title: Immunogenicity and protection efficacy of subunit-based smallpox vaccines using variola major antigens.
abstract: The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on VARV antigen sequences to induce immunity against poxvirus infection.
authors.affiliation: Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Pavlo
authors.initials: P
authors.lastname: Sakhatskyy
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: Chuanyou
authors.initials: C
authors.lastname: Zhang
authors.forename: Te-Hui
authors.initials: TH
authors.lastname: Chou
authors.forename: Michael
authors.initials: M
authors.lastname: Kishko
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001835:Body Weight; D002460:Cell Line; D018890:Chemoprevention / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007668:Kidney / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017386:Sequence Homology, Amino Acid; D012899:Smallpox / Q000276:immunology / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D012901:Variola virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D014765:Viral Vaccines
chemical_list: D000956:Antigens, Viral; D007074:Immunoglobulin G; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014765:Viral Vaccines