title: Immunogenicity of recombinant Modified Vaccinia Ankara following a single or multi-dose vaccine regimen in rhesus monkeys.
abstract: Modified Vaccinia Ankara (MVA) is a replication-defective strain of vaccinia virus (VV) that is being investigated in humans as an alternative vaccine against smallpox. Understanding the parameters of a MVA vaccine regimen that can effectively enhance protective immunity will be important for clinical development. The present studies utilize cohorts of rhesus monkeys immunized with recombinant MVA (rMVA) or recombinant VV (rVV) vaccine vectors to investigate the magnitude, breadth, and durability of anti-VV immunity elicited by a single or multi-dose vaccine regimen. These data demonstrate that a single immunization with rMVA elicits weaker cellular and humoral immunity compared to a single inoculation with rVV. However, vaccine-elicited antibody responses, but not T cell responses, are significantly enhanced with repeated immunizations of rMVA. Importantly, only monkeys receiving up to four inoculations with rMVA generated neutralizing antibody (NAb) responses that were comparable in magnitude and durability to those elicited in monkeys receiving two inoculations with rVV. These data also show that the breadth of antibody responses against protein antigens associated with two antigenically distinct forms of infectious VV are similar in rMVA- and rVV-immunized monkeys. Together, these studies suggest that a multi-dose vaccine regimen utilizing up to four inoculations of MVA generates robust and durable antibody-mediated immunity comparable to that elicited by replication-competent VV.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Grandpre
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Duke-Cohan
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Ewald
authors.forename: Colleen
authors.initials: C
authors.lastname: Devoy
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Ellis L
authors.initials: EL
authors.lastname: Reinherz
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000235:genetics; D003429:Cross Reactions; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology; D005587:Fowlpox virus / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D008253:Macaca mulatta; D009500:Neutralization Tests; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D000956:Antigens, Viral; D012900:Smallpox Vaccine; D014614:Vaccines, Synthetic; D014765:Viral Vaccines