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| ISV Paper of the Month |
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January 2011 |
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Highly effective generic adjuvant systems for
orphan or poverty-related vaccines |
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Rao M, Peachman KK, Li Q, Matyas GR, Shivachandra SB,
Borschel R, Morthole VI, Fernandez-Prada C, Alving CR, Rao VB |
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Vaccine, 29(5):873-7 |
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One of the most difficult challenges in vaccine development
is the process of adjuvant selection. In addition to potency, the adjuvant must
be safe, optimize the immune response, contain easily available materials, and be
relatively inexpensive and easy to manufacture. One approach in the past has been
to compare multiple adjuvant systems for safety and potency in small animal models
but their predictive value is often poor and might even conflict with data from
human trials. In this study we examined a new algorithm in which seven adjuvant
systems were compared for efficacy and potency using a single antigen, the protective
antigen from Bacillus anthracis, in nonhuman primates (NHPs). We selected the formulations
that are generic, easy to manufacture, likely to be safe, and might be useful for
development of vaccines against difficult, neglected, or infrequent diseases. We
found that the most successful adjuvant systems were those that included liposomes
containing generic monophosphoryl lipid A (MPLA). In fact, the formulation that
elicited the highest antigen-specific and lethal toxin neutralizing titers reported
to date was the one in which liposomes containing generic MPLA were simply mixed
with the antigen. This study shows that the NHP model is attractive as a primary
alternative to small animal models to select new and superior adjuvants and that
the generic liposomal MPLA adjuvant system might be safely and easily employed with
numerous human vaccine formulations. |
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