title: Adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges.
abstract: Recombinant proteins are being evaluated as smallpox and monkeypox vaccines because of their perceived safety compared to live vaccinia virus. Previously, we demonstrated that three or more injections of a Ribi-type adjuvant with a combination of three proteins from the outer membranes of intracellular (L1 protein) and extracellular (A33 and B5 proteins) forms of vaccinia virus protected mice against a lethal intranasal challenge with vaccinia virus. Here, we compared several adjuvants and found that QS-21 and to a lesser extent alum+CpG oligodeoxynucleotides accelerated and enhanced neutralizing antibody responses to a mixture of L1 and A33 proteins, provided the highest ratio of IgG2a to IgG1 isotype response, and protected mice against disease and death after only two immunizations 3 weeks apart. In addition, monkeys immunized with recombinant vaccinia virus proteins and QS-21 developed neutralizing antibody to monkeypox virus and had reduced virus load, skin lesions, and morbidity compared to the non-immunized group following monkeypox virus challenge.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Christiana N
authors.initials: CN
authors.lastname: Fogg
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Americo
authors.forename: Shlomo
authors.initials: S
authors.lastname: Lustig
authors.forename: John W
authors.initials: JW
authors.lastname: Huggins
authors.forename: Scott K
authors.initials: SK
authors.lastname: Smith
authors.forename: Inger
authors.initials: I
authors.lastname: Damon
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Resch
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D008993:Monkeypox virus / Q000276:immunology; D009841:Oligonucleotides / Q000276:immunology / Q000494:pharmacology*; D018155:Orthopoxvirus / Q000276:immunology*; D011213:Poxviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D012503:Saponins / Q000276:immunology / Q000494:pharmacology*; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control; D014616:Vaccinia virus / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D009841:Oligonucleotides; D011994:Recombinant Proteins; D012503:Saponins; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C041524:aluminum sulfate; C078785:saponin QA-21V1