Human Antibody Responses to the Polyclonal Dryvax Vaccine for Smallpox Prevention Can Be Distinguished from Responses to the Monoclonal Replacement Vaccine ACAM2000

Abstract

) is representative of the vaccinia virus preparations that were previously used for preventing smallpox. While Dryvax was highly effective, the national supply stocks were depleted, and there were manufacturing concerns regarding sterility and the clonal heterogeneity of the vaccine. ACAM2000 (Acambis, Inc./Sanofi-Pasteur Biologics Co., Cambridge, MA), a single-plaque-purified vaccinia virus derivative of Dryvax, recently replaced the polyclonal smallpox vaccine for use in the United States. A substantial amount of sequence heterogeneity exists within the polyclonal proteome of Dryvax, including proteins that are missing from ACAM2000. Reasoning that a detailed comparison of antibody responses to the polyclonal and monoclonal vaccines may be useful for identifying unique properties of each antibody response, we utilized a protein microarray comprised of approximately 94% of the vaccinia poxvirus proteome (245 proteins) to measure protein-specific antibody responses of 71 individuals receiving a single vaccination with ACAM2000 or Dryvax. We observed robust antibody responses to 21 poxvirus proteins in vaccinated individuals, including 11 proteins that distinguished Dryvax responses from ACAM2000. Analysis of protein sequences from Dryvax clones revealed amino acid level differences in these 11 antigenic proteins and suggested that sequence variation and clonal heterogeneity may contribute to the observed differences between Dryvax and ACAM2000 antibody responses.

Monkeypox: disease epidemiology, host immunity and clinical interventions

“…In both vaccination groups, VACV-specific CD8 + T cells were observed to secrete IFNγ, TNF, IL-2 and CCL4 following stimulation 178 . Moreover, both ACAM2000 and Dryvax also triggered the production of VACV-neutralizing antibodies in the vaccinees 177 , 179 , despite apparent differences in the viral proteins being targeted 179 .…”

Defending against smallpox: a focus on vaccines

“…Antibodies induced by ACAM2000 have epitope profiles distinguishable from antibodies induced by Dryvax, likely due to the monoclonal nature of the ACAM2000 VACV strain relative to the highly polyclonal Dryvax [108,109]. The safety profile in humans has been shown to be similar to that of Dryvax in terms of cardiac and other AEs, though careful prescreening avoided most serious AEs [107].…”

Serum biomarkers of Burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses

“…A microarray comprised of approximately 300 recombinant proteins from B. mallei , including GroEL as well as control proteins from the gram-negative pathogen Yersinia pestis , was used to measure serological immune responses to infection. The recombinant proteins were printed in 120 μm microarray spots on slides coated with a thin layer of nitrocellulose, and antibody interactions with the immobilized antigens were measured (Figure 7 A) using previously described methods [ 19 , 20 ]. We observed that Chlorocebus aethiops monkeys infected with B. mallei exhibited a 10–100 fold increase in antibodies specific to GroEL compared to antibody responses against the control proteins y1030 and y1025 from Y. pestis (Figure 7 B).…”