title: Correlation of immunogenicities and in vitro expression levels of recombinant modified vaccinia virus Ankara HIV vaccines.
abstract: The purpose of the present study was to correlate the in vitro level of HIV Env expression by recombinant modified vaccinia virus Ankara (rMVA) with immunogenicity in mice. A 5-fold difference in Env synthesis was achieved at the translational level by the presence or absence of an out-of-frame initiation codon upstream of the env gene. This perturbation had no effect on the size or processing of Env. In contrast to the variation in Env synthesis, the rMVAs produced similar amounts of HIV Gag, which were expressed from identical cassettes. Mice immunized with the higher Env expressing rMVAs had about 15-fold higher titers of Env antibodies and several fold higher frequencies of Env-specific CD8+ and CD4+ T cells than mice immunized with the low expresser. The greater immune response achieved by high expression was maintained over a 100-fold dose range. Importantly, enhanced Env immune responses did not come at the expense of lower Gag T cell responses. These data suggest that for high immunogenicity, rMVAs should be engineered to produce the most recombinant protein that can be achieved without compromising the growth and stability of the rMVA.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892-3210, USA. lwyatt@niaid.nih.gov
authors.forename: Linda S
authors.initials: LS
authors.lastname: Wyatt
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vogt
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Eller
authors.forename: Dev
authors.initials: D
authors.lastname: Chandran
authors.forename: Jinyan
authors.initials: J
authors.lastname: Liu
authors.forename: Harriet L
authors.initials: HL
authors.lastname: Robinson
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D011995:Recombination, Genetic; D013154:Spleen / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015483:HIV Antibodies; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus