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Schistosome Vaccine -Current Candidates

 

Vaccine Candidates: The following table shows 6 antigens marked for vaccine study by WHO

(adapted from Lebens et al. )

Antigen type

Molecular size (kDa)

Stage of target

Function

% Protection in mice

Legal status

Origin

Stage of Development

Glutathione-S-transferase (Sm28GST)

28

All stages

Enzyme

30-60

Patented

Inst. Pasteur
France

Phase II trials

Paramyosin (Sm97)

97

Somula adult

Muscle protein

30

Public domain

Cornell/
CWRU/USA

GAM production

Irradiated vaccine no.5 (IrV-5)

62

All stages

Muscle protein

50-70

Patented

Johns Hopkins School of medicine/USA

DNA vaccine preparation

Triose phosphate isomerase (MAP-4)

28

All stages

Synthetic peptide

30-40

Public domain

Harvard School of Public Health/USA

Scale-up of production

Membrane antigen Sm23 (MAP-3)

23

All stages

Synthetic peptide

40-50

Public domain

Johns Hopkins/Harvard

DNA vaccine preparation

Fatty acid binding protein (FABP)
(Sm14)

14

Somula

Membrane antigen

65

Patented

Oswaldo Cruz Foundation/Brazil

GMP production

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

CWRU: Case Western Reserve University; GMP: Good Manufacturing Practice; MAP: Multi-antigen peptide; NIAID: National Institutes of Allergy and Infectious Diseases; WHO: The World Health Organization.

 

MORE INFORMATION ON SOME IMPORTANT ANTIGENS

Glutathione-S-transferase (GST), is an enzyme that was initially characterized from a c-DNA library from S.mansoni hence the name Sm28GST. The genome of this particular protein has been sequenced and research has also focused on the 3-D elucidation of the molecule. In addition, GST family is known experimentally and now at the phase II clinical trial. GST family is thought to be implicated in prostaglandin biosynthesis, which is also involved in immune response mechanism. The protective nature of GST is due to their ability to neutralize hydroperoxide, a chemical produced due to attack on tegument parasite. The 26- and 28-Kda molecules with different isoforms are well studied. The vaccine from GST kills the production of eggs and it is thought to act as anti-fecundity. Another important molecule for vaccine candidacy is Paramyosin.  Paramyosin of schistosomes is usually described as an immunogenic antigen which is involved  in most of the infected hosts (Pearce et al. 1988). After being discovered as part of the invertebrate structural muscle protein, different researchers have focused on manipulating this tegument of schistosome for vaccine development.   According to a WHO report the Schistosomiasis Vaccine Development Programme (SVDP), based in Egypt and supported by USAID, has focused on two S. mansoni antigens: paramyosin and a synthetic peptide construct containing multiple antigen epitopes (MAP) from the triose phosphate isomerase (Bachem Company, USA).  Companies like FIOCRUZ (Brazil) have also embarked on advancing the work on other vaccine candidates including Sm14, a 14 kD fatty acid-binding S. mansoni protein with cross-reactivity with Fasciola hepatica. Further studies on mice showed about 67% protection against challenge with S. mansoni cercariae.  Thus it is clear that parasite based antigens are just one of the ways that vaccines can be developed. However, due to cross-reactivity and the low efficacy approach, other more promising alternative like DNA vaccines are gaining momentum.