title: Coadministration of cidofovir and smallpox vaccine reduced vaccination side effects but interfered with vaccine-elicited immune responses and immunity to monkeypox.
abstract: While the smallpox vaccine, Dryvax or Dryvax-derived ACAM2000, holds potential for public immunization against the spread of smallpox by bioterror, there is serious concern about Dryvax-mediated side effects. Here, we report that a single-dose vaccination regimen comprised of Dryvax and an antiviral agent, cidofovir, could reduce vaccinia viral loads after vaccination and significantly control Dryvax vaccination side effects. However, coadministration of cidofovir and Dryvax also reduced vaccine-elicited immune responses of antibody and T effector cells despite the fact that the reduced priming could be boosted as a recall response after monkeypox virus challenge. Evaluations of four different aspects of vaccine efficacy showed that coadministration of cidofovir and Dryvax compromised the Dryvax-induced immunity against monkeypox, although the covaccinated monkeys exhibited measurable protection against monkeypox compared to that of naïve controls. Thus, the single-dose coadministration of cidofovir and Dryvax effectively controlled vaccination side effects but significantly compromised vaccine-elicited immune responses and vaccine-induced immunity to monkeypox.
authors.affiliation: Department of Immunology and Microbiology, Center for Primate Biomedical Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: Huiyong
authors.initials: H
authors.lastname: Wei
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Jeff
authors.initials: J
authors.lastname: Fortman
authors.forename: Richard
authors.initials: R
authors.lastname: Wang
authors.forename: Linyun
authors.initials: L
authors.lastname: Shao
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000008:administration & dosage*; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004344:Drug Incompatibility; D008252:Macaca fascicularis; D045908:Mpox, Monkeypox / Q000517:prevention & control*; D063065:Organophosphonates / Q000008:administration & dosage*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014615:Vaccinia / Q000517:prevention & control*
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; C078786:DryVax vaccine; D063065:Organophosphonates; D012900:Smallpox Vaccine; D003596:Cytosine; D000077404:Cidofovir