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Human
Parasitic
Vaccines
Dr.M.Muruganandam
Human Parasitic Vaccines
Dr.M.Muruganandam
First Edition -2019
ISBN-978-9982-22-635—6
Publisher
Einsteein Bio-Engineering
Research Foundation.
Author
Dr.M.Muruganandam,
Email- [email protected]
www.vaccinebiotech.blogspot.com
Preface
Human parasite vaccine
development research is going on around the
world. Still scientists are not reach
appropriate level. Because parasites have
Complex life cycle and they need to complete
their life cycle with the help of different host.
In this book, informations are collected from
various researchers regarding current status
of Parasite vaccines. I thank all of them. I
hope this manuscript will be useful to vaccine
development researchers. Once again thanks
to all.
M.Muruganandam
Content
1. Parasitic disease Burden
2. Obstacles in vaccine Development
3. Malaria Vaccine
4. Leishmaniasis Vaccine
5. Amoebiasis Vaccine
6. Cestode Vaccine
7. Schistosomiasis Vaccine
8. Hook worms vaccine
9. Filariasis Vaccine
10. Prevention and control methods.
1. Parasite Disease Burden
Parasite infections are the leading cause of
morbidity as well as mortality in developing and
under developed countries in the world. In the
most places, the infected peoples are children,
aged people and pregnant women who are due to
weakness and poor immunity. Another important
reason is lack of awareness about infections such
as malaria, Leishmaniasis, etc and People are not
followed by proper prevention methods. 1
The intestinal and protozoan infections are the
most parasitic diseases with according to WHO,
3.5 billion people affected and 450 million,
mainly children ill as a result, Co-infection with
different parasites is common and illness is often
made worse by Co-existing malnutrition.2
The parasites have different types of antigens.
The antigenic variations posses a big problem
during vaccine development. The most of the
parasitic infection leads to immuno suppression
in host. The important antibodies such as IgA,
IgE and IgG play a key role in parasitic immune
responses. The polymorphic nuetrophill and
Eosinophils also plays an important role in cell
mediated immunity.
The parasitic vaccine development is
complicated process, because parasites have
various stages in life cycle in host and Vector.
So identification of proper Immunogens are very
difficult. However many attempts in vaccine
development is going on in all over the world.
The current status of vaccine development is
discussed here.
Reference
1. Muruganandam .M and N. Thiru Kumari (2016) malaria - A
climate sensitive disease - Proceedings of the Seminar on Global
warming and climatic changes held on 19th Aug.2016. pp. 87-91.
2. Knox. D.P.(2010). Parasite Vaccines: Recent progress in the
problems Associated with their development. The open. Infect.
Disease. jour. 2010,4; 63-73.
2. Obstacles in vaccine Development.
The existing anti - parasitic drugs have
been in use for decades and drug resistance
among the parasites in gradually expanding
the glaring example of which can be seen in
Plasmodium falciparum. The important
obstacles for vaccine development are as
follows.
Even the simplest parasites have complex
structure and life cycles.
There is a general lack of precise
understanding of the host/parasitic
interaction.1
Due to complex nature of parasites the
immune system is confronted with a highly
diverse and continuously parasite changing
the spectrum of antigen.
A number of biological characteristics of the
parasite help in making the situation more
difficult, many parasites go through a phase
of sexual reproduction, with the associated
exchange of genetic material. This results in
new parasites with a different genetic and
phenotypic makeup.
There is a different expression of genes
during the successive life cycle stages. This
will create difficult situation to host immune
system for understanding the nature of
Immunogens.
A number of species can express distinct
various stages - Specific molecules which are
antigenically different. This ability allows
them to avoid the host defence mechanisms.
Parasites avoid, deflect and confuse host
immune system; the right parasite antigen has
not been identified yet because of
complicated life cycle.
The protective host responses are not
understood in most target species. These
parasites candidate antigen also may show
their efficacy.
Absence of genome databases or
bioinformatics algorithms for selecting
candidate antigens of promise.
Another thing is the commercial viability of a
vaccine depends on such factors as
development and production casts, and
specific characteristics, such as storage,
transport conditions and shelf life.
Current drugs have efficacies approaching
100%: - It will not easy to persuade users that
a vaccine which less than 100% effective can
usefully control the disease2.
Reference
1. Vercruysse.J., Schetters, Tpm,Knox.D.P,Will Adsen,P,Clae
rebout.E. Control of parasite disease using vaccines: an
answer to drug
resistance?Rev.Sci.tech.off.int.Epiz.2007;26:105-115
2.Abhijit Chaudhury(2014).Human parasite vaccine-an
overview .J.clin.Bio.Sci. 2014;4(1):216-21.
3. Malaria Vaccine
3.1. Malaria
Malaria is the world's most important
tropical parasitic disease. The world wide
prevalence of the disease is in the order of 350 -
500 million clinical cases each year, with an
estimated annual death toll of over |:| million
deaths reported by WHO. Plasmodium is an
unicellular organism. It causes malaria. It is an
endoparasite living in the blood of man. It is
cosmopolitan in distribution. Plasmodium
completes its life cycle in two hosts, namely
man and the female Anopheles mosquito.
The life cycle of plasmodium in man is called
the cycle of Golgi. It occurs in three stages.
They are 1. Pre-erythrocytic cycle 2. Exo-
erythrocytic. Cycle and 3. Endoerythrocytic
cycle. Another one Cycle Present inside is the
mosquito called cycle of Ross.
3.2 Vaccine
The development of Vaccine for malaria has
turned out to be a highly complex exercise
owing to a multitude of difficulties. (1). A natural
malaria infection does not repeated and
prolonged exposure to malaria parasite over
several years, only partially effective immunity
is acquired, which is short lived and is highly
stage and strain specific. (2,1). This incomplete
immune response is due to the complex biology
of the plasmodium parasite. Its extensive
antigenic diversity and its immune evasion
strategies and all these factors make vaccine
development against malaria challenging (3).
Several vaccine candidates have been
tasted over the years, but without much success.
Now few malaria vaccine candidates entered in
clinical trials. The difficulty of developing a
highly effective malaria vaccine has led to the
design and assessment of a very wide range of
new approaches (1).
3.3. Irradiated Sporozoites
The observation that inactivated plasmodium
sporozoites could protect against malaria is
about a hundred years old. However, Systematic
demonstration of protection using irradiates
sporozoites occurred in the nineteen - sixties,
providing the impetus for the development of
malaria vaccine. Modern malaria vaccine
development works starts from immunization
studies of mice with irradiated sporozoites,
conducted in the 1960s (4). A high level of
protection could be induced in volunteers, but
required large number of bites by irradiated
infectious mosquitoes (2). Immunization of the
human subjects with irradiated sporozoites
confers high levels of protection against
experimental infection, suggesting that
vaccination is feasible.
Individuals in malaria endemic countries do
acquire, natural immunity that builds up slowly
requires continual antigenic stimulation and
affects the severity of disease (5). Protection has
been elicited by passive transfer of hyper
immune immuno globulins from malaria
immune adults into malaria native human
volunteers.(6).
3.4. Peptide Vaccine
In 1983, the circum sporozoites protein (CSP) , a
major sporozoites surface antigen became the
First plasmodium gene to be cloned and a CSP -
based vaccine appeared. The emergence of a
peptide based candidate vaccine from Colombia
called SPf66, with apparent efficacy in new
world monkeys and humans (2). Different
recombinant proteins are used as vaccine
candidate. They receive only limited success.
3.5. Apical membrane Antigen - 1
Apical membrane antigen - 1 (AMA-1) is
another leading candidate. It is present in a type.
I transmembrane Protein located in the
micronemes of the merozoite that is functional
in the rapid invasion of erythrocytes (8). Pre-
Clinical studies showed that Vaccination with
AMA-1 induces antibodies and protection
against homologous parasite challenge in both
rodent and monkey models of malaria infection
(9, 10).
Vaccination of monkeys with recombinant
plasmodium falciparum apical membrane
antigen -1 confers protection against blood stage
malaria. The outcome of a phase 1/2 a study,
which evaluated the safety, immuno genicity and
efficacy of a vaccine compressed of a
recombinant plasmodium falciparum AMA -1
representing the 3D7 allele formulated with
either the AS01B or ASo2A adjuvant system just
been reported (II).All vaccine formulations
stimulated similar functional antibody responses,
as judged using a growth inhibition essay against
homologous parasites and demonstrate
interferon - gamma (IFN - gamma) responses.
However, volunteer’s challenges with
P.falciparam infected mosquitoes all become
parasitimic although a small but significant
reduction of parasite in the AMA-1 ASo2 A
group was noticed.
3.6. Transmission Blocking Vaccine.
It induces antibodies against the sexual stage
antigens which prevent the development of
infectious sporozoites, the salivary glands of
Anopheles mosquitoes. The leading candidate
vaccine contain the P. falciparum surface
protein antigens Pf S25 and P fs28 or offer
P.vivax homologous PVS25 and PVS -28(7).
These vaccines are currently being developed at
the NIH as recombinant yeast secreted proteins.
(S. Cerevisiae). Initial human phase I trials have
been conducted for Pf s25 and should follow
soon for PVS25. Other sexual stage - specific
antigens that are being developed as
transmission - blocking vaccines are PfS48/45
and Pfs230.
The concept of attenuation and parasite
challenge to elicit immunity is also being
explored. As noted earlier, an attempt to develop
a commercial attenuated sporozoites vaccine has
been under taken by Sararia Inc. with the
support from the Bill and Melinda Gates
foundation and the NIH and the outcome of
clinical trials is a waited.
3.7. Erythrocytic Vaccine.
A sexual blood stage strategies aim to elicit
antibodies that will inactivate merozoite and or
target malarial antigens expensed on the RBC
surface, thus inducing antibody dependent
cellular cytotoxicity and complement lysis; they
also are meant to elicit T Cell responses that will
inhibit the development of the parasite in RBCs.
This type of vaccine would mostly serve as a
disease reduction vaccine in endemic countries
by decreasing the exponential multiplication of
merozoites.
The development of MSP-1 as a vaccine
candidate is the subject of a recent detailed
review (12). Briefly, MSP, conferred production
against challenge infection against plasmodium
yoelii in the laboratory mice 13 and passive
immunization with monoclonal antibodies
(MAbs) also provided in the same model,
highlighting in the importance of antibody for
production. (14,15).
Gene sequence analysis (16) allowed detailed
structural analysis which identified a disual
phide - rich region of approximately 100 amino
acids at the C - terminus which encoded 2
epidermal growth factor (EGF) domains (12).
Subsequent work showed that immunization
with recombinant forms of the EGF domains
protected against challenge infection with blood
stage rodent parasites (17). Evidence that MsP-1 is
important in natural acquired immunity and can
consistently confer protective immunity is
equivocal.12.
3.8. Pre - erythrocytic Vaccine.
Pre - crythrocytic Vaccine strategies aim to
generate an antibody response that will
neutralize sporozoites and present them from
invading the hepatocyte and /or to elicit a cell
mediated immune response that will inhibit intra
hepatic parasites. This type of Vaccine would
prevent the advert of clinical disease. The most
advanced Pre-erythrocytic (liver stage) vaccine
candidate is derived from the circum sporozoites
Protein. (CSP). The major component of the
surface of the sporozoites Prototype Vaccine
were designed to induce antibody responses
against the repeat epitope of the circum
sporozoites protein and provided the first
evidence that humans could be Protected from
malaria infection with a sub unit Vaccine.(18,19).
The candidate Vaccine were poorly
immunogenic and a vaccine was developed
comprising a typhoid of the circum sporozoites
protein fused to hepatitis B surface antigen
expressed together with unused HBAg (20). From
these prototypes, RTS, S/A SO2 arose, which is
composed of both the CSP repeat antibody
targets as well as C-terminal non- repeat regions
that pre-targets for cell mediated immunity (21).
These were fused to the hepatitis B surface
antigen and expressed in yeast(21). Initial Phase -
I clinical trial of RTS, S formulated with Glaxo
Smith - Kline ASO2 adjuvant, an adjuvant
vehicle which consists of a lipid emulsion,
showed protection against malaria challenge in
six out of seven volunteers.(5).
More recently, the Vaccine has been formulated
with ASO1, A liposomal vehicle and this
vaccine induced higher levels of antibody and
Th1 response to the GS Protein (22). Vaccination
with these formulation Protects against infection
and reduces blood Parasites Extensive clinical
studies are under way, including one aimed at
combining RTS, with a blood stage antigen
MSP-1 (21). The MSP -1 is expressed on the
merozoite surface and is also a target for
protective immunity (12).
Reference
1. Hill. AVS. Vaccines against malaria. Phil Trans. R. Soc. 2011;
366 : 2806-14.
2. Patarroyo, ME. Et al., 1988. A synthetic Vaccine protects
human against challenge with a sexual blood stages of
plasmodium falciparum. malaria. Nature. 1988; 332:158-161.
3. Stoute.J.A., A Preliminary evaluation of a recombinant circum
sporozoite Protein Vaccine against Plasmodium falciparum
malaria. RTS. S. Malaria Vaccine Evaluation. Group. N. Engl.
J. med. 1997; 336 : 86 -91.
4. Nussen Zweig. R.S. Vanderberg . J. Most. H, orton. C,
Protective immunity Produced by the injection of X-irradiated
sporozoites of Plasmodium berghel, Nature 1967; 216; 160-
162.
5. WHO, 2008. Immunization, Vaccines and Biologicals.
6. M C Gregor. IA. The Passive transfer of human malarial
immunity. Am.J. Trop. med. Hyg 1964. 13. Suppl.237-9.
7. Wu. Y., Ellis, R.D, Shaffer. Detal Phase - I trial of malaria
transmission blocking Vaccine candidates Pfs25and PVS25
formulated with motanide I SA51, PLO some 2008;37:2636
8. Tree CK.M., Zacheri.S, Herrmann.S., et al., Functional analysis
of the leading malaria vaccine canditate AMA - 1 - reveals an
essential role for the cytophesmic domain in the invasion
process pLos pathog 2009:5(3): e 1000:322.
9. Collins.W.E., pye.D., crewther.P.E., et al Protective immunity
induced in squirel monkeys with recombinent apical membrane
antigen - 1 of plasmodium fragile Am.J.Trop.med.Hyg.1994.51:
711 - 9,
10. Stowers.Aw, kennedy, M.C., Keegan.BP., soul.A., Long.CA,
miller.L.H. vaccination of monkeys with recombinant
plasmodium falciparum apical membrane antigen - 1 confers
protection against blood - stage malaria Infect Immun.2002: 70:
6961-7.
11. Spring, MD., Cummings, J.F., ockenhouse CF. et al., phase 1/2
A Study of the malaria vaccine candidate apical membrane
antigen - 1 (Ama -1) administrated in adjuvant system A sol B
or Aso2A PLoS one 2009; 4(4): e 5254.
12. Holder AA. The carboxy - terminus of merozoite surface
protein.1. Structure, Specific antibodies and immunity to
malaria, porasitology .2009; 136: 1445-46.
13. Free man.RR. Holders.AA., charcteristics of the protective
response of BALB/C Mice immunized with a purified
Plasmodium yoelii. Schizont antigen clin.Exp. Immunol . 1983;
54; 609 - 16.
14. Maharajan. W.R., Daly. Tm, We idenzwp, Long. CA., Passive
immunization against murine malaria with an IgG3 monoclonal
antibody I. Immunel. 1984; 132; 3131 - 7.
15. Spencer valero.L.M., ogun SA, Fleck.S.L, et al., Passive
immunization with antibodies against three distinct epitopes on
plasmodium yoeliii; merozoite surface protein I. suppresses
parasitemia Infect immun. 1998; 66: 3925 - 30.
16. Holder. AA., Blackman.MJ, Burghaus.P.A chappel JA, Ling .
IT, Mccallum Deighton.N sha.SA., Malaria merozoite surface
protein (MSPI) - structure, processing and function. Inst.
oswaldo cruz. 1992; 87 (suppl.)3: 37 - 42.
17. Daly. T.M.., Long. CA, Humoral response to a carboxyl-
terminal region of the merozoite surface protein – I, plays a
predominant role in controlling blood stage infection in rodent
malaria. J. Immiunol. 1995; 155 – 236-43.
18. Hoffmann. SL, wistar.R. Jr. Ballon. WR. Et al Immunity to
malaria and naturally a cqwired antibodies to the circum
sporozoites protein of plasmodium falciparum. N. Engl. J.med.
1086: 315: 601-6.
19. Ballon. WR., Hoffman, Sl, Sherwood. JA et al., Safty and
efficacy of a recommend DNA plasmodium falciparum
sporozoites vaccine Lancet. 1987; 1 (8545) ; 1277-81.
20. Stoute. H.A., Sla ow,M., Heppener DG. et al., preliminary
evaluation of a recombinant circum sporozoites protein vaccine
against plarmodium falciparum malaria. RTS. S. Malaria
vaccine Evalzation Group. N. Engl. J.med. 1997; 336; 86-91
21. Ballon, WR. The development of the RTS. S, Malaria vaccine
candidate challenges and lesion. Parasite. Immunol.2009; 31;
492-500.
22. Garzon.N, Heppener DG, Coten. J., Development of RTS,
S/ASo2, a purified sub-unit based malaria vaccine candidate
formulated with a novel adjuvant Export Rev. Vaccines. 2003;
2231-8.
4. Leishmania vaccine
4.1Leishmaniasis
It is caused by several species of flagellated
protozoan parasites of the Leishmania genus, is
prevalent in Africa, Latin America, south and
central Asia, the Mediterranean basin and the
middle east,. There are an estimated 12 million
cases annually and disease can cause serious
disfigurement as well as death. Parasite are
usually transmitted from a wild animal
reservoirs (Small rodents, dogs) by biting sand
flies although transmission can occur from
infected humans the disease has Cutaneous,
mucocutaneous and visceral forms. About 1.5 –
2 million occurs annually and epidermis of
visceral leishmaniasis canaries with mortality
rates. The treatment relies on chemotherapy is
expensive and becoming compromised by
emerging during resistance. Recovery from
infection renders an individual resistant to
subsequent infection indicating that a successful
vaccine is feasible (14). As noted earlier
vaccination is possible with by controlled
infection using infectious materials from lesions.
(1).
4.2 Vaccine
The evidence is that most individuals who
were once infected with Leishmania are resistant
to clinical infections. When later exposed to it
provided the just infection for vaccine
development (2). The leishmaniasis are unique
among parasitic disease because a single vaccine
could successfully present and treat diseases and
the potential to protect against more than one
leishmania parasite species (3). There are
different types of vaccine development process
is going on. Here they discussed in details.
4.3 Killed vaccine
First generation vaccines consisting of
whole killed leishmania or fractions of the
parasite. Whole killed vaccines have been
experiment with both old and new world
leishmania. Mayrink and his colleague was
developed a killed vaccine composed of five
isolates of leishmania containing four different
species in 1970 (4). Convict and his group in
Venezuela introduced their autoclaved
Leishmania mexicana (L.mexicana + BCG for
immunotherapy (1).
Several prophylactic studies were done with in
conclusive results or low immunity protection
induced by the vaccine. For old leishmaniasis,
autoclaved L.major BCG (ALM + BCG) has
been extensively studied. Two doses of the
vaccine reduced the incidence by 43% in
Leishmania skin test converted volunteers in
sudan against visceral leishmaniasis involving
2306 volunteers (6). To enhance the.
Immunogenicity of the ALM + BCG vaccine
.ALM was absorbed to alum and the resulting
alum, ALM was mixed with BCG just prior to
injection. It appears to constitute a safe
vaccine and an appropriate candidate for
further development.
4.4. Live vaccine
Live attenuated leishmania vaccine is used
Uzbekistan Iran and Israel. Live virulent L.
major promastigotes are harvested from cultures
and used as vaccine. This is a mixture of live
virulent L.major mixed with killed parasite
registered in Uzbekistan. Adverse side effects
includes development of large persistent lesions,
psoriasis and immunosuperssion (7) Recently use
of L.donovani certain null mutants in mice
showed clearance of virulent challenge parasites
in 10 weeks after challenge, with significantly
reduced parasite burden in the spleen and no
parasites in the liver (8). The use of live virulent
organisms for vaccination was largely
discontinued and in the 1990 s the focus shifted
to attenuated organisms.
Attenuated parasite vaccine are lively to
mimic natural infection and hence induce an
appropriate immune response possible advantage
is that such immunization will also deliver many
more parasite antigens than the limited number
of possible with subunit or recombinant
antigens. (5)
4.5. Sub unit vaccine
A subunit vaccine utilizing the fucose
mannose ligand (FML) antigen has been shown
to be a potent immunogen in mice and rabbit and
a sensitive predictive and specific antigen in
serodiagnoses of human and canine Kala- azar (9)
,the main drawback of subunit vaccine is during
the preparation of vaccine more and more
natural pathogenic antigen subunit is necessary.
So the pathogen must be cultured otherwise,
Isolation and collection of parasitic subunit
antigens are very difficult.
4.6. Recombinant DNA vaccine
Second generation vaccine include all
defined vaccines ie) recombinant proteins, DNA
vaccines and combinations. A variety of
leishmania vaccine candidates consists of
recombinant proteins. More recent efforts have
aimed at increasing the immunogenicity of DNA
cloned vaccine including the use of genetic
adjuvant and plasmid based expression of viral
replicons. Some of the important recombinant
protein candidate vaccine include surface
expressed glycoprotein leishmanolysin (gp63) ,
Leishmania activated C. kinose (LACK)
parasitic surface antigen (PSA) Leishmania
derived recombinant polyprotein (Leish lllf) and
serine proteases (10)
Leish lllf is a single poly protein
composed of three molecules fused in tandem
the L. Major homologue of eukaryotic thiol-
specific antioxidant, TSA; the L. Major stress –
inducible protein – 1 LMSTII; and L.
brazilliensis and initiation factor, Leif. The
Leish- lllf product is the first defined vaccine for
leishmaniasis to go in to human clinical trials
and has completed phase -1 and 2 safety and
immunogenicity testing in normal healthy
human subjects (ll) various subunit recombinant
candidate vaccines have been tested in murine
model of Cutaneous Leishmaniasis (14) A lead
candidate is a surface – expressed glycoprotein
gp 63 or leishmanolysin. This is a zinc
metalloprotease (13) which is expressed on the
promastigotes surface and mediates
internalisation of promastigotes. Efficacy with
recombinant versions has been patchy. (12)
Gp 63 expressed in E.coli induced partial
protection in monkeys (15) However the native
protein purified from L. Major did protect mica
against challenge with either L.mexicana or L.
major and protection was evident when gp63
was expressed in BCG (16) and attenuated
Salmonella. (17) Studies on mice indicated that
host genetics influence the initiation of
protective immune responses to the vaccine (14)
DNA vaccination is considered on attractive
option for vaccine development. Since this
approach generally leads to the induction of the
Th 1responses. (18) A variety of DNA vaccination
is constructs have been test with variable out
comes. In addition, some protective immunity
can be stimulated by vaccination with sand fly
salivary proteins, sand flies being the insect
vector for the parasite with a 15 KD a protein
showing promise (19)
4.7. Ideal vaccine
Given the rapid progress in the fields of
parasite immunology and genetic engineering a
successful anti- Leishmania vaccine should be
achievable in the near future. Kedzierski et al (12)
regarding the definition of an ideal anti
leishmania vaccine. One of the requirements of
an ideal anti leishmania vaccine is to be effective
against more than one leishmania species in
order to protect individuals in areas. Where
Cutaneous and visceral leishmaniasis for
example, co-exist, recent evidence (21) suggests
that cross – Protection is possible.
It is of interest to note that summarizing a
large amount of experimental evidence, Rivier et
al (21) concluded that injection of attenuated
organisms achieved better protection than any
method involving recombinant gp63 as test
antigen delivered with a variety of adjuvant and
delivery systems. The prospect of using
attenuated leishmania vaccine is preference to
submit or recombinant approaches is likely to
come therefore although there would be
problems of are large scale production and
distribution in the field. Based on the past and
present experience on leishmania vaccine
studies, it appears that future experiments should
include appropriate adjuvant as components in
order to achieve effective vaccines against
human leishmaniasis (5)
Reference
1.Handman E. Leishmaniasis, current status of vaccine
development. Clin microbio. Rev 2001;4;229-43.
2.Reithinger. R, Dujardin. Jc. Louzir.H, pirme z.c., Alexander B,
Brooker S., Cutaneous leishmaniosis. Lancet. Infect.
Dis2007:7:581-96
3.Coler.R.N., Reed.s.,Second generation vaccines against
leishmeniasis Trend parasitol 2005,21:244-49
4.Genaro. O.de Toledo.v.p., Da costa.CA, Hermet mv, Afonsolc,
mayriak.w.,Vaccines for prophylaxis and immunotherapy. Brazis.
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5.Mutiso. J.M., Macharia. J.c, k;mn I
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Biomed. Res. 2013,27;85-102
6.Khalil.E.A , E.I. Hassan, A.M, Zuhystra.E.E mukhtar.
Mm.,Ghalib. HW,musa. B.et al. Autoclaved leishmania major
vaccine for prevention of visceral leishmaniasis;a randomisede
double blind, BIG-controlled trial in sudan. Lancet. 2000:356:1565-
9.
7.Khamesipour . A, Rafati.s, Davoudi.N, maboudi. F., Modabber. F.
Leishmaniasis vaccine canditate for development: A global
review.Indian. J.med. Res.2006:123:423-38.
8. Selvapandian. A, Day R., Gannavaram. S.,Lakkalvaouar. I.,
Duncan.R., Salotra, p. et al. Immunology to visceral leishmaniasis
using genetically defined live- attenuated parasite j. Trop med.
:2012:631 460
9..Palacnik-de sousa c.B., Dutra Hs, borofevic.R. Leishmania
donovani surface glyco-conjugate Gp 63 is the major immunogen
component of the fructose mannose ligand (f(ml (Act(9a. Trop.
1993:53:59-72.
10..kedzierski. I., leishmaniosis vaccine where are we today. J.Glob.
Infec. Dis 2010,2;177-85
11..Coler.Rn, Goto.y. Lisa. B, Ramen.v. Reed S.G., leish 111f, a
recombinant polyprokin vaccine that protects against visceral
leishmaniasis by elicitation of CD4+T-Cerlls.
Infect immunol. 2007:75:4648-54
12..Holder. AA.,Blackman M.J., Blackman. M.j., Burghaous.
P.Achappel. J.A., ling. IT., mcclum Deighton.N,shai. S.A. Malaria
merozoite surrface protein (MSPI). Structure, processing and
function mrm. Inst. Oswaldo ruz. 1992;87(suppl) 3;37-42
13.Chauthuri.G.,Handharm.Pan.A, changike Surface acid protionase
(gp63) of leishmania Mexicana.a metalloenzyme capable of
proteching liposome encaphlated preteins from phagolysohomal
degradation by macrophages. J. Bio. Chem.. 1989;264;7483-9
(14)Kedzicrrki. L. zhs.y. andman.E.,leishmania vaccines: progress
and problems parasitology. 2006;133. Suppl.s87-112.
(15) olobo. Jo, Anjili., co., Gichens MN et al vaccination of vervet
monkeys Cutaneous leishmaniasis using recombinant leishmania
major surface glycoprotein (gp63), vet. Paresite. 1995;60;199-212.
(16)Conell. N.D., Medina A costa E,Mcmaster wr., Bloom BR,
Rusell. DG, Effective immunization against cutaneous
leishmaniosis with recombinant bacile calmette Guerin expressing
bse leishmania surface protirase gp63 proc. Nat. acad Sci.Usa.
1993;90;11:473-7
(17)Yang.Dm, fair wcather.N. Button. Llama master wakah. I,
lpliewfy Oral salmonella typhimurium(Aroa) vaccine expressing a
major leishtimanial surface protein (gp63) pre-ferentially inducer
helper T cells and protective immunity against
leishmaniasis.J.Immanol.1990;145-2281-5
(18)Gurunathan.S.,klinman.Dm,Seder. RA
DNA vaccines immunology, application and
optimizationAnnRv. Immunol. 2000:18:927-4
19.valenzvela. J.H.,Belkaid.y, Gerfield. Mk,et al., Toward a
defined anti-leishmania vaccine targeting vector antigens.
Characterization of a protective salivary protein.J. EXP, med
2001;194;331-42.
20.Selvapandiyan.A, Dey R. Nylen. S.Duncan., sacks
D,Nakhasi.I, Intrcellular replication deficient. Leishmania
donovani induces long lasting protective immunity against
visceral leishmaniasis. J.Imman2009:183:1813-20
21.Rivier.D,Bovay.p.shah.R,Didisteim.s., masel.J .Vaccination
against leishmania major in a BA mouse model of infection. Role of
adjuvant and mechanism of protection parasite
immunol.1999:21:461-73
5. Amoebiasis vaccine
Entamoeba histolytica lives inside the larger
intestine of man. So it is an endoparasite. It
causes a disease called amoebiasis or amoebic
dysentery and also causes ulceration of colon.
Entamoeba is cosmopolitan in distribution.
There are many species of endamoeba. The
amoebic cyst is transmitted from one person to
another through the contaminated food and
water.
Amoebiasis vaccine development work is under
experimental level. Researchers identified many
antigens as serine rich binding protein N-
Acetylgalactosamine, 29 KD a cysteine –rich
protein (peroxiredoxin) lipo phaspho glycon and
oral \intranasal administration of lectins (2).
Most of the antigen efficacy studied in animal
model. Still they are not yet developed best
vaccine.(1)
Reference
1.Abhijit cha udhury (2014)Human parasite vaccines an overview –
Review. J.clin. Bio. Med. Sci. 4(1) ; 216-21.
2.Parija. Sc. Progress in the research on diagnosis and vaccines
in amoebiasis Trop. Parasitol 2011 : 1;48
6. Cestode Vaccine
6.1. Infection
Man is affected by a number of different
Cestode parasites including the Taenia solium
and T.saginata. The important worldwide
spreading Cestode are Echinococcus granulosus
and E. multiclocularis, T.Solium and T.saginata.
But incidence is considerably higher in
developing countries. {9)
6.2 Disease
The tape worm larval cyst, containing the
infective on chosphere stage is ingested with
poorly cooked infected meat. The adult may live
as long as 25 years and pass gravid proglottids,
containing eggs with the faeces. Adults establish
the intestines. The egg can persist on gestation
for several days and are consumed by cattle or
pigs in which they hatch and form cysticerci.
The eggs can also infect humans and
cause cysticercosis. Where cysts can establish in
the lungs, liver, eyes and brain resulting in
blindness and neurological disorders. Gastro
intestinal symptoms arise from the presence of
adult tape worm while cysticercosis symptoms
are due to the host inflammatory immune
responses to the parasite and abnormal
mechanical presence of the cyst (9)
6.3. Vaccine
Recombinant antigen vaccines targeting
on chosphere proteins (1) It has been developed
against infection with a number of Taenia
species including Taenia ovis in sheep (2,3).
Taenia sagninata in cattle (4) and Taenia solium
in pigs.(5, 6). These vaccines are based on groups
on chosphere proteins designated 16 k, 18 k and
45 w groups, after their original description in T.
ovis (2) Protection induced by vaccination
approaches 100%.
The 45w vaccine against Taenia ovis
infection in sheep (2) was the first highly
effective recombinant vaccine against a parasitic
infection. A similar approach was using
immuno blotting and invitro. On chosphere
killing identified a putative protective molecule
(EG 95) in Echinococcus granuloses (7). Despite
these impressive successes, these vaccines have
yet to be applied due to commercial, economic
and socio- economic reasons (1). However it
cannot be over emphasized that this work and
the work immediately below on ticks, is ground
breaking providing proof of concept for the
development of subunit vaccines against
complex metazoan parasites.
Independent vaccine trials for Taenia
solium carried out in pigs with the TSOL 18
antigen in (Transmission Blocking veterinary
vaccine) Mexico, Peru Honduras and Cameroon
have all achieved 99-100% protection. Results
were published of the first field trial of the
TSOL 18 vaccine, which was carried out in
north Cameroon. The vaccine completely
eliminated the transmission of T.solium by pigs
involved in the trial (8).
Reference
1. Light taulers. MW., Cestode vaccine, origins current status and
future prospects parasitology 2006; 133 : S 27-42.
2. Johnson K.S, Harrison G.B, Light oulers MV. Et al:
Vaccination against ovine cystice-cosis using a defined
recombinant antigen Nature, 1989 : 338: 585-7
3. Harrison. G.B. ; Health DD., Dempster.R. p et al., Identification
and CDNA cloning of two novel low molecular weight host
protective antigens from Taenia olis on cospheres. In J.Parasitol
1996 : 26: 195-204.
4. Light owlers. MW. Ralfe. R. Gauti G.G. Taenia sagninata.
Vaccination against cyliticercoses in cattle with recombinant on
cosphere antigens.Exp- parasital. 1996: 84 : 330-8.
5. Flisher A., Gakuti., C.G. Zali. A. et al., Induction of protection
against procine cysticercosis by vaccination with recombinant
on cosphere antigens Infect Immun. 2004 : 72: 5292 – 7.
6. Gonzelez. A.E., Gauc. C.G., Barbar.D. et al., Vaccination of
pigs to control human neurocysticercosis AM.J. trop.med. Hyg.
2005 : 72 : 837- 9.
7. Heath. DD., Lawrence. S.B. (1996) Antigenic polypeptides of
Echinococcus granulosus on chosphere and definition of
protective molecules, para. Immunol; 1996 ; 18 : 347-57.
8. AAskna. E, Kyngson.CT., GDauti. GG, Geerts.S Dorny.P.,
Daken.R.D.., et al., Elimination of Taenia solium transmission
to pigs in a field trial of the TSOL 18 vaccine in Cameroon. Int.
J. Parasitel.2010 ; 40 ; 515-519.
9. .Knox.D. (2010) Parasite vaccines : Recent progress in the
problems associatd with their development. The open Infec.
Disea. Jawn. 2010, 4 : 63- 73.
7. Schistosomiasis vaccine
7.1. Disease
Schistosomiasis affects an estimated 300
million people worldwide. The causative agents
are snail- transmitted, water born parasitic
helminthus. The schistosomiasis have complex
life cycle using two separate hosts to complete
their development. Severe consequence of
infection include bladder cancer or renal failure (
schistosoma haematobium) and liver fibrosis and
portal hypertension (S. mensoni). Again control
is largely dependent on mass chemotherapy but
resistance is a concern. Disease is endemic in
over 70 countries causing tens of thousands of
deaths.
S. haematobium is found in the Middle East
Africa and Southern Europe and affect the
bladder causing urinary schistosomiasis. S.
mansoni is present in most African countries
north of the equator as well as parts of central
and South America. It causes intestinal
schistosomiasis S.jalonicum is endemic in china
where bovines are the main reservoir as well as
in Indonesia and the Philippines (with dogs and
pigs reservoir) S. bovis is an important parasite
affecting cattle as well as sheep and goats a is
prevalent in south East Asia (1).
7.2 Vaccine target
The most important vaccine target of the
schistosome is the tegument. The tegument is
through to be involved in several key
physiologic processes; parasitic nutrition,
osmoregulation and the evasion of host
immunity. Tetra spanins found in outer tegument
play an important role in maintaining the
integrity of the tegument. Schistosoma mansoni;
TSP-2 has been selected by the H H V I for
development as a human vaccine antigen, (1, 2)
many proteins of the parasite may act as good
Immunogens. If identify the appropriate
Immunogens, the vaccine development process
is very easy.
7.3 Irradiated vaccine
Irradiated larval vaccine were a focus of
study in the 1970s with several early studies
being conducted in sheep challenged with S.matt
heel and S. bovis. Vaccination of mice with
radiation alternated cercariae reduced worm
burdens by 90% compared to controls and this
vaccine model has been exploited to identify the
antigens responsible for protection. The
approaches being used for vaccine development
have been extensively reviewed. (3)
7.4 Protein vaccine
Several proteins expressed on the surface of
the adult stage with particular current interest in
transmembrane proteins. Tetra spanins are
proteins which is found n the surface of karyotic
cells, including B and T cells and at least three
of these show promise as vaccine (11). SM 23 is
one of the independently tested WHO\TDR
vaccine candidates and is a testasparin expressed
in the tegument of S. Mansoni SM23 is not
effective when given as a recombinant protein
with alum but is effect when derived as a DNA
vaccine (4) There has been much focus on 26
and28 KD glutathoine –S-transferases (GSTS) .
The GSTS being though to have a detoxification
role for the parasite.
SM 28 –GST is expressed in the sub-
tegumental tissues of the parasite and
vaccination studies in rats and hamsters with the
S. hoematobium equivalent (5) indicated its
significant protective potential. Trials in
primates demonstrated and antifecundity effect
(6). Clinical testing of sh – 28 GST in people
should that the vaccine was immunogenic and
antibody inhibited the enzymatic activity of the
recombinant protein (7). A concerted effort,
based in Egypt and supported by USA, ID the
schistosomiasis vaccine development program
(SUDP), is examining two S.mansoni antigens,
parasmyosin and a synthetic peptide construct
containing multiple antigen epitopes (MAP)
from the triose phosphate isomerase.(1).
Another vaccine candidate is a 14 KD
fatty acid binding S.mansoni protein (SM 14)
which provided 67% protection against
challenge with S.Mansoni cercarioe (9) SM 14 is
a cytosolic protein expressed in a basal lamella
of the tegument and the get epithelium (8). It is an
attractive vaccine candidate because fatly acids
binding proteins play a key role in Schistosoma
nutrient acquction. Mc manus and laukas (3)
commented that an apparent efficacy ceiling of
40 to 50% was road block to success. This is
compounded by difficulties in obtaining good
expression levels and in scaling up production
according to good laboratory practice. (1)
7.5 Recombinant vaccine
The Institute pasteur has taken a
recombinant 28 KDa Glutathioe S – transferase
(GST) cloned from S.haematobium through both
phase – 1 and 2.clinical testing in Europe and
West Africa(Senegal and Niger).Sh 28 GST
(Bilhvax) is a recombinant protein formulated
with an aluminium hydroxide adjuvant. Bilhvax
appears to be immunogenic and well to be rated
healthy adults from non- endemic (France) and
S. heamatabium endemic area in Africa. The Sm
– Tsp -2 recombinant Schistosomiasis vaccine
would be intended primary for school aged
children living in the S.mansoni endemic regions
of sub – Saharan Africa and Brazil. The vaccine
ideally would prevent the real question of
schistosomiasis in the blood streams following
initial treatment with praziquantel (vaccine
linked chemotherapy) – (10).
Recently two new S. Mansoni
tetrasparin (Sm TSP -1 and Sm TSP – 2) were
identified. Recombinant TSP – 2.But not Tsp-
1,is strongly recognized by IgG and Ig G3(but
not IgE) from naturally resistant individually. It
is not recognized by IgG from chronically
infected or unexposed individuals. Both proteins
included good levels of protection in immunized
mice given an S.manloni challenge.
The authors noted that Tsp-2 in particular
provided protection in excels of etc 40% bench
mark set by the words health organization for
progression of Schistosoma vaccine antigens
into clinical trials. other antigens include a 97kd
a parasmyosin (12) and a 28kd a triose phosphate
isomerace (Tpl:eg) (9).The latter being ubiquitous
in each stage give that the S.mansoni and
S.japnicom sequences are very similar trails of
vaccine efficacy have focused on the latter with
the aim of blocking parasite transmission.(9).
7.6 Nucleic Acid Vaccine
Pigs vaccinated with a TpI DNA vaccine alone
showed reductions in adult worm burdens of
48% with female parasite being more
susceptible(13).Vaccination reduced liver egg
numbers and reduced granulomasize. Moreover,
protective immunity was stimulated in water
buffalo by vaccination with a DNA plasmid
comprising a fusion of S.jalonicum TpI,a heat
shock protein and IL-12(14).
Mc manus and Loukes (3) noted that the data
were encouraging but that extensive trails were
skill need to determine. If a vaccine of this
nature would reduce transmission as evidenced
by reduced adult worm burdens, egg outputs and
reductions in hepatic eggs. More Effective
antigens may be selected by mining the publicly
available S.mansoni and S.jalonicum
transcryptomes in combination with DNA
micro-array profiling, proteomics, glycomics
and immunomics.
The development of RNA interference
to disrupt gene function is a big step forwarded
and will enhance ability to determine the
functions of schistosome gens/proteins and it is
hoped the techniques will help define those
essential for survival and reproduction. Silencing
the expression of numerous S.mansoni genes has
resulted in phenotypic changes, highlighting
their importance as targets for vaccines and new
drugs.(15).
Reference
1.knox.Dp.parasite vaccines: :Recent progress in and problems
associated with their development. The open infectious diseases
journal.2010:4:63-73.
2.Fonesca.CT.,carvaloh GBE,Avles cc,demelo.TT.Schisistosoma
tagment proteins in vaccine and diagnosis development: An
update.J.parasitol.Res.2012;2012:541268.
3.McManus.Dp,Loukas.A.current status of vaccine for
schisitomiasis.clin.microbial.Rev.2008;21:225-42.
4.Da’dara.AA,Skelly.PJ.,Wang.M.M,Harn.DA.Immunization with
plasmid DNA encoding the integral remembrance
protein,Sm23,elicite a protective immune response against
schistasome infection in mice vaccine 2001 12.20:359-69.
5.Balloul.Jm,Grzych.Jm,piercc RJ,Capron.,A.A. ,purified 28,000
Dalton protein from Schistosoma mansoni adult worms protects
rats and mice against experimental
schistimiasis.J.Immunal.1987:138:3448-53
6 Boulange r.D.,Reid.G.D,Sturrock .Rf.et al.,Immunization of mice
and balloons with the recombinant Sm 28 GST affects both worm
viability and fecundity after experimental infection with
Schistosoma mansoni parasite Immunol.1991:13:473-90.
7 Capron.A,Riveau.G,Capron.m.,TrotteinF.Schistosomes.The road
from host parasite interactions to vaccines in clinical trails.Trends
parasite .2005:21;143-09
8 Brito.CF.oleria.Gc.,olivera sc.et.al.,sm14.gene expression in
different stages of the Schistosma mansoni life cycle and
immunolocvalization of the sm14 protein within the adult
worm.Braz.J.med.Biol,Res.2002:35:377-87.
9Harn.DA,Gu.w.olignol DMilsyana.M .Gebre
micheal,A.,Richter.D.A.protective monoclonal antibody
specifically recognized and alters the catalytic activity of
Schistosome triose phosphate isomerase.J.Immunal.1992;148:562-
7.
10.Rofatto.H.K,araujo-montoya Bo,miyasato.P.A,leavanno-
garcia.J.Rodrigue Z.D,Nakano .E etal.,Immunization with
tegurement nucleotides associated with a subcurative praziquantel
treatment reduces worm burden following schistosoma mansoni
challenge,Peer.J.2013.1:e58.
11.Tranm.H,pearson.m.S,Bethony.Jm.et al.,Tetraspanins on the
surface of schistosoma mansoni are protective antigens against
schistosomiasis.Nat.med.2006:12:835.40.
12.Pearice E J,James .Sl.Hieny.S.Lenar.De,Sher.A.Induction of
protective immunity against schistosoma mansoni by vaccination
with Schistosoma parasmyosin(sm97),a non surface parasite antigen
.proc.Nat ..Acad.Sci.USA.1988;85:5678-82.
13.Zhu.y.Si.J,Harn.DA .et al. ,Schistosoma japonicum trails
phosphate isomerase phasmid DNA vaccine protects pigs against
challenge infection.parasitology.2006;132:67-71.
14.Yu XLHe.YK,Xiong.T.et al.,Protective effects of co-
immunization with sjcTpl-Hsp70 and interleukin-12 DNA vaccines
against Schistosoma japonicum challenge infection inwater
buffalo.Z.hongguo.Ji Sheng Chong Xue Yu Ji Sheng Chong Bing
Zhi 2006,24:433-6.
15.Brindey.PJ,Pearce.EJ,Genetic manipulation of schistosomes
Int.J.Parasitol..2007,37:465-73.
8. Hook worm vaccine
8.1 Infection
Human hookworm infection is caused by the
nematode parasites Necator Americanus and
Ancylostoma duedenale infections is leading
cause of amoeba and protein malnutrition,
afflicting an estimated 740 million people in the
developing nations of the tropics. The largest
numbers of cases occur in improved rural areas
of Sub-Saharan Africa, Latin America, South
East Asia and China. N.americanus is the most
common book worm worldwide, while
A.duodenste is more geographically restricted.
Hook worm infection arises by skin contact with
infective third stage larvae (L3).
Adult hook worms are blood feeders and
attach to the mucosa of the small intestine and
cause intestinal blood loss. Typically symptoms
can arise from infections with as little as 50 to
150 of adult parasites.(1).
Infection induces as iron – deficiency
an anaemia which is indirect correlation with
the number of parasites (as measured by
quantitative egg counts).In children, chronic
hook worm infection impairs physical and
intellectual development ,reduces school
performance and attendance and adversely
affects future productivity and wage-earning
potential(1).
8.2 Disease Burden
The major human soil transmitted helmithes
(STH),Ascaris lumbricoides, Trichuris trichiura
and the hook worms occur in 1221 million,795
million and 740 million people, respectively(2)
and are among the most common pathogen of
human in developing countries. There is
considerable epidemiological overlap among
the STH infections and disability adjusted life
year (DALY) estimate indicate that the disease
burden from human STH infection is nearly
equivalent to better known Conditions such as
malaria and tuberculosis (3).They have broad
ranging effects on pregnancy, childhood
growth, nutrition and cognitive and intellectual
development.(3).
8.3. Control Measures
Control is achieved by population wide
treatment, with benzimidozole based anti
helmetics albendazole and the 2001 world
health assembly advocated the antihelmenthic
treatment of 75% of all at risk school aged
children.However,drug treatment not present
reinfection and the frequent use of drugs
required to maintain control would be likely to
lead to drug resistance. Therefore, there is a
drive to develop a safe and cost effective
vaccine.
8.4 Vaccine
The selection of the leading hook worm vaccine
candidate ,the Ancylostoma secreted protein
,ASP-2 was based on three major lines of
evidence (4).First human anti ASP-2 antibody
responses are associated with considerably
reduced risk of acquiring heavy hook worm
infection.(5).Second, when recombinant ASP-
2(expressed either in yeast or baculo virus) was
used as vaccine in animal models. it resulted in
reduction in host hookworm burden, hookworm
and fecundity(5-7).Third, anti ASP-2 antibody
inhabits larval penetration through host tissue
invitro.(5). suggesting that the vaccine elicits an
antibody response that interferes with passage
of larval through host tissue of the L3 ES
products tested,ASP-2 provided the greatest
levels of protection in canines(5) and hamster
models of hookworm infection and was
therefore given the highest priority. The most
consistent and emphatic group of protective
antigens to date identified form blood feeding
parasites are those expressed on the surface of
the gut and presumed to function in blood meal
digestion. Gut membrane proteins have been
effectively employed as vaccine antigens
against cattle ticks(8) and H.contortus (9,10) and
are offering promise as vaccine components
against hookworms .Haemoglobin digestion is
through to be facilitated by a multi-enzyme
cascade in blood feeding-parasites(11,12) and
some of the enzyme involved in this process
have been indentified in hookworms and
Haemonchus with many commonalities evident
between the two and also when compared to the
fluke and malaria parasites.
Vaccination of dogs with recombinant
AC-APR-1 significantly reduced hook worm
burdens and faecal egg counts and these dogs
were protected against blood loss and did not
develop anaemia (3) Like the AC-CP2 vaccine,
IgG from animals vaccinated with APR-1-
inhibited enzyme activity invitro and antibody
bound insitu to the intestines of worms
recovered from vaccinated dogs, implying that
the vaccine interfere with the parasite’s ability
to digest blood. This was the first report of
recombinant vaccine from a haematophagous
parasite that significantly reduced both parasite
load and blood loss, supporting the
development of APR-1 as a second arm of the
HHV.
A catalytically inactive form of homologue of
APR-1 found in Necator americanus also
induced protection against. A.caninum in dogs
.Resident in high –transmissions areas for
N.americanus had high circulating IgG to the
inactive Na-APR mutant, indicating that
natural boosting may occur in exposed
humans (13).
8.5 Hurdles In vaccine Development
A number of hurdles complicate the
development of an effective vaccine for hook
worm and for that matter other helmthics.
Some of these include
*The difficulty of maintaining human hook
worms in animal models and the cost of
maintaining hook worm in the laboratory-
canine model.
*The absence of a laboratory animal that is
permissive to human hook worms and can
accurately reproduce human
disease(anaemia).
*Paucity of invitro functional tests to
determine the efficacy of the immune
response induced by an experimental hook
worm vaccine.
*The lack of protective immune response in
humans and the consequent absence of
correlates of P.rotection that can guide the
discovery of vaccine antigens and be used to
assess their effectiveness in pre clinical and
clinical trials.
*No model of an effective immune response
in humans to determine the biological
consequences of the vaccine in humans (14).
8.6 History of vaccine Development
In 1964, Miller (15) showed that ancyloshoma
caninum larvae could be alternated
using40,000 rontgens of X.Ray. Industrial
manufacture and US licensing of the
1st,hookworm vaccine commenced in 1970s
,which consisted of gamma-irradiated
infective A.Caninum 1.3 vaccine for canine
(16).This vaccine was discontinued in 1975due
to commercial failure. Although this vaccine
failed commercially it provided compelling
evidence that human hook worm vaccine is a
possibility. The human hookworm vaccine
initiative (HHV1) is the only group currently
working in vaccines targeting this parasite.
Ancylostoma secreted protein-2 of
N.americanus (Na-ASP-2) is a 21KD a
protein, there is secreted by infective
hookworm larvae up to entry, into the host
and Na-ASp-2 was chosen as a lead
hookworm vaccine candidate (17).In phase –I
study in hookworm native adult living in the
USA,Na-ASP-2 adjuvant with alhydrogel
was well tolerated and immunogenic(18).
However, a phase I safety and
immunogenicity trial of this vaccine is
healthy adult form a hookworm endemic area
in rural Brazil. It had to be halted when 3
participants developed immediate,
generalized urticarial reactions. The urticarial
reactions were associated when elevated
levels of IgE antibodies specific for Na-ASP-
2,which were present before immunization
most likely due to previous hook worm
infection.(19).In November ,2012 Sabin
vaccine Institute an start of the part-II of its
phase –I clinical trial of the Necater
americanus –glutathione S-
transferase_1(NaGST-1) vaccine candidate
Part-II of the trial commenced in American
has brazil following successful vaccination in
part-I of the study ,which began in
belohorizonte, Brazil in late
2011.Ulternately,Na-GST-1 and Necater
americanus aspartic protease-1(Na,APR-1)
would be used together a bivalent vaccine
and the aim of the vaccine will be reduce
moderate to heavy infections in the host.(20).
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42.
16 Miller.T.A,Industrial development and field use of the
canine hook worm vaccine.Adv.parasital.1978:16333-42.
17Loukas.A.,bethony.J.Brooker.S.,Hotez.P.hookworm
vaccines:past,present and future.Lancet,Infect.Dis-2006;6:733-41.
18 Bethony.J.,Simon.G.,Diemert.DJ.,Paranti.D.,Des
rosiers.D,schuck.s.,et al.,Randomized,place controlled double-blind
trial of the Na-ASP-2 hook worm vaccine in exposed adults.Vaccine
.2008;26:2608-17.
19. Diemert.DJ.,pinto.AG.,friere.J.Jariwala.A.,santiago.H,h
amliton.RG.et al.,Generalized urticaria induced by the Na-ASP-2
hook worm vaccine: implications for the development of vaccines
against helmiths.J.Allergy.clin.Immunal.2012:130:169-76.
20. Hotez.PJ.,Diemert
D,Bacon.K.M.,beaumier.C.,Bethony.Jm,Bottazzi.ME et al.,the
human hook worm vaccine vaccine 2013;31.suppl.2:227-32.
9. Filarial Vaccine
9.1 Infection
Filarial worm (wuchereria benorefti) is a
digenic parasite. Man is the primary host and the
cluex mosquito is the secondary host. It lives in
the lymph nodes and lymph vessels of man. The
sexes are separate. The male is smaller than the
female. The male has a curved posterior end and
a pair of spicules. The male and female are
found coiled together it is viviparous, giving
birth of larvae. The larvae are called
microfilaria. It has a stylet. The microfilaria
passes from the lymph vessels into the blood
vessels.
The larva comes to the peripheral blood vessels
in the night. When the culex mosquito bites a
man containing the larva, which enters the gut of
mosquito. In the gut ,larva moults twice and
becomes another larva called filariform larva.
The filariform larva penetrates the gut and
migrates to the muscles of the mosquito. Then it
reaches the mouth parts. When the mosquito
bites another man, the larva enters the blood of
the man. It causes the obstruction of the free
flow of lymph. As a result, the lymph glands and
lymph vessels of the affected parts are enlarged.
9.2 Vaccine
To get a vaccine to eradicate the filarial disease
is still for from reach chemotherapy is the only
option left for patients (2). Still there is no vaccine
for human use. Numerous vaccine antigens are
being defined for a wide range of helminthus
parasite species, at greater understanding is
needed to develop vaccine. The vaccine
development process move to several scientific
generations such as live attenuated
organism.(Using irradiation, biochemical
fractions, recombinant protein, etc.) The
radiation –attenuated larval vaccines
successfully induced protective immunity in the
dogs and cattle. Although they were not widely
adopted(4). The use of extretory-secretory(ES-
products)were able to generate significant
immunity in animal model of Trichinella spirals
infection(5). Ansarietal.,(1) reported that highly
expressed stage specific product ALT
protein(abundant larvae transcripts) was
producing good results. It is not found in mature
adult stage. The animals immunized with ALT-1
proteins shows up to 76% reduction in parasite
survival stage specific proteins are the therefore
strong candidates for future vaccine against
human Filariasis.(3).
Refernce
1 Ansari.va,Sp.Singh,mbmjulbid,Kuldeep singh and muhamed Arif
(2016). Development of filarial vaccine by targeting stage specific
proteins.J.che.phor.res.2016;8(2);269-274.
2 Sharma.B.(2014).lymphatic filariasis and chemo therepetic
targets. Bietech Anal .Bioche.3:1-147.
3 Knox.DP.,Redmand.DL,Newlands.GF,et al ,The nature and
prospects for gut membrane proteins as vaccine candidates for
Haemonchus contortus and other ruminant Trichus trongyloids. .
Int.J.Parasitol.2003:33:1129-37.
4 Miller .T.A.,Vaccination against the canine hook worm
diseases.Adv.Parasital 1971.153-83.
5. Camphell C..H.The antigenic role of the excretions and secretions
of Trichinella spirallis in the production of immunity in
mice,J.parasital.1955-41:483-91.
10. Prevention and Control Methods
The following strategies are helpful to minimize
or completely eradicate parasitic infections.
*The complex life cycle of parasite should be
breakdown.
*Vector population should be controlled or
destroyed by suitable vector control programme.
*Stage specific vaccine will be developed and
mixed at appropriate level then used mixer
vaccine.
*First of all, mode of transmission should be
identified clearly then blocks will be developed
and stop the transmission process.
*Drinking water should be well boiled.
*Food stuffs and water should be protected from
house files and other insects.
*Destroy the mosquito and its larvae by using
biological control methods.
*Avoid active movements; during mosquito’s
peak time .Mosquito proof house should be
constructed. Use always mosquito nets.
*Applying the repellent on the surface of the
body. Spraying bio-pesticides in and around the
houses periodically.
*Integrated management of control is highly
useful to reduce the parasitic infection.
*Before eating, the hands should be washed
clearly. Finger nails should be clean and closely
cut.
*Fruits and vegetables should be thoroughly
washed.
*Should wearing sleeves and trousers.
*Use good food items which provide more
strength to our immune system. These food
items must be given particularly in endemic
areas and it should be given to children.
*Give immunotherapy to people who live in
dangerous area. It will reduce the disease burden
in future.
*Conduct awareness programme in schools and
other public area, it will be useful to people.
About the Author
Dr.M.Muruganandam is an
Editor of African journal of Biotechnology
and International journal of Medicine and
Biomedical Research. He is also Reviewer and
Editorial board member in Various National
and International journals. He published more
than hundred publication including ten books.
