title: Induction of mucosal and systemic responses against human immunodeficiency virus type 1 glycoprotein 120 in mice after oral immunization with a single dose of a Salmonella-HIV vector.
abstract: Previous studies from our group showed that a Salmonella-HIV vector vaccine that expressed recombinant HIV-1 envelope protein gp120 stably in the vector cytoplasm elicited type 1 helper T cell (Th1) responses to gp120. Despite the promise of such vaccines, a major limitation in their use was that multiple immunizations were required to elicit even small responses. For this reason, we sought a modified vector configuration that would induce more potent gp120-specific T cell responses exhibiting a broader spectrum of effector functions after a single inoculation. In this article we describe the construction and immunogenicity of a Salmonella-HIV vector that displays a truncated derivative of HIV-1(IIIB) envelope in the periplasm of the vector. A single oral dose of this Salmonella vector, called H683(pW58-asd+), generated a gp120-specific proliferation response in the spleen 14 days after immunization. In agreement with our previous findings, the gp120-specific splenic CD4+ T cells elicited by H683(pW58-asd+) displayed a Th1 phenotype; however, gp120-specific splenic CD4+ Th2 cells were also evident. In addition, this strain induced strong gp120-specific IgA antibody-secreting cell (ASC) responses in the intestinal lamina propria and mesenteric lymph nodes. As many as 2% of the total lamina propria and mesenteric lymph node IgA ASCs were found to be specific for gp120 28 days after a single oral dose of H683(pW57-asd+). Because the proliferative response following a single dose of H683(pW58-asd+) was comparable to that seen previously after three doses of an analogous construct expressing recombinant gp120 in the cytoplasm, these observations suggest that Salmonella-vectored secreted HIV-1 antigens elicit higher T cell responses than their cytoplasmically bound analogs.
authors.affiliation: Division of Infectious Diseases and Gastroenterology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21202, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: D W
authors.initials: DW
authors.lastname: Pascual
authors.forename: G K
authors.initials: GK
authors.lastname: Lewis
authors.forename: D M
authors.initials: DM
authors.lastname: Hone
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003001:Cloning, Molecular; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000276:immunology*; D006678:HIV / Q000235:genetics* / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins