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.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

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.

AIDS Res Hum Retroviruses. 1997 Sep 20;13(14):1187-94. Unique Identifier : AIDSLINE /MED97454210
Wu S; Pascual DW; Lewis GK; Hone DM; Division of Infectious Diseases and Gastroenterology, School of; Medicine, Johns Hopkins University, Baltimore, Maryland 21202, USA.

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.

Keywords: *Genetic Vectors/ADMINISTRATION & DOSAGE *Genetic Vectors/IMMUNOLOGY *HIV/GENETICS *HIV/IMMUNOLOGY *HIV Envelope Protein gp120/IMMUNOLOGY *Immunity, Mucosal/IMMUNOLOGY *Salmonella typhimurium/GENETICS *Salmonella typhimurium/IMMUNOLOGY
980130
M9811036

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