A proteome-wide comparison of human antibody responses to the standard polyclonal vaccine for smallpox prevention and the monoclonal replacement ACAM2000 (P4321)

Abstract

Smallpox was eradicated in the 1980s due to the success of vaccines such as Dryvax (Wyeth Laboratories, Inc., U.S.). However, production of an improved live-virus vaccine was needed due to the limited amount of Dryvax doses available, as well as manufacturing concerns over the sterility and the clonal heterogeneity of the vaccine. Clones isolated from Dryvax produce variable numbers of antigens important for protective immunity or contributing to reactogenicity. In 2008, ACAM2000 (Acambis, Inc™), a single-plaque-purified vaccinia virus derivative of Dryvax, replaced the first-generation, polyclonal smallpox vaccine. We examined human responses to Dryvax and ACAM2000 by using a protein microarray comprised of approximately 90% of the poxvirus proteome (245 proteins) to measure protein-specific IgG in sera of 71 individuals responding to a single vaccination. We observed robust antibody responses to 21 poxvirus proteins in recipients of either product (p-value ≤0.0002), while other protein antigens could be used to distinguish vaccination with Dryvax from antibody responses to the monoclonal vaccine.