Development of Nonaggregating Poly-A Tailed Immunostimulatory A/D Type CpG Oligodeoxynucleotides Applicable for Clinical Use

Immunostimulatory cpg odns have been developed and utilized as tlr9-dependent innate immune activators and vaccine adjuvants. four different types of immunostimulatory cpg odns (a/d,b/k,c,and p type) have been reported. a/d type odns are characterized by high ifn- production but intrinsically form aggregates,hindering its good manufacturing practice grade preparation. in this study,we developed several d35-derived odns (a commonly used a/d type odn),which were modified with the addition of a phosphorothioate polynucleotide tail (such as das40),and examined their physical properties,solubility in saline,immunostimulatory activity on human pbmcs,and vaccine adjuvant potential in monkeys. we found that two modified odns including d35-das40 and d35core-das40 were immunostimulatory,similar to original d35 in human pbmcs,resulting in high ifn- secretion in a dose-dependent manner. physical property analysis by dynamic light scattering revealed that both d35-das40 and d35core-das40 did not form aggregates in saline,which is currently impossible for the original d35. furthermore,d35-das40 and d35core-das40 worked as better vaccine adjuvant in monkeys. these results suggested that d35-das40 and d35core-das40 are two promising prototypes of nonaggregating a/d type odn with advantages of ease of drug preparation for clinical applications as vaccine adjuvants or ifn- inducing immunomodifiers. © 2015 taiki aoshi et al.