Worldwide leptospirosis is a widespread disease of livestock,
domestic pet and animals caused by sprirochete bacteria Leptospira
interrogans. Humans get infection accidentally by exposure to
infected animals tissues, urine etc (Prabhu et al., 2015). Sporadic
cases and outbreaks of the disease have been reported in many
parts of India. The disease is general in domestic animals including
cattle, buffalo, sheep, goat, dogs and equines and causes fever
and its related illnesses, jaundice, acute to chronic renal failures,
reproductive disorders and increasing mortality (Kamath and
Dikken, 2003). Recurrent abortion, hypoprolactin (suppression of
lactation) and mastitis are observed among animals giving milk
The first case was reported with the clinical history of jaundice
in Andaman Islands, followed by the isolation of Leptospira
interrogans serovar Icterohaemorrhagiae in Madras city. Further,
more reports have been recorded to confirm the prevalence of
leptospirosis in various other animals and humans. In India, the
infection pocket was initially determined as the coastal regions
of Kerala, Tamil Nadu, Gujarat, Orissa, Mumbai, Uttar pradesh
and Andaman Islands (Sehgal et al., 2001; Karande et al., 2002).
The serological confirmation of the presence of antibodies against
the infective serovars autumnalis, grippotyphosa, hebdomadis,
javanica, pomona, pai and sejroe were recorded in southern part of
India (Koteeswaran, 2006). Some studies highlighted the increase
in leptospiral infections in animals and humans in various parts
Prevention of leptospiral infections among animals and humans
are considered as long-term strategies that adopt the importance of
rodent control, a major source of infection followed by individual’s
and environmental hygiene (Srivatsava, 2006). Vaccination is
also a very important area to be developed as a prime segment
in the prophylactic evaluation (Broom, 1949). Technically, the
urgent requirement of the newer and effective vaccines may help
to control the infection in animals in husbandry, pet animals and
cattles to control the spread of infections to humans. Currently
available commercial vaccines for leptospirosis are quite effective
by providing serovar specific immunity and are used in many
developed countries (Wang et al., 2007). The generation of
serovar specific immunity is the major drawback observed where
the animals become carriers for leptospirosis (Brunnet and Meyer,
1950). The animals in the community should be targeted for
vaccination economically and effective management. Most of the
studies suggested for the usage of inactivated or attenuated whole
culture vaccine for effective functioning (Christopher et al., 2011).
More number of leptosprial vaccines have been identified and
evaluated among risk group of animals where the usage of
inactivated leptospiral serovars is quite common (Wang et al.,
2007). Heat killed, phenol inactivated, lyophilized serovars,
formalin inactivated, acetic acid heat extraction and multi time
sub cultured pathogens are trialed leads to unsuccessful and
no cross protection identified. To overcome this issue, multiserovar
vaccines have been introduced and successfully tested
on experimental animals. A good and effective observation was
made towards the usage of formalin inactivated multi-serovar
preparations with adjuvants and acetic acid heat extracted vaccines
provide significant high titres lead to successful resistance towards
infection (Kaminski et al., 2014). In some instances, shedding of
leptospries in the urine of the animals observed even multi-valent
vaccines provides high MAT titre leads to the observation of non
efficiency of this type of vaccines (Vallee et al., 2016).
The trivalent vaccine comprising pomona, copenhagen and hardjo
was highly immunogenic and induce high titres but the efficacy
is doubtful; thus further measurement of fertility performance
and milk yield may provide some effective idea to understand
the mechanism and specific action of the vaccine (Venugopal and
Ratnam, 1991). Some studies highlighted the usage of bivalent
vaccine leads to the protection of animals form the infection and
reduction in shedding of leptospires in the urine. Thus the usage
of multivalent vaccines is useful in covering infections caused by
multiple serovars but it was doubtful that it is effective against
all infective serovars. The successful continuous vaccination with
intermittent time may be effective to avoid the local swelling and
reducing adverse reactions in animals and humans (Poland et
al., 2003). The chemical inactivated whole cells of canicola and
icterohaemorrhagiae has produced allergic responses by inducing
IgE antibodies. Sometimes the inactivated serovars are ineffective and may cause infection to the recipients. More vaccines are
available for canine leptospirosis induces the MAT titres not only
against the specific serovars used for vaccine preparation but
also cross reaction observed leads to misdiagnosis of the disease.
Pomona vaccine is the first attenuated live vaccines that are largely
used for cattles and observed in the reduced abortion rate.
The gamma irradiated leptospires were competent towards
producing agglutinating antibodies and showed high protection
from mortality and infectious nephropathy (Cumberland et al.,
2001). Other study highlighted that chemically inactivated vaccine
is effective than the irradiated vaccine; in both cases, the vaccines
were serovar-specific, further no confirmation was found in this
scenario. Synergestic observation of irradiated pomona with 60 ug/
ml dihydrostreptomycin was carried out leads to high protection in
animals where no shedding of leptospires observed after 14 days,
the another set of animals with irradiated Pomona aloe leads to
establish renal infection. The attenuated live vaccines were capable
of stimulating higher titers than chemically inactivated leptospiral
serovars, further have not gained wide usage among veterinary
biologic manufacturers and are probably due to difficulty of
maintaining the viability upon storage as well as the possible
reversion to the virulent state in the host animal (Cumberland et
The subunit vaccine using the outer envelope of the leptospires by
sodium dodecyl sulfate method is having primary target for antibody
complement action. The degeneration and mutation of the outer
membrane is not possible due to its detachment with intracellular
organization and completely removed from protoplasmic cylinder
(Oliveire et al., 2015). Thus this is very effective, protective and
providing satisfactory immunogenic potency in experimental
animals than other types of preparations. Further studies also
suggested that the protein fractions of the outer membrane are least
effective leads to the sensitization of lymphocytes, as monitored
by blast transformation. A recent study suggested that the outer
membrane proteins (a hydrophobic protein) of the whole fraction
among pathogenic leptospires generated cross protection among
various serovars, a novel thought in the new vaccine preparations
that confer a solid immunity against challenge similar to that
observed with a whole cell vaccine (Oliveire et al., 2015).
Some studies suggested that the vaccination of guinea pigs
with DNA recombinant plasmid protected against virulent L.
interrogans serovar Lai. Due to the presence of most abundant
protein expressed gene in pathogenic leptospires, the production
of recombinant vaccines is quite useful and easy for the production
of effective immunogen (Parthiban et al., 2015). Adenovirus
expressed protein has been identified and reported to induce
significant level of protection in experimental animals. The
virulent-associated surface exposed outer membrane proteins like
Lig A and Lig B consists only of Ig like domains and an additional
unique domain at the C-terminal respectively (Oliveira et al.,
2016). Expressing the gene in the eukaryotic models are also now
expanding of understand the synergistic attempt.
The protection capacity of carbohydrate composition of
lipopolysaccharide (LPS) in leptospiral outer membrane with
Freund’s incomplete adjuvant reflects the antigenic diversity
among pathogenic leptospires showed serovar specific immunity
(Tadjine et al., 2004). The extensive study in the determination of
effectiveness of pentavalent vaccine and LPS showed lesser and
effective action on leptopiral infections. But one study suggested
that the protection against pathogenic serovars is observed while
administrating LPS from L. biflexa serovar patoc. Thus this is
indicative of the protective efficacy of LPS but more studies are
needed to prepare large scale or clinical trials (Patra et al., 2015).
A new promising approach of DNA encoding leptospiral proteins
with adjuvants for vaccination against leptospirosis is now in
research and trial for producing immune-modulation. The major
constraints in leptospirosis vaccine development and use are
1. Continuous epidemiological monitoring is not done at zonal
levels for conferring serovar specific immunity
2. In most of the places, the facilities for performing MAT is not
available; MAT may be useful in investigating serovar-distribution
provided antibodies are monitored at regular intervals.
3. While investigating the seroprevalence, care should be taken in
interpreting the results since no test can differentiate antibodies
generated in animals after the vaccination from those developed
after an infection.
4. Selection of monovalent serovars is not effective against
multiple serovars of the leptospiral pathogens. Controversially,
may suppress the immune response
5. Repeated booster immunization may not provide sufficient
immunity against such serovars.
6. The development of leptospirosis vaccines is an arduous and
time-consuming process due to the requirement fastidious growth
7. In laboratory or in pharmaceutical set up, the bulk promotion of
organisms may not be achieved satisfactorily.
8. For testing the potency of veterinary biologicals, requirement of
large number of hamsters.
9. This is time-intensive and has large associated rest variances.
10. The usage of animals for experimentation is already restricted
by the Government, thus successfulness of performing in vitro and
in vivo tests are cumbersome.
The urgent need of constructing a novel and newer leptospiral
vaccines are quite important. From this review, it was identified
that the membrane proteins have been increasingly found to be
protecting from leptospirosis.
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