IMMUNE-RESPONSE TO A HEPATITIS-B DNA VACCINE IN AOTUS MONKEYS - A COMPARISON OF VACCINE FORMULATION, ROUTE, AND METHOD OF ADMINISTRATION

Background: Attempts to optimize DNA vaccines in mice include using di fferent routes of administration and different formulations. It may be more relevant to human use to carry such studies out in nonhuman prim ates. Here we compare different approaches to delivery of a DNA vaccin e against the hepatitis B virus (HBV) in Aotus monkeys. Materials and Methods: Thirty-two adult Aotus l. lemurinus monkeys divided into 8 gr oups of four were immunized with 400 mu g of a DNA vaccine which encod ed hepatitis B surface antigen (HBsAg). DNA in saline was administered by intradermal (ID) or intramuscular (IM) injection with needle and s yringe, LM injection with the Biojector(R) needleless injection system or combined ID (needle) and IM (Biojebor). DNA formulated with cation ic liposomes (CellFECTIN)(R) was injected IM with needle or Biojector. DNA with added E. coli DNA (100 mu g) was injected IM with the Biojec tor or ID. A ninth group of 4 monkeys was injected LM (needle) with En gerix-B, a commercial vaccine containing recombinant HBsAg (10 mu g) a dsorbed onto alum. Monkeys were boosted in an identical fashion to the ir prime at 8 weeks, but all received the protein vaccine (Engerix-B) at 16 weeks. Sera was assessed for antibodies against HBsAg (anti-HBs) by enzyme-linked imunosorbent assay (ELISA). Results: The primary hum oral response induced by IM delivery of the DNA vaccine was very poor. In most cases there was no detectable anti-HBs even after 2 DNA doses but the kinetics of the response to subsequent protein indicated that a memory B cell response had been induced. In contrast, following IM- administration of DNA using the Biojector, detectable anti-HBs were ob served in 3 of 8 animals and evidence for immunological priming was ap parent in an additional 4 of the 8 monkeys. ID injection of DNA vaccin e in saline induced a potent antibody response which was augmented 6-f old by the addition of E. coli DNA. Combining ID and IM administration did not improve humoral immunity over ID injection alone. Conclusions : For immunization of primates with DNA vaccines, ID may be a preferab le route to LM, although it is not clear whether the Aotus monkey is a relevant model for humans in this respect. Nevertheless, the use of t he Biojector needleless injection system may improve responses with IM delivery of DNA vaccines. As well, the immunostimulatory action of E. coli DNA may be used to augment the humoral response induced by a DNA vaccine.