title: Dose-dependent inhibition of Gag cellular immunity by Env in SIV/HIV DNA vaccinated macaques.
abstract: The induction of a balanced immune response targeting the major structural proteins, Gag and Env of HIV, is important for the development of an efficacious vaccine. The use of DNA plasmids expressing different antigens offers the opportunity to test in a controlled manner the influence of different vaccine components on the magnitude and distribution of the vaccine-induced cellular and humoral immune responses. Here, we show that increasing amounts of env DNA results in greatly enhanced Env antibody titers without significantly affecting the levels of anti-Env cellular immune responses. Co-immunization with Env protein further increased antibody levels, indicating that vaccination with DNA only is not sufficient for eliciting maximal humoral responses against Env. In contrast, under high env:gag DNA plasmid ratio, the development of Gag cellular responses was significantly reduced by either SIV or HIV Env, whereas Gag humoral responses were not affected. Our data indicate that a balanced ratio of the 2 key HIV/SIV vaccine components, Gag and Env, is important to avoid immunological interference and to achieve both maximal humoral responses against Env to prevent virus acquisition and maximal cytotoxic T cell responses against Gag to prevent virus spread.
authors.affiliation: a Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute at Frederick ; Frederick , MD USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.forename: Jinyao
authors.initials: J
authors.lastname: Li
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.forename: Viraj
authors.initials: V
authors.lastname: Kulkarni
authors.forename: Vainav
authors.initials: V
authors.lastname: Patel
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jalah
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.forename: Steven
authors.initials: S
authors.lastname: Reed
authors.forename: Niranjan
authors.initials: N
authors.lastname: Sardesai
authors.forename: Ira
authors.initials: I
authors.lastname: Berkower
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D015686:Gene Products, env / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D007111:Immunity, Cellular; D008251:Macaca; D010957:Plasmids; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D018449:SAIDS Vaccines; D019444:Vaccines, DNA
keywords: DNA electroporation; EP, electroporation; HIV vaccines; IFN-γ, interferon gamma; IM, intramuscular; bAb, binding antibody; cellular immunity; humoral immunity; vaccine optimization