypanosoma evansi (STIB 806)
was cloned and expressed in Escherichia coli (Li
et al., 2007). Beta-tubulin is important for cellular structure
and physical functions. Recombinant beta-tubulin was expressed as inclusion
bodies in E. coli.
TSA (T. brucei DNA vaccine encoding TSA Protein): The DNA vaccination
process was able to protect 60% of mice submitted to a challenge assay with
the infective form of T. brucei brucei parasites (Silva
et al., 2009).
MAPp15 (Microtubule associated protein): In an experimental study, vaccination
of mice with p15 (native or recombinant) provides complete protection from Trypanosoma
brucei suggesting it as an effective vaccine (Rasooly
and Balaban, 2004).
Vaccine against Tritrichomonas Foetus
Trichguard: It is killed protozoan vaccine for cattle for prevention of
infection by Tritrichomonas foetus. It is given to cattle @ 1-2 mL subcutaneously,
booster vaccination 2-4 weeks after first dose and then revaccination annually.
The last injection should proceed the breeding season by 4 weeks.
COBWEB FOR VACCINE DEVELOPMENT AGAINST PROTOZOAN INFECTION
There are lot many factors which causes the pitfall for development of a successful
protozoan vaccine which is of the supreme importance to keep infection at the
gate way. The important factors are pathogen associated, vaccine market associated
or funding (Vercruysse et al., 2007). Among
all the factors pathogen associated problems needs to be dealt in a more scientific
and clever way as some protozoa are clever enough to escape the immune system.
One of the most important protozoa of this type is the Trypanasoma spp.
which causes a serious problem in case of animals as well as humans (Vanhamme
et al., 2001; La Greca and Magez, 2011).
One of the noteworthy features of this protozoa is that it can change its antigenic
surface protein in such a rapid manner so that the immune system of host cannot
trace it (Pays et al., 2004). Many protozoa
also have a complex life cycle during their survival in the host. Two stages
of life cycle namely sexual and asexual exist in the life pattern of many protozoa
and hence selecting a vaccine candidate becomes a difficult task. Certain situation
occurs when a single host cell have protozoa at different stages of development
giving a feel to the host immune system that there a number of protozoa in a
single cell (Vercruysse et al., 2007).
CONCLUSION
Drugs remain central to alleviating clinical disease and for larger scale disease
control programmes. However, available drugs have often been in use for decades
and drug resistance in the target parasites is now prevalent and, particularly
in the case of livestock, threatening sustainable control. Control is threatened
by the widespread appearance of drug-resistant parasites in animals. Development
of drug resistance could limit the use of anti-parasitic drugs which will remain
important for a long time. Drug residues found in the food animal, development
of drug resistance and lack of development of new drug are all major problems
or reasons which diverts the scientist to make efforts on vaccine development
related research. Many vaccines are included in the control of parasitic diseases
programs, as these approaches may lead to a substantial reduction in the use
of chemical drugs for prevention and control of parasitic diseases. The need
of hour is to apply the immunization results of murine/lab animal model in veterinary
science and for humankind. Vaccination may also aim to improve public health,
so there is a need of cheap and effective vaccine to be developed and reach
with success in the market. Development of vaccine against protozoan parasite
is cumbersome process because of their complex life cycle, many developmental
stages and sub clinical form of disease. Efforts for making economically feasible
and effective protozoan vaccine, strategies to discover new antigen to act as
novel vaccine candidates are still in continuation.
|
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