Evaluation of cholera vaccine candidates vcusm2 (0139), vcusm4 (el tor) and its bivalent vaccine formulation
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Date
2008
Authors
Sinniah, Kurunathan
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Abstract
Cholera has been implicated in many parts of the worlds and two serogroup identified for
causing epidemic cholera are the V cho/erae 01 and V cholerae 0139. Sharp increase of
cholera cases and deaths in 2006 showed potential of V cholerae to cause more sever~
damages and must not taken lightly. Better understanding of V cholerae as non-invasive
organism and oral route vaccination can optimally induce intestinal immune response has
led to the preference of oral cholera vaccine over parenteral cholera vaccine. Vast
majority of vaccine created were directed against 01 serogro4p only. Since cross
protection cannot be established between 01 and 0139 serogroup there is need for
bivalent vaccine for cholera. In this study we attempted to formulate a bivalent vaccine
capable of protecting against V cholerae 01 and V cholerae 0139. A bivalent vaccine
composed of auxotrophic VCUSM2 and VCUSM4 previously developed was evaluated
for immunogenicity, reactogenicity, safety and protective ability as well as their
characteristic similarities to their respective parent strain. VCUSM2 and VCUSM4 were
created by hemA mutation making them dependent on amino levulinic acid (ALA) for
survival. When supplemented with optimal ALA VCUSM vaccine strains
characteristically similar to parent strains but not in absence of ALA. In the absence of
ALA, VCUSM vaccine strains showed weakened characteristics. Auxotrophic strains
development focused on retaining characteristic features of wild types but attenuated in
term of survival abilities. VCUSM2 and VCUSM4 had limited survival capabilities in
various environmental waters. VCUSM2 and VCUSM4 did not cause diarrhea when
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tested in rabbit models when compared with virulent wild type V. cholerae. Bivalent
vaccine elicited immune response against both serogroups. Protection studies using high
dose of virulent of either wild types showed complete protection in rabbits vaccinated
with bivalent vaccine. Bivalent vaccine showed promising result in term of safety,
immunogenicity, side effects and protective capabilities and can be used against both 01
and 0139 serogroups of V. cholerae.
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Keywords
Cholera vaccine , Vaccine formulation