G-399. Safety and Immunogenicity of an Alphavirus Replicon Vaccine for Cytomegalovirus (CMV) in Healthy Adults
Session: Poster Session: Vaccines for Adults
Saturday, October 25, 2008: 12:00 AM
Room: Hall C
Background: Development of a CMV vaccine remains a high priority because of the important role of CMV in congenital infections and infections of the immunocompromised. AVX601 is a novel CMV vaccine that utilizes an alphavirus replicon vector technology to deliver CMV proteins that are targets of humoral and cellular immunity. Methods: In this double-blind, randomized, placebo controlled, dose escalation trial, 40 healthy CMV-seronegative volunteers, 18-45 years of age, were given a low dose (LD; 1x107 infectious units) or high dose (HD; 1x108 IU ) of vaccine or saline placebo. The vaccine consists of 2 virus-like replicon particle (VRP) vectors derived from an attenuated alphavirus. One VRP component expresses the CMV glycoprotein B gene and the second expresses the pp65 and IE1 genes as a polyprotein. Subjects received LD or HD of both vaccine components or placebo in separate sites by either SC or IM inoculation, given 3 times (at months 0, 2, 6). Blood was collected following each dose and at months 9 and 12. Results: The AVX601 vaccine was well tolerated and associated with only minor local reactogenicity. While the study remains blinded for individual subjects, analysis of immune responses by group showed the vaccine to be highly immunogenic. After 3 doses, CMV neutralizing antibody was detected in 15/15 subjects (GMT 110) in the LD group and 16/16 subjects (GMT 209) in the HD group. IFNγ Elispot responses to IE1 and pp65 peptides were detected in 94-100% of subjects in LD and HD groups with a maximal mean of 504 spot forming cells per 106 PBMC for pp65 and 113 SFC for IE1. In a subset of subjects examined to date, antigen-specific multifunctional CD4+ and CD8+ T cells, expressing IFNγ, IL-2 and/or TNF-α, were induced. Conclusions: AX601 had a favorable safety profile and induced antibody and T cell responses to the 3 major immunogens of CMV. Further development of this vaccine is warranted.
A. Hoeper, RN1, D. Bernstein, MD2, E Reap3, J. Chulay3, J. Morris3, M. Maughan3, R. Olmsted3, S. Negri3 and  D. I. Bernstein,
AlphaVax Role(s): Investigator, Scientific Advisor (Review Panel or Advisory Committee), Received: Consulting Fee., (1)Cin Children's Hosp Med Center, (2)Cin Children's Hosp Med Center, Cincinnati, OH, (3)Alpha Vax Inc.

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