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Paper of the Month January 2011

Highly effective generic adjuvant systems for orphan or poverty-related vaccines

Vaccine, 29(5):873-7

Authors

Rao M, Peachman KK, Li Q, Matyas GR, Shivachandra SB, Borschel R, Morthole VI, Fernandez-Prada C, Alving CR, Rao VB

Abstract

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.