title: Recombinant modified vaccinia virus Ankara provides durable protection against disease caused by an immunodeficiency virus as well as long-term immunity to an orthopoxvirus in a non-human primate.
abstract: Recombinant and non-recombinant modified vaccinia virus Ankara (MVA) strains are currently in clinical trials as human immunodeficiency virus-1 (HIV) and attenuated smallpox vaccines, respectively. Here we tested the ability of a recombinant MVA delivered by alternative needle-free routes (intramuscular, intradermal, or into the palatine tonsil) to protect against immunodeficiency and orthopoxvirus diseases in a non-human primate model. Rhesus macaques were immunized twice 1 month apart with MVA expressing 5 genes from a pathogenic simian human immunodeficiency virus (SHIV)/89.6P and challenged intrarectally 9 months later with the pathogenic SHIV/89.6P and intravenously 2.7 years later with monkeypox virus. Irrespective of the route of vaccine delivery, binding and neutralizing antibodies and CD8 responses to SHIV and orthopoxvirus proteins were induced and the monkeys were successively protected against the diseases caused by the challenge viruses in unimmunized controls as determined by viral loads and clinical signs. These non-human primate studies support the clinical testing of recombinant MVA as an HIV vaccine and further demonstrate that MVA can provide long-term poxvirus immunity, essential for use as an alternative smallpox vaccine.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 33, Room 1E19, 33 North Drive, MSC 3210, Bethesda, MD 20892, USA. pearl@niaid.nih.gov
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Americo
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wyatt
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Eller
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Russ
authors.initials: R
authors.lastname: Byrum
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
authors.forename: John W
authors.initials: JW
authors.lastname: Huggins
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
mesh_terms: D016915:AIDS Vaccines; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018155:Orthopoxvirus; D011213:Poxviridae Infections / Q000276:immunology / Q000662:veterinary*; D018419:Primate Diseases / Q000276:immunology* / Q000821:virology; D011323:Primates; D011994:Recombinant Proteins / Q000627:therapeutic use; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: D016915:AIDS Vaccines; D011994:Recombinant Proteins; D014764:Viral Proteins; D014765:Viral Vaccines