TY - JOUR
T1 - Peptide mimics as surrogate immunogens of mosquito midgut carbohydrate malaria transmission blocking targets
AU - Dinglasan, Rhoel R.
AU - Porter-Kelley, Johanna M.
AU - Alam, Uzma
AU - Azad, Abdu F.
N1 - Funding Information:
The authors would like to thank Helen Dooley for critical review of the manuscript. The work presented here is supported in part by grants from the NIAID/National Institutes of Health.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2005/4/15
Y1 - 2005/4/15
N2 - Transmission blocking vaccines (TBV) against mosquito midgut carbohydrate epitopes is a promising approach to curbing the spread of malaria. However, carbohydrates as immunogens can be problematic. Via the malaria transmission blocking monoclonal antibody, MG96, we isolated dodecapeptide mimics of the conserved, nominal mosquito carbohydrate epitope from a peptide-display library. Two peptide clones, bearing a constrained, consensus motif competitively inhibited MG96 reactivity with its nominal midgut microvillar antigen. However, rabbit polyclonal antisera against these synthetic peptides recognized heterologous mosquito midgut carbohydrate and protein epitopes along the midgut basal lamina. Consequently, antisera did not block parasite development within the mosquito vector. Therefore, it is imperative that peptides not only need to be functional mimics but also complete mimotopes to effectively direct the vertebrate immune response towards the nominal, protective carbohydrate epitope on mosquito microvilli.
AB - Transmission blocking vaccines (TBV) against mosquito midgut carbohydrate epitopes is a promising approach to curbing the spread of malaria. However, carbohydrates as immunogens can be problematic. Via the malaria transmission blocking monoclonal antibody, MG96, we isolated dodecapeptide mimics of the conserved, nominal mosquito carbohydrate epitope from a peptide-display library. Two peptide clones, bearing a constrained, consensus motif competitively inhibited MG96 reactivity with its nominal midgut microvillar antigen. However, rabbit polyclonal antisera against these synthetic peptides recognized heterologous mosquito midgut carbohydrate and protein epitopes along the midgut basal lamina. Consequently, antisera did not block parasite development within the mosquito vector. Therefore, it is imperative that peptides not only need to be functional mimics but also complete mimotopes to effectively direct the vertebrate immune response towards the nominal, protective carbohydrate epitope on mosquito microvilli.
KW - Carbohydrate-mimic
KW - Malaria
KW - Transmission blocking vaccine
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U2 - 10.1016/j.vaccine.2004.11.063
DO - 10.1016/j.vaccine.2004.11.063
M3 - Article
C2 - 15780718
AN - SCOPUS:15044361492
SN - 0264-410X
VL - 23
SP - 2717
EP - 2724
JO - Vaccine
JF - Vaccine
IS - 21
ER -